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The Hygienic Benefits of
Antimicrobial Copper Alloy Surfaces
In Healthcare Settings
A compilation of information and data for
International Copper Association Inc.
Written by:
Al Lewis
Environmental Marketing & Communications Inc.
With editorial contributions by Ken Geremia and Ruth Danzeisen
WITHIN THE U.S., THIS DOCUMENT IS FOR INTERNAL USE ONLY BY THE
ICA, ITS MEMBERS, AFFILIATES AND THEIR MEMBERS, AND
MANUFACTURERS OF PRODUCTS MADE WITH ANTIMICROBIAL COPPER
ALLOYS
International Copper Association Inc.
260 Madison Avenue
New York, NY 10016
212-251-7240
Copperinfo.org
ii
© 2009, International Copper Association Inc.
A1335-XX/09
Printed in the USA
iii
Notice Regarding the Use of This Document in the U.S.
ONLY U.S. ENVIRONMENTAL PROTECTION AGENCY (EPA) REGISTERED
ALLOY PRODUCERS AND END-USE PRODUCT MANUFACTURERS THAT
PURCHASE EPA REGISTERED ANTIMICROBIAL COPPER ALLOYS FROM A
REGISTERED ALLOY PRODUCER ARE PERMITTED TO PROMOTE THEIR
COPPER PRODUCTS AS ANTIMICROBIAL.
This document is for scientific and academic purposes only and is not intended nor
should it be used in conjunction with the sale, marketing, or distribution of
Antimicrobial Copper Alloys within the United States. This document is intended
for internal use only by the ICA, its members, affiliates and their members, and
manufacturers of antimicrobial copper alloy products.
This document is meant to be used as background for the development of promotional
materials. Portions of the document can be used as long as the language on any resultant
marketing collateral developed is consistent with EPA product registration approvals.
THE DOCUMENT CAN BE SHARED WITH END-USE PRODUCT
MANUFACTURERS ONLY AFTER THEY’VE AGREED TO MANUFACTURE
ANTIMICROBIAL COPPER PRODUCTS. They too can use it to develop their own
marketing collateral, but they are subject to the same rules and regulations as fabricators
of copper and copper alloys.
This document includes conclusions about copper alloys that do not reflect EPA
antimicrobial public health product registration approvals. They are the opinions of
the researchers and authors and are based on their review of an extensive body of peer-
reviewed research, including preliminary studies not reviewed or approved by EPA. EPA-
approved testing to demonstrate the antimicrobial activity of copper alloys has only been
performed against the following organisms: Staphylococcus aureus, Enterobacter
aerogenes, Escherichia coli O157:H7, Pseudomonas aeruginosa and Methicillin-resistant
Staphylococcus aureus (MRSA). Any reference to effectiveness against other
organisms has not been substantiated by EPA-approved testing. Further, any
references that state or imply effectiveness in controlling disease or the transmission of
bacteria that can cause disease in humans have not been approved by either the EPA or
FDA (U.S. Food and Drug Administration). It is imperative that all marketing and
promotion of antimicrobial copper alloy surfaces in the U.S. adhere to EPA
guidelines. For locations outside of the U.S., local regulatory guidelines should be
consulted and followed.
All promotional messaging developed for use in the U.S. must clearly and prominently
state that registered copper alloys kill 99.9% within two hours, and that these claims
are based on laboratory testing when the product is cleaned regularly (to be free of
dirt or grime that can interfere with contacting the copper surface). This document
includes discussion of studies and test results showing, in some cases, effective kill rates
in time periods less than two hours. This information is provided for background
iv
purposes, but the shorter time periods should not be cited in relation to the marketing of
antimicrobial copper alloys in the U.S. Antimicrobial claims for copper alloys are
restricted, at this time, to claims of 99.9% bacterial kill within two hours.
In addition, marketing materials must contain the following language in the same font size
and prominence as any antimicrobial claims: The use of a copper alloy surface is a
supplement to and not a substitute for standard infection control practices; users
must continue to follow all current infection control practices, including those
practices related to the cleaning and disinfection of environmental surfaces. Copper
alloy surface materials have been shown to reduce microbial contamination, but they
do not necessarily prevent cross-contamination.
The Copper Development Association must review and approve all promotional materials
developed to support the sale of these products in the U.S. The CDA is committed to the
proper stewardship of antimicrobial copper alloy products and has an obligation with the
EPA to ensure that all promotional materials developed adhere to the registration and
approved label language. Please see Chapter XVI for additional information.
It is a violation of U.S. federal law to make public health claims that are inconsistent with
the approved product registration.
v
Table of Contents
Notice Regarding the Use of This Document in the U.S. ........................................... iii
Index of Tables and Figures ...........................................................................................x
I. Introduction .....................................................................................................................1
Definitions of Copper‘s Antimicrobial Action .................................................................2
II. Antimicrobial Mechanisms of Copper ..........................................................................3
Copper‘s Electrochemical Properties ................................................................................3
Molecular Mechanisms of Copper‘s Antimicrobial Action ..............................................4
III. Existing Applications for Hygienic Copper ..................................................................7
Agricultural Applications .................................................................................................7
Antifouling Surfaces and Paints........................................................................................8
Hygienic Formulations for Medical Devices ....................................................................8
Consumer Products ...........................................................................................................9
IV. Hospital-acquired Infections: Prevalence, Costs and Pressures to Reduce
Infections ...................................................................................................................11
U.S. Centers for Disease Control and Prevention (CDC) Sounds the Alarm .................11
Hospital-Acquired Infections Threaten Patient Safety ...................................................12
The Financial Burden of Hospital-acquired Infections ...................................................13
Medicare Is Changing How Hospitals Will Do Business ...............................................16
Chapter Summary ...........................................................................................................17
V. Toxic Microbes of Concern to the Healthcare Industry ............................................19
Bacteria of Concern to the Healthcare Industry: ............................................................19
MRSA: A Dangerous Threat Becomes Prevalent in Hospitals Today .......................20
Hospital-acquired MRSA Infections Have Increased Dramatically ......................20
Hand Washing, Necessary but Insufficient to Control MRSA in
Neonatal Intensive Care Units ...............................................................................21
MRSA Viable for Months on Many Touch Surfaces ............................................21
Probable Reservoirs for MRSA Infection ..............................................................22
Precautionary Measures Needed to Control MRSA in Long-term Care
Facilities ............................................................................................................22
Community-acquired MRSA on the Rise ..............................................................23
Treating MRSA Is Difficult ...................................................................................23
New Antibiotics Are Not Being Developed to Combat MRSA ............................23
Vancomycin-resistant Enterococcus (VRE) ..............................................................24
E. coli O157:H7 ..........................................................................................................24
Clostridium difficile ....................................................................................................24
Acinetobacter sp. ........................................................................................................25
Klebsiella sp. and Escherichia sp. .............................................................................25
Serratia sp. .................................................................................................................26
vi
Pseudomonas sp. ........................................................................................................26
Enterobacter sp. .........................................................................................................26
Viruses of Concern to the Healthcare Industry: ..............................................................26
Influenza .....................................................................................................................26
Rotavirus and Norovirus ............................................................................................26
Hepatitis B ..................................................................................................................26
SARS-associated Coronavirus ...................................................................................26
Norwalk Virus ............................................................................................................27
Fungi of Concern to the Healthcare Industry: .................................................................27
Candida sp. .................................................................................................................27
Aspergillus sp. and Zygomycetes sp. ..........................................................................27
Chapter Summary ...........................................................................................................28
VI. The Case for Using Copper Touch Surfaces to Kill Disease-causing Bacteria
in Healthcare Facilities .............................................................................................29
Objectives of This Chapter .............................................................................................30
Hospital Surfaces and Hospital-acquired Infections .......................................................30
Antimicrobial Efficacy Experiments on Touch Materials in Hospitals ..........................33
Study Demonstrates that Routine Cleaning Is Not Enough ............................................33
Copper and Brass Doorknobs Kill Microbes in Hospitals ..............................................33
Major New Initiatives in Evaluating the Potential for Copper Alloys to Kill
Microbes in the Healthcare Environment ...................................................................34
VII. The Case for Using Copper Touch Surfaces to Kill E. coli in Healthcare
Facilities .....................................................................................................................37
Copper Alloys Kill E. coli O157:H7; Stainless Steel Does Not .....................................37
Evaluation of Antimicrobial Efficacies of Various Copper Alloys for Medical
and Housekeeping Surfaces in Healthcare Facilities ..................................................40
Results on Pure Copper Alloys ..................................................................................43
Results on Brasses ......................................................................................................43
Results on Bronzes .....................................................................................................44
Results on Copper-Nickel Alloys ...............................................................................44
Results on Copper-Nickel-Zincs ................................................................................46
Tarnishing Does Not Reduce Antimicrobial Effectiveness of Copper Against E.
coli. .............................................................................................................................47
E. coli O157:H7 Remains Viable for Weeks on Stainless Steel .....................................48
Silver Coatings Do Not Kill E. coli Bacteria ..................................................................50
Polyethylene Does Not Kill E. coli Bacteria ..................................................................51
VIII. The Case for Using Copper Touch Surfaces to Kill Methicillin-resistant
Staphylococcus aureus (MRSA) in Healthcare Facilities ......................................54
Copper Surfaces Kill Hospital-borne MRSA; Stainless Steel Does Not ........................54
The ―Irony‖ of the Iron Alloy, Stainless Steel: Cleaning is Necessary but
Insufficient Against MRSA ........................................................................................58
Combating MRSA on Touch Surfaces: Copper vs. Non-copper Proprietary
Products .....................................................................................................................58
vii
Copper Surfaces Kill Lower Concentrations of MRSA Faster .......................................59
Chapter Summary ...........................................................................................................60
IX. The Case for Using Copper Touch Surfaces to Kill Clostridium difficile in
Healthcare Facilities .................................................................................................61
Antimicrobial Efficacy of Copper and Copper Alloys Versus Clostridium
difficile .........................................................................................................................62
X. The Case for Using Copper Touch Surfaces to Kill or Inhibit Fungal
Contamination in Healthcare Facilities ..................................................................64
Antimicrobial Experiments with Various Fungi on Copper Alloys and Aluminum ......64
XI. The Case for Using Copper Touch Surfaces to Inactivate Adenovirus in
Healthcare Facilities .................................................................................................67
XII. The Case for Using Copper Touch Surfaces to Inactivate Influenza A in
Healthcare Facilities .................................................................................................69
Antimicrobial Experiments with Influenza A on Copper and Stainless Steel ................70
XIII. The Case Against Silver and Other Antimicrobial Coating Technologies as
Touch Surfaces to Combat Cross-contamination in Healthcare Facilities .........72
Silver: More Expensive than Copper; Efficacies of Antimicrobial Coating
Technologies Questionable ........................................................................................72
Antimicrobial Properties of Silver ..................................................................................72
Silver-based Antimicrobial Technologies.......................................................................73
Representative Antimicrobial Silver-containing Coating Products ................................74
New EPA Regulations Will Restrict Silver-based Nanotechnologies ............................75
Other Competing Antimicrobial Coating Technologies .................................................76
Inappropriate Testing Standard for Antimicrobial Surface Products Results in
Inflated Claims by Manufacturers ..............................................................................77
Non-copper Antimicrobial Coating Touch Surface Technologies Do Not Work in
Healthcare Environments ............................................................................................77
XIV. Dermal Effects of Copper .............................................................................................80
Copper is Essential in Maintaining and Improving Dermal Health ................................80
Dermal Contact with Copper is Not Toxic .....................................................................80
No Dermal Penetration by Copper .................................................................................81
Copper Is Not a Dermal Irritant; Dermal Hypersensitivities Extremely Rare ................81
XV. Potential for Microbial Resistance to Copper’s Antimicrobial Efficacy .................82
XVI. U.S. EPA Registration of Antimicrobial Copper Touch Surfaces ...........................84
Public Health vs. Non-Public Health Antimicrobial Claims .........................................84
Background on the Registration Process .......................................................................85
CDA‘s Leadership Role in the EPA Registration of Copper and Copper Alloys as
Antimicrobial Materials ..............................................................................................86
viii
EPA Test Protocols for Copper.......................................................................................86
GLP Laboratories Ensure Data Integrity and Accuracy .................................................87
Copper Alloys and Pathogens Evaluated for EPA ..........................................................88
Test Results .....................................................................................................................88
Results for Efficacy of Copper Alloy Surfaces as a Sanitizer ....................................88
Results for Residual Self-sanitizing Activity of Copper Alloy Surfaces ...................90
Results for Continuous Reduction of Bacterial Contamination on Copper
Alloy Surfaces ............................................................................................................90
EPA Registration of Antimicrobial Copper Alloys ........................................................92
EPA Health and Safety Assessment ...........................................................................92
Registered Copper Alloys ..........................................................................................93
Approved Label Claims ..............................................................................................93
Product Stewardship ...................................................................................................94
Chapter Summary ...........................................................................................................95
XVII. U.S. Department of Defense Funding for Antimicrobial Copper Research
and Other Hospital Trials ........................................................................................97
DoD Addresses Problem of Keeping Injured Soldiers Safe from Hospital-
acquired Infections ......................................................................................................98
DoD Takes Initiative to Clean Up Its Hospitals and Healthcare Centers .......................98
Clinical Trial #1: Copper Antimicrobial Research Program to Determine the
Efficacy of Copper Touch Surfaces to Mitigate Cross-contamination of
Infectious Disease ..................................................................................................98
Clinical Trial #2: Copper Air Quality Program .......................................................101
Other Hospital Trials throughout the World ................................................................103
United Kingdom...................................................................................................103
Japan ....................................................................................................................103
Chapter Summary .........................................................................................................103
XVIII. Market Opportunities for Copper Touch Surfaces in Healthcare Facilities.........105
Medical Equipment and Housekeeping Surfaces .........................................................105
Hospital Sanitizers and Disinfectants Do Not Affect the Performance of Copper
Alloys ............................................................................................................................108
Future Studies on Copper Alloy Surfaces as Antimicrobial Agents ............................108
Creating Awareness Amongst Stakeholders .................................................................109
XIX. Conclusions ..................................................................................................................111
APPENDIX
XX. Copper: Antimicrobial, Yet Also Essential for Humans, Animals and Plants .....113
Essentiality of Dietary Copper ......................................................................................113
Metabolic Copper Deficiency .......................................................................................114
Nutritional Requirements ..............................................................................................114
Foods Containing Copper .............................................................................................115
ix
XXI. EPA Approved Master Label for Antimicrobial Copper Alloys Group I
(April 2009) ............................................................................................................116
XXII. EPA Registered Antimicrobial Copper Alloys .........................................................123
XXIII. References ....................................................................................................................127
x
Index of Tables and Figures
Tables
6.1 Summary of hospital-acquired pathogens and environmental contamination .......................31
6.2 Ranking of contaminated surfaces in public spaces by percentage of surfaces
positive for protein and biochemical markers ..................................................................32
6.3 Target list of pathogens for antimicrobial experiments at healthcare facilities .....................35
7.1 Nominal alloy compositions (weight, %) ..............................................................................41
7.2 Elapsed time of initial bacteria count drop-off and for near-zero bacteria count ..................42
8.1 Reduction of S. aureus in zeolite powder amended with metal ions .....................................55
13.1 Log-10 MRSA reduction on copper alloys and a silver-containing coating on
stainless steel as a function of temperature and relative humidity...................................79
16.1 Nominal Copper Alloy Compositions (by elemental weight %) ...........................................88
16.2 Results of testing under three EPA test protocols demonstrate the antimicrobial
efficacy of copper alloys: efficacy as a sanitizer, residual self-sanitizing
activity, and continual reduction of bacterial contaminants ............................................89
16.3 Registered groups of antimicrobial copper alloys with their respective ranges of
copper content and EPA registration numbers.................................................................93
17.1 Target surfaces identified for hospital clinical trials in DoD-funded copper
antimicrobial surface study ..............................................................................................99
17.2 Roadmap of Clinical Trial #1 copper antimicrobial research program funded by
DoD ..................................................................................................................................102
18.1 Potential Uses of Copper Alloys for Medical Equipment .....................................................107
18.2 Potential Uses of Copper Alloys for Housekeeping Touch Surfaces ....................................107
Figures
4.1 Proportion of S. aureus nosocomial infections resistant to oxacillin (MRSA)
among intensive care unit patients, 1989–2003 ...............................................................13
7.1 E. coli O157:H7 viability on copper alloy C11000 surfaces showing an almost
complete (over 99.9%) kill of the pathogen on copper within 90 minutes at
20°C and within 270 minutes at 4°C ...............................................................................38
7.2 The Survival of Escherichia coli O157:H7 on different copper alloy surfaces at
room (top) and refrigeration temperatures .......................................................................39
7.3 E. coli O157:H7 viability on stainless steel (S30400) showing no signifciant
reduction in viable organisms after 270 minutes .............................................................40
7.4 E. coli O157:H7 Viability at 20°C and 4°C on Alloy UNS C10200 Copper
Surfaces ............................................................................................................................43
7.5 E. coli O157:H7 Viability at 20°C and 4°C on Brass Alloy UNS C22000 Surfaces ............45
7.6 E. coli O157:H7 Viability at 20°C on Surfaces of Six Bronze Alloys ..................................45
7.7 E. coli O157:H7 Viability at 20°C on Surfaces of Six Copper-Nickel Alloys ......................45
7.8 Decrease in bacterial numbers with exposure time on copper-nickel-zinc (nickel-
silver) family alloys at 20°C (top) and 4°C .....................................................................46
xi
7.9 Time at which practically no viable bacteria are detected at 20°C and 4°C on 25
copper alloys ....................................................................................................................47
7.10 E. coli O157:H7 counts on a tarnished (T) copper alloy (C19700, containing 99%
Cu) dropped by more than 99.9% within just 60 minutes at 20°C, initially
outpacing the efficacy of the clean (B) surface ...............................................................48
7.11 E. coli O157:H7 counts dropped faster initially on tarnished surfaces of copper
alloy C22000 (containing 90% Cu) than on a bright, clean surface of the same
alloy..................................................................................................................................49
7.12 E. coli O157:H7 viability on bright and tarnished alloy C19700, C22000, and
C77000 surfaces at 20°C ..................................................................................................49
7.13 Long-term viability of E. coli O157:H7 after 28 Days at 20°C and 4°C on S30400
Stainless Steel Surface .....................................................................................................50
7.14 Epifluorescent photographs of E. coli O157:H7 demonstrate that the pathogen is
completely killed (greater than 99.9% reduction) on copper alloy C10200 after
90 minutes at 20°C (b). There are a substantial number of pathogens on
stainless steel S30400 (a) after the same time interval. ...................................................51
7.15 E. coli viability at room and chill temperatures on a stainless steel surface with
Agion®-containing coating...............................................................................................52
7.16 E. coli O157:H7 viability at 20°C on surfaces of Alloy S30400 and on
Polyethylene, indicating that neither of these materials can kill the pathogen to
any significant degree within 4½–6 hours .......................................................................52
8.1 Survival times of Methicillin-resistant Staphylococcus aureus on three copper
alloys and stainless steel (S30400) at room temperature. ................................................56
8.2 Effect on MRSA viability during a 6-hour exposure to stainless steel S30400 and
copper alloys C77000, C24000 and C19700 at 4°C ........................................................57
8.3 Effects of copper vs. selection of antimicrobial coating products on MRSA at
20°C .................................................................................................................................58
8.4 The Kill Rate of Copper Alloy C11000 (99.9% copper) Related to Inoculum Size .............59
9.1 Viability of C. difficile spores and total vegetative cells on various copper alloys
and stainless steel .............................................................................................................63
10.1 A. niger spores after 7 days exposure on copper (C11000) (a) and aluminum (b);
A. flavus after 4 days exposure on copper (c) and aluminum (d); and A.
fumigatus after 4 days exposure on copper (e) and aluminum (f) assessed
using epifluorescence microscopy ...................................................................................65
10.2 Inhibition of A. niger growth on copper (a) and aluminum (b) coupons after 10
days ..................................................................................................................................66
11.1 Epifluorescent photographs show that copper inactivates 99.999% of Adenovirus
particles within six hours. On stainless steel, 50% of the infectious particles
survive within the same time period ................................................................................68
12.1 Fluorescent microscopy analysis photo of virus plates indicates a 75% reduction
of influenza A after one hour of exposure on copper, and a 99.999% reduction
of the pathogen after six hours on copper. Many organisms are still alive on
stainless steel after 24 hours ............................................................................................70
13.1 Effects of copper vs. selection of proprietary antimicrobial coating products on
MRSA at 20°C. Only copper was found to be antimicrobial against MRSA in
environments representative of those within healthcare facilities ...................................78
xii
16.1 Typical data for efficacy of copper alloy surfaces as a sanitizer on
microorganisms tested for EPA. This table illustrates results with
Staphylococcus aureus (ATCC 6538) and Enterobacter aerogenes (ATCC
13048) ..............................................................................................................................89
16.2 Residual antimicrobial efficacy of copper alloy C26000 after inoculation of
Staphylococcus aureus and Enterobacter aerogenes. Copper alloy C26000
performed just as well in the initial two hour antimicrobial efficacy test as it
did after the six wet and dry wear cycles .........................................................................90
16.3 Continuous reduction of E. coli O157:H7 on C11000 inoculated eight times over
a 24-hour period ...............................................................................................................91
16.4 Continuous reduction of MRSA on C11000 inoculated eight times over a 24-hour
period ...............................................................................................................................92
16.5 Scan of the official registration document for Antimicrobial Copper Alloys Group
II (Registration documents for the five groups are identical) ..........................................95
1
I
Introduction
Before it was recognized that microorganisms existed, the Egyptians, Greeks, Romans and
Aztecs used copper compounds for the treatment of disease and good hygiene. According
to a 4000-year-old medical text known as the Edwin Smith Papyrus, the ancient Egyptians
used copper as to clean wounds and drinking water. In 400 BC, Hippocrates, the great
Greek physician commonly referred to as the ―father of medicine,‖ treated open wounds
and skin irritations with copper. The Romans catalogued numerous medicinal uses of
copper for various diseases. The Aztecs treated sore throats and skin irritations with copper
oxide and the copper mineral malachite. The Persians and Indians used copper to treat
boils, eye infections and venereal ulcers. Interestingly, during the cholera epidemic in
1850s Paris, copper workers were found to be less affected by the disease.
In the 19th
century, after microbes were discovered and the germ theory of infection linked
bacteria and other microorganisms to infection and disease, scientists began to understand
how copper‘s antimicrobial properties could be harnessed to provide additional benefits.
Today, the antimicrobial uses of copper have been expanded to include fungicides,
antifouling paints, antimicrobial medicines, oral hygiene products, hygienic medical
devices, antiseptics and a host of other useful applications.
In this paper, copper‘s antimicrobial properties are evaluated as a potential solution to
bacterial contamination that can cause human infections in healthcare facilities (hospitals,
rehabilitation centers, long-term care facilities, nursing homes, hospices, foster and group
homes, mental institutions, etc.).
The high incidence of hospital-acquired infections in our nation‘s health-related facilities
suggests that current hygienic practices remain inadequate. U.S. Centers for Disease
Control (CDC) statistics reveal a dramatic increase in the incidence of hospital-acquired
infections during the past 20 years — despite enormous advances in understanding how
pathogenic microbes cause illnesses and deaths. Furthermore, since few prospective
antibiotics are in the pipeline to combat evolving and resistant microbe strains that
increasingly plague our healthcare system, the medical community is ill-prepared to protect
patients against these deadly pathogens.
Key scientific investigations are cited in this paper to demonstrate the efficacy of copper
and copper alloys to reduce (i.e., kill 99.9% within two hours) hospital-borne microbes,
including Methicillin-resistant Staphylococcus aureus (MRSA) — a deadly pathogen that
has become a primary concern of healthcare administrators today. The recent discovery of
copper‘s intrinsic ability to kill MRSA and other deadly pathogens holds forth the
possibility that the replacement of numerous touch surfaces with copper alloys at
healthcare facilities can be an important measure in reducing bacterial contamination on
surfaces.
2
Definitions of Copper’s Antimicrobial Action
The following definitions are applied throughout this paper when describing copper‘s effect
on microorganisms. (The definitions are adapted from Black, J.G. (1966), Microbiology:
Principles and Applications, Third Edition, Prentice Hall, pp. 332–352. Notes are not from
this text.)
Bacteriostatic/fungistatic: A ―-static‖ agent inhibits microbial growth by means other than
killing; a -static agent limits the growth of microorganisms and may inactivate them.
Antimicrobial: An ―antimicrobial‖ substance (chemical or physical) can prevent microbial
growth either by some -static action or by the outright killing of microbes.
Bactericidal/fungicidal: A ―-cidal‖ agent either damages microorganisms at low
concentrations and/or reduced contact time or interacts permanently with microorganisms
so that they cease to function normally; such agents damage microorganisms sublethally;
total inactivation is functionally equivalent to killing the organisms (0% survival).
Sanitization: Sanitization is the removal of pathogenic microorganisms from public
objects or surfaces, leading to improved hygiene.
NOTE: For a product to be approved to make ―sanitizer‖ claims, USEPA requires
that the product achieve a 3-log (99.9%) reduction within 5 minutes. Antimicrobial
Copper Alloys achieve this kill rate within two hours and, therefore, are not
registered with EPA to make ―sanitizer‖ claims.
Hygienic surface: A hygienic surface inhibits microbial growth and may totally kill certain
organisms.
Disinfection: Disinfection is the process of inhibiting or reducing the number of
pathogenic organisms on objects or in materials so that they pose no threat of disease.
NOTE: For a product to be approved to make ―disinfection‖ claims, U.S. EPA
requires that the product kill all test organisms on 59 out of 60 test samples.
Antimicrobial Copper Alloys are not registered with EPA to make ―disinfection‖
claims.
3
II
Antimicrobial Mechanisms of Copper
In this chapter, research studies regarding the effects of copper on microbes (bacteria, fungi
and viruses) are cited, and complex molecular mechanisms responsible for copper‘s actions
are introduced. These observations have prompted the recent exploration of the
antimicrobial properties of metallic copper and copper alloy surfaces in ambient and chilled
air environments for applications in healthcare facilities, as well as in food-processing
plants and heating, ventilating and air-conditioning (HVAC) systems.
It is important to note that, while copper‘s antimicrobial properties inhibit the growth of
microorganisms, copper is also an essential mineral vital to the good health of humans,
animals and plants. A discussion about the essentiality of dietary copper, the nutritional
requirements of copper, symptoms of nutritional copper deficiency, and foods that contain
adequate supplies of nutritional copper is presented in the Appendix (XX).
Copper has been shown to be an antimicrobial substance, with laboratory testing showing
that 99.9% reductions are achieved within two hours for specified bacteria. In light of
promising preliminary testing, researchers continue to examine the efficacy of copper
alloys against many species of harmful bacteria, viruses, and fungi. Currently, EPA has
approved copper alloys as effective against E. coli O157:H7, Methicillin-resistant
Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter aerogenes, and
Staphylococcus aureus. This property supports the use of copper as a hygienic surface.
Copper’s Electrochemical Properties
Copper is classified as a transition element on the Periodic Table. The structure of its outer
electron shell, specifically, the ability to readily donate or accept an electron, is the source
of many of its useful properties, including thermal and electrical conductivity and the
electrochemical properties that biological systems employ.
Elemental copper has one electron in its outer shell which can be readily removed to form
Cu+1
which is known as the cuprous ion. The second outermost shell is completely full and
is still relatively unstable. An additional electron can be removed from this shell to form
the cupric ion, or Cu+2
.
Both of these electrochemical reactions are called oxidation because electrons are lost. The
reverse reaction, in which electrons are added, is called reduction.
The oxidation state of copper in most copper compounds is +2, or Cu+2
. The cuprous ion,
Cu+1
, is very unstable in aqueous solutions and quickly oxidizes to Cu+2
.
4
Among the transition elements on the Periodic Table, copper‘s ability to donate or accept
an electron is very strong. This means that copper has a high electrochemical (oxidation-
reduction, or redox) potential.
Molecular Mechanisms of Copper’s Antimicrobial Action
For many years, scientists have been attempting to identify the precise chemical and
molecular mechanisms responsible for copper‘s antimicrobial properties. In 1973,
researchers at Battelle Columbus Laboratories (Dick, R.J. et al.,, 1973) conducted a
comprehensive literature, technology and patent search that traced the history of
understanding the ―bacteriostatic and sanitizing properties of copper and copper alloy
surfaces‖ and clearly demonstrated that copper, in very small quantities, has the power to
control a wide range of molds, fungi, algae and harmful microbes. Of the 312 citations
mentioned in the study across the time period 1892–1973, the observations below are
noteworthy:
- Copper inhibits Actinomucor elegans, Aspergillus niger, Bacterium linens, Bacillus
megaterium, Bacillus subtilis, Brevibacterium erythrogenes, Candida utilis,
Penicillium chrysogenum, Rhizopus niveus, Saccharomyces mandshuricus, and
Saccharomyces cerevisiae in concentrations above 10 g/l (Chang and Tien, 1969).
- Torulopsis utilis is completely inhibited at 0.04 g/l copper concentrations (Avakyan
and Rabotnova, 1966).
- Tubercle bacillus is inhibited by copper as simple cations or complex anions in
concentrations from 0.02 to 0.2 g/l (Feldt, no year).
- Achromobacter fischeri and Photobacterium phosphoreum growth is inhibited by
metallic copper (Johnson, Carver, Harryman, 1942).
- Paramecium caudatum cell division is reduced by copper plates placed on Petri
dish covers containing infusoria and nutrient media (Oĭvin and Zolotukhina, 1939).
- Poliovirus is inactivated within 10 minutes of exposure to copper with ascorbic acid
(Colobert, 1962).
Note: Copper alloys are not registered with U.S. EPA to make antimicrobial claims
against the above organisms.
A subsequent paper (Thurman and Gerba, 1989) probed some of copper‘s antimicrobial
mechanisms and cited no less than 120 investigations into the efficacy of copper ion action
on microbes. The authors note that the antimicrobial mechanisms are very complex and
take place in many ways, both inside cells and in the interstitial spaces between cells. They
suggest that copper has wide-ranging possibilities as an antimicrobial agent.
5
Some examples of the molecular mechanisms mentioned by Thurman and Gerba (1989)
and by other authors include the following:
- The 3-dimensional structure of proteins can be altered by copper, so they can no
longer perform their normal functions. The result is inactivation of bacteria or
viruses (Thurman and Gerba, 1989)
- Copper complexes form radicals that inactivate viruses (Kuwahara et al., 1986;
Vasudevachari and Antony, 1982).
- Copper may disrupt enzyme structure and function by binding to sulfur- or
carboxylate-containing groups and amino groups of proteins (Sterritt and Lester,
1980; Martin, 1986).
- Copper may interfere with other essential elements, such as zinc and iron
- Copper facilitates deleterious activity in superoxide radicals. Repeated redox
reactions on site-specific macromolecules generate OH- radicals, thereby causing
―multiple hit damage‖ at target sites (Samuni et al., 1983, 1984).
- Copper can interact with lipids, causing their peroxidation and opening holes in the
cell membrane, thereby compromising the integrity of the cell (Manzl et al., 2004).
This can cause leakage of essential solutes which in turn can have a desiccating
effect.
- Studies of copper‘s effect on Escherichia coli cells indicate that the respiratory
chain is at least one site of damage (Domek et al., 1984) and is associated with
impaired cellular metabolism (Domek et al., 1987).
- Faster corrosion correlates with faster inactivation of microorganisms. This may be
due to increased availability of cupric ion, Cu2+
, which is believed to be responsible
for the antimicrobial action (Michels, Wilks, Noyce, and Keevil, 2005).
- In inactivation experiments on the flu strain, H1N1, which is nearly identical to the
H5N1 avian stain and the 2009 H1N1 (swine flu), researchers hypothesized that
copper‘s antimicrobial action probably attacks the overall structure of the virus and
therefore has a broad-spectrum effect (Michels, 2006).
Note: Copper alloys are not registered with U.S. EPA to make antimicrobial claims
against H1N1 or other viruses.
Microbes use copper-containing enzymes to help drive vital chemical reactions. Excess
copper, however, can affect proteins and enzymes in microbes, thereby inhibiting their
activity and giving copper its antimicrobial characteristic. Researchers believe that copper
has the potential to disrupt cell function both inside cells and in the interstitial spaces
between cells, probably acting on the cells outer envelope (BioHealth Partnership, 2007).
6
Our current understanding is that the most important antimicrobial mechanisms for copper
include the following:
- Elevated copper levels inside a cell cause oxidative stress and the generation of
hydrogen peroxide. Under these conditions, copper participates in the so-called
Fenton-type reaction — a chemical reaction causing oxidative damage to the cell.
- Excess copper causes a decline in the membrane integrity of microbes, leading to
leakage of specific essential cell nutrients, such as potassium and glutamate. This
leads to desiccation and subsequent cell death.
- While copper is needed for many protein functions, in an excess situation (as on a
copper alloy surface), copper binds to proteins that do not require copper for their
function. This ―inappropriate‖ binding leads to loss-of-function of the protein,
and/or breakdown of the protein into nonfunctional portions.
These potential mechanisms, as well as others, are the subject of continuing study by the
International Copper Association and independent academic research laboratories around
the world.
No matter what the precise molecular mechanisms may be or how they may work in
synchrony, the point to be emphasized here is that the literature unquestionably confirms
that copper is antimicrobial in various environments.
7
III
Existing Applications for Hygienic Copper
The scientific literature cites the efficacy of copper to kill such harmful microbes as
Actinomucor elegans, Aspergillus niger, Bacterium linens, Bacillus megaterium, Bacillus
subtilis, Brevibacterium erythrogenes, Candida utilis, Candida albicans, Penicillium
chrysogenum, Rhizopus niveus, Saccharomyces mandshuricus, Saccharomyces cerevisiae,
Torulopsis utilis, Tubercle bacillus, Achromobacter fischeri, Photobacterium
phosphoreum, Paramecium caudatum, Poliovirus, Proteus, Escherichia coli,
Staphylococcus aureus and Streptococcus Group D. Existing applications for hygienic
copper are summarized in this chapter.
Please note that within the U.S., promotional materials developed to support the sale
of antimicrobial copper touch surface products can only claim antimicrobial efficacy
against E. coli O157:H7, Methicillin-resistant Staphylococcus aureus, Pseudomonas
aeruginosa, Enterobacter aerogenes, and Staphylococcus aureus, as per the EPA
registration.
Agricultural Applications
The most extensive fungicidal usage of copper compounds began, by accident, in the 1700s
with the discovery that seed grains soaked in copper sulfate inhibited seed-borne fungi.
Shortly thereafter, the steeping of cereal seeds in copper solutions became a standard
farming practice for controlling stinking smut or bunt of wheat, which was endemic
wherever wheat was grown. The practice of treating seed grains with copper sulfate was so
effective that more than a few bunted ears in a wheat field were considered a sign of
neglect by the farmer. Today, due to copper sulfate applications, this seed-borne disease is
no longer an economic problem.
In the Bordeaux district of France, the 19th
century French scientist Millardet noticed that
vines daubed with a paste of copper sulfate and lime to make the grapes unattractive to
theft appeared to be freer of downy mildew disease. This observation led to a cure (known
as the Bordeaux Mixture) for the dreaded mildew and prompted the commencement of
protective crop spraying. Trials with copper mixtures against various fungal diseases soon
revealed that many plant diseases could be prevented with small amounts of copper. Ever
since, copper fungicides have been indispensable throughout the world.
Because of its fungicidal and bactericidal properties, copper sulfate was also used on farms
as a disinfectant against storage rot and for the control and prevention of certain animal
diseases, such as foot rot in sheep and cattle. Thirty-two references describing the
fungicidal properties of copper fungicides are cited by Sagripanti (1992).
8
Modern copper formulations, such as copper-8-quinolinate, copper octoate, nanocopper
oxide, alkaline copper quat, copper azole, and ammoniacal copper arsenate are now used to
fight fungus in crops, textiles, paints, and woods (BioHealth Partnership Publication,
2007).
Antifouling Surfaces and Paints
Copper is essential in the biotechnology industry. Microbiologists and cell culture scientists
have for many years relied on copper-walled incubators to resist microbial growth,
particularly fungal growth, and to resist contamination of sensitive human and animal cell
lines when they are being cultured in humidified laboratory incubators (sources:
www.shellab.com/whitepapers/EliminatingContamination.pdf and
www.sanyobiomedical.com/products_page.php?id=MCO-17AC).
Copper‘s potent antifouling properties help control unwanted organisms from clogging
underwater mesh cages used in fish farming. The antifouling benefits of copper sheathing
on the bottom of boats and of copper-based paints for the marine environment have been
known for years. Antifouling copper-based paints are able to reduce bacterial populations
by 99.9975% within 24 hours, according to Cooney and Kuhn (1990).
Experimental work by these researchers confirmed the biocidal activity of copper on a
prototype latex formulation containing 0.25 pound of cuprous oxide per gallon. Within the
first 24 hours of contact, this formulation produced a 6–7-log reduction in all four bacterial
populations studied (Staphylococcus aureus, Streptococcus faecalis, Escherichia coli,
Pseudomonas aeruginosa). A minimum -cidal efficiency of 99.9999% was observed.
Hygienic Formulations for Medical Devices
Copper has antimicrobial applications in many different types of medical devices.
While researching hygienically sensitive materials for the medical device industry,
Sagripani (1992) discovered antimicrobial formulations for bronchoscopes. A copper
chloride solution was found to kill Bacillus subtilis with an efficacy similar to disinfectant
and sterilization chemicals typically used by the medical devices industry (BioHealth
Partnership Publication, 2007).
But, the copper formulations had significant advantages. Unlike formaldehyde (a
commonly used disinfecting agent known to be mutagenic and carcinogenic) or
glutaraldehyde (the most potent disinfectant in the medical device industry which adversely
affects more than a third of staff personnel who use it), copper solutions were considered to
be ―harmless,‖ since copper concentrations remaining on the disinfected medical devices
were expected to be below human sera levels (1.1 mg/liter).
9
The study also demonstrates that mixtures of copper and peroxide are even more efficient
than glutaraldehyde in inactivating Bacillus subtilis and Escherichia coli bacteria. The
inactivation rate of copper peroxide was found to be 4.5 to 5 times faster than
glutaraldehyde.
Zeelie and McCarthy (1998) studied the effects of copper and zinc ions on the rate of
killing of Gram-negative bacterium Pseudomonas aeruginosa, Gram-positive bacterium
Staphylococcus aureus, and fungal yeast Candida albicans by the antiseptic agents
cetylpyridinium chloride and povidone-iodine (Betadine). In 48 test cases, copper and zinc
ions clearly potentiated the antiseptic agents in 28 cases (58.3%) and exhibited an
improved activity in 15 cases (31.3%).
Consumer Products
Consumer products made with copper have been used in kitchen environments for their
antimicrobial properties for years. Copper scrubbing products help to reduce bacterial
contamination on pots and pans and copper sink strainers are commonplace in many
regions of the world, especially in Japan. In the Middle East, tabletops have been made
from copper for centuries. [Note: the USEPA registration for Antimicrobial Copper
Alloys does not allow antimicrobial claims to be made for food contact surfaces.]
Copper is also used for its bactericidal properties in medicines and hygienic products, such
as anti-plaque agents in mouthwashes and toothpastes.
Worthy of mention is a copper-based antimicrobial product that prevents slime buildup in
commercial icemakers. The daily buildup of bacteria and algae in ice machines can
compromise the hygienic quality of ice cubes and creates problems commonly cited by
restaurant and hotel managers. To combat this problem, Apyron, a U.S.-based
manufacturer of air and water purification systems, developed the IceWand™, an
antimicrobial product that is installed in ice-making machine sumps to combat daily build-
up of bacteria and algae in ice machines. Approved by NSF International under ANSI/NSF
Standard 42 material requirements and registered by the EPA as an antimicrobial agent, the
IceWand time-releases copper into the ice cube water, where it coats internal surfaces
during ice making. According to the manufacturer, the copper interferes with microbial cell
replication, electron transport and metabolic functioning, thereby mitigating slime buildup.
The manufacturer states that IceWand is used ―in environments where there are higher than
normal amounts of airborne yeast, bacteria, algae and mold. Pizza parlors or anywhere
bread is baked or beer is served are prime examples.‖ Established restaurant and hotel
chains in the U.S. that use IceWand, such as McDonald‘s and Best Western Hotels, report
that mold and slime are no longer present in holding bins, water troughs, cubers, plumbing
or tubing.
It is worth noting that IceWand customers have reported that the product has reduced
maintenance costs associated with ice making machine operations. Apyron‘s innovative
10
IceWand technology clearly demonstrates the efficacy and cost-effectiveness of copper for
antimicrobial applications in cold, moist environments.
11
IV
Hospital-acquired Infections: Prevalence, Costs and
Pressures to Reduce Infections
In the 1850s, some 30 years before scientists understood that a world of microbes was
responsible for many diseases, the highly respected English nurse, Florence Nightingale,
discovered that her patients fared much better when the hospital environment in which she
worked was clean. ―Very few people, be they of what class they may, have any idea of the
exquisite cleanliness required in a sick room,‖ wrote Nightingale in 1859 (Dancer, 1999).
She instituted a laundry service, rigorously cleaned all medical and hospital equipment, and
―had the floors in the hospital scrubbed for the first time that anyone could remember.‖
Nightingale‘s belief in what she considered to be ―common sense‖ cleaning measures
reduced the death rate of her patients from cholera, typhus, and dysentery from 42% to a
mere 2% (Watkins, D., 1997).
U.S. Centers for Disease Control and Prevention (CDC) Sounds the Alarm
One hundred and fifty years later, despite enormous advances in understanding pathogenic
microbes and their role in hospital-borne infections, the Centers for Disease Control and
Prevention (CDC) and the U.S. news media felt the need to sound the alarm over the lack
of adherence to adequate sanitation procedures at our nation‘s hospitals (Dresher, 2002). In
this modern day and age, hospital cleaning has somehow become a neglected component of
infection control.
According to figures cited by the CDC, the estimated number of hospital-acquired
infections (HAIs) in U.S. hospitals was about 1.7 million in 2002, with 99,000 associated
deaths (Centers for Disease Control website: www.cdc.gov/ncidod/dhqp/hai.html; also:
Greider, 2007; Dresher, 2002). The statistics revealed that out of every 100 patients
admitted to hospitals, for any ailment, five to six will contract a hospital-borne infection.
Some of these patients will die from their infections.
Acknowledging that more must be done to remediate this problem, the CDC launched a
highly publicized campaign to help prevent antimicrobial resistance in healthcare settings
(CDC, 2002). Several months later, the Chicago Tribune published a three-part series of
articles that brought the entire issue of hospital-acquired infections to the forefront of the
public‘s consciousness (Chicago Tribune, 2002). The often-cited series analyzed millions
of patient records from the nation‘s 5,810 registered hospitals and from state and federal
reports. The findings were distressing:
- The Tribune's analysis, which adopted methods commonly used by epidemiologists,
found an estimated 103,000 deaths linked to hospital infections in 2000. The CDC,
which bases its numbers on extrapolations from 315 hospitals, estimated there were
90,000 that year.
12
- Three-quarters of deadly hospital infections were due to unsanitary facilities, germ-
laden instruments and unwashed hands — conditions that are all preventable with
adequate hygienic care;
- Deaths linked to hospital infections represent the fourth leading cause of mortality
among Americans — behind heart disease, cancer and strokes;
- Deaths from hospital infections kill more people each year than car accidents, fires
and drowning combined!
Despite these figures, the role of the hospital as a reservoir of infections remained a
controversial issue. Many health authorities, with the exception of those in the UK and The
Netherlands, still did not acknowledge the problem by the late 1990s (Bures et al., 2000).
Hospital-Acquired Infections Threaten Patient Safety
Since the beginning of the 21st century, evidence accumulated that hospital-acquired
infections directly threaten patient safety (Burke, 2003; Jarvis, 2004). Furthermore, it has
also been documented that patients with hospital-acquired infections have higher mortality
rates and longer hospitalizations than patients who do not develop infections (Jarvis, 1996).
The New England Journal of Medicine shed light on the dichotomy between the great
advances taking place in medical technology and the simultaneous worsening statistics
regarding hospital-acquired infections:
―Between 1975 and 1995, the number of patient days spent in the hospital
decreased by 36.5%, the average length of stay decreased by 32.9%, the number of
inpatient surgical procedures decreased by 27.3%, and the number of infections
generally decreased by 9.5%, but the incidence of hospital-acquired infections per
1,000 bed-days increased by 36.1%.‖ (New England Journal of Medicine, 2003).
This increased rate of hospital-acquired infections is taking place despite such hospital
hygiene policies as hand washing and the use of antimicrobial soaps, sanitizing gels, and
disinfectants. It is also occurring despite responsible hygienic goals stated by the Joint
Commission on Accreditation of Healthcare Organizations (JCAHO), whose accreditation
standard includes the prevention of hospital-acquired infections (Anderson et al., 2007).
JCAHO and the Institute for Healthcare Improvement are actively engaged with hospital
administrators and the general public to enhance awareness of hospital-acquired infections
(Anderson et al., 2007).
Antibiotic-resistant bacterial strains, especially MRSA, are at the heart of today‘s hospital-
acquired infection problem. Figure 4.1 depicts statistics from the CDC on the steadily
increasing percentage of S. aureus infections in hospital ICUs that are resistant to oxacillin.
The CDC, which has monitored hospital-acquired infections in its National Nosocomial
Infections Surveillance (NNIS) system since the 1970s, is concerned about the dramatic
13
increase in the hospital-acquired infections rate during the past 20 years — from 7.2 per
1,000 patient-days in 1975 to 9.8 per 1,000 patient-days in 1995 (Greider, 2007).
Figure 4.1 — This graph, presented by the Centers for Disease Control and
Prevention (CDC), is based on data provided by the National Nosocomial Infections
Surveillance System (NNIS). It demonstrates the steady increase in the percentage of
S. aureus infections in hospital ICUs that are resistant to oxacillin. Resistant strains
are now believed to be responsible for more than half of all hospital-borne infections.
Resistant strains are now believed to be responsible for more than half of all hospital-borne
infections. "The capacity of this bacterium to acquire resistance traits against antibiotics is
amazing," says Alexander Tomasz, Ph.D., head of the Laboratory of Microbiology at
Rockefeller University, New York. (Tomasz, 2001)
One possible reason for this is that the liberal use of antibiotics since 1970s has replaced
attention to rigorous hygiene (Greider, 2007). Betsy McCaughey, founder of the
Committee to Reduce Infection Deaths (RID), believes it is no coincidence that large
increases in resistant germs are marked by this period of antibiotic excess (Greider, 2007).
The Financial Burden of Hospital-acquired Infections
Notwithstanding the loss of health and life, hospital-borne infections are a huge financial
burden on the nation‘s healthcare system. The CDC estimated in early 2009 that hospital-
acquired infections cost health facilities an additional $28-45 billion per year. (Scott, 2009)
Several other studies, nationwide and in the State of Pennsylvania, have also been
14
conducted to quantify this financial burden (Anderson et al., 2007; Pennsylvania Health
Care Cost Containment Council, 2006).
Anderson et al., (2007) estimated the cost of healthcare-associated infections during 2004
in a network of 28 community hospitals in the southeastern region of the U.S. The cost of
these infections were then compared to the amount budgeted for infection control programs
at the hospitals. The researchers calculated weight-adjusted mean cost estimates per
episode of infection as follows:
- $25,072 per episode for ventilator-associated pneumonia
- $23,242 per hospital-acquired blood stream infection
- $10,443 per surgical site infection
- $758 per catheter-associated urinary tract infection
The median annual cost of hospital-acquired infections reported in the study was $594,683
per hospital. The total annual cost for the twenty-eight hospitals in the study was greater
than $26 million.
The problem is that these hospitals budgeted only a median cost of $129,000 for infection
control. Hence, the actual median annual cost of hospital-acquired infections in the study
was 4.6 times more than the amount budgeted for infection control. This led the researchers
to conclude that the economic cost of hospital-acquired infections in the study was
―enormous.‖ To combat this problem, the researchers suggested that more spending for
infection control measures is the essential missing component of successful infection
control programs.
Dancer (1999) pointed to the financial burdens facing hospitals in the UK, and their
implications in healthcare quality. He noted that resistant infections have become a serious
problem, primarily because financial constraints have reduced general cleaning in hospitals
to a ―bare minimum.‖ He cited a survey by the Infection Control Nurses Association
revealing that contractors‘ cleaning cloths and mops had routinely been left unwashed on a
daily basis, and that adequate cleaning requirements were omitted from contracts due to
cost cutting. Clearly, this is not an acceptable situation.
To bring much needed attention with the goal of effective solutions to the problem of
hospital-acquired infections, in 2005 the Pennsylvania Health Care Cost Containment
Council (www.phc4.org) made a deliberate decision to publish actual infection data in 168
general acute care hospitals in the state (Pennsylvania Health Care Cost Containment
Council, 2006). This study marked the very first time that actual infection data, rather than
guarded estimates or extrapolations, were collected directly from hospitals and made
available to the public. The study received national attention in the media. Policymakers
and healthcare executives took notice.
The results of the Council‘s study were shocking, but of no surprise to hygiene experts:
- 19,154 cases of hospital-acquired infections were reported, up significantly from
11,600 the year before (2004);
- The infection rate was 12.2 per 1,000 cases (1.22%);
15
- The mortality rate among infected patients was 12.9%, versus 2.3% for patients
without infections;
- Patients with infections averaged 20.6 days in the hospital, versus 4.5 days for those
without infections;
- The average hospital cost for patients with infections was $185,260, versus $31,389
for those without infections;
- Estimated total hospital charges for infected patients in the State of Pennsylvania
were on the order of $3.5 billion.
The study proved that hospital-acquired infections were very expensive and posed a direct
threat to patient safety and healthcare quality in the State of Pennsylvania.
In addition to bringing the problem out into the open, the study accomplished one more
very important objective: by reporting its findings, the Council established a baseline
against which future performance of individual hospital infection control and prevention
programs could be measured.
Probably because of the extent of the hospital-acquired infection problem, both in terms of
human life and costs to the State of Pennsylvania, the Governor of Pennsylvania went on
record to say he wants to revoke licenses of hospitals that don‘t comply with effective
infection measures (Sunday Patriot-News, May 5, 2007).
In response to this problem, the state‘s VA hospitals have launched leadership roles to try
to eliminate hospital pathogens (Sunday Patriot-News, May 5, 2007). The Pittsburgh VA
hospital, for example, launched a ―Getting to Zero‖ MRSA infections campaign. All other
VA hospitals in Pennsylvania launched similar programs in 2008.
The Pittsburgh VA‘s ―Getting to Zero‖ program includes such activities as testing all
patients, isolating infected patients, disposing gloves and gowns in infection rooms, and
employing disinfection procedures frequently. The measures are working: the incidence of
MRSA has been reduced from 60 cases to 17 cases within a specific time frame since the
program was adopted. Infection rates at the hospital‘s surgical unit have been reduced by
78%, a very significant measure of progress (New York Times, July 27, 2007). The success
of these simple measures, as well as successes from aggressive campaigns in the
Netherlands and in Finland, has fueled a national debate on whether hospitals were
previously doing enough to combat dangerous pathogens.
The Pennsylvania hospital infection disclosure program has caught the attention of other
states. By the end of 2007, 19 states required hospitals to publish their infection statistics.
In September 2007, the New York City Health and Hospitals Corporation, the nation‘s
largest public health system which treats 1.3 million patients each year, began releasing
infection data to the public on its website, www.nyc.gov/hhc, from its 11 hospitals (New
York Times, September 7, 2007). This measure was seen as a very bold step because it
enabled advocacy groups, as well as patients, to scrutinize hospital hygiene conditions.
16
New Jersey and Illinois are expected to require hospitals to screen intensive care patients
for MRSA in the very near future (New York Times, July 27, 2007). And in New York, the
state‘s Health Department announced it will be issuing hospital ‗report cards‘ in 2009.
Needless to say, public reporting of infection statistics has paved the way for a change in
thinking and the beginning of new and, hopefully, innovative processes to reduce hospital-
acquired infections. Open discussions among patients, policymakers, purchasers, and
medical professionals are being facilitated across the country — challenging a once
powerful myth that hospital-acquired infections are inevitable.
Medicare Is Changing How Hospitals Will Do Business
No matter what good intentions hospital administrators had and/or communicated to
patients and stakeholders to combat hospital infections, antibacterial initiatives have been
generally unsuccessful, until recently. A case can be made that not enough effort was put
forth to reduce hospital-acquired infections because there were no economic incentives to
do so. A case could also be made that there were financial disincentives to control hospital
infections, as long as insurance companies, including Medicare, were footing the bill.
Dr. Richard P. Shannon of the Allegheny General Hospital in Pittsburgh questioned
whether hospitals don‘t mind treating infections ―because they get paid for it.‖ (New York
Times, July 27, 2007).
Statistics from The Pennsylvania Health Care Cost Containment Council‘s 2006 report
shed some light on Dr. Shannon‘s allegations:
- The average charges for cases with hospital-acquired infections were $185,000,
versus $31,389 for cases without infections.
- The average insurance payments for cases with hospital-acquired infections were
$53,915, versus only $8,311 for cases without hospital-acquired infections.
This scenario is changing.
In August 2007, Medicare announced that, starting in October 2008, the Agency would no
longer pay the costs of treating certain hospital-acquired infections. Furthermore, hospitals
have been forbidden to pass the additional costs of hospital-acquired infections to their
patients.
This federal administrative ruling clearly demonstrates the government‘s position that
Medicare is not responsible for ―preventable‖ errors, injuries and infections at hospitals
(New York Times, August 19, 2007).
Medicare estimates that this ruling will save the Agency $20 million each year. But, more
importantly, the U.S. government believes that the financial disincentive of its ruling will
force hospitals to find better ways to improve patient care.
17
Since Medicare pays approximately 40% of nation‘s annual hospital bill, the agency‘s
actions will have an enormous impact on the financial well-being of the hospital industry
(NPR, August 28, 2007). That is, of course, unless the industry can get its infection rate
down to zero — goals that the State of Pennsylvania hopes to achieve.
The big question is whether private insurers will consider making similar changes in their
coverage of ―preventable‖ hospital-acquired infections. Should insurers follow Medicare‘s
suit, the added pressure on hospitals to reduce their infection rates will become enormous.
Clearly, the time is right for hospitals to consider and adopt effective antimicrobial
measures, both conventional and innovative, to get hospital-acquired infection rates down
to zero.
In subsequent chapters, a case will be made that the high antimicrobial efficacies of copper
touch surfaces, in conjunction with other measures, could be an important tool to help
hospitals ―get to zero.‖
Chapter Summary
In this chapter, the following points have been demonstrated:
- Hospital-acquired infections have increased dramatically during the past 20 years
due to the lack of sanitary conditions, germ-laden instruments, unwashed hands,
and the emergence of resistant bacteria.
- Hospital-acquired infections directly threaten patient safety. 94,360 cases of
invasive MRSA occurred in the United States in 2005. Approximately 20% of those
infected, or 18,650 patients, died from their infections.
- More people die from ―preventable‖ MRSA infections each year than from
HIV/AIDS, Parkinson‘s disease, emphysema or homicides.
- Hospital-acquired infections are a huge financial burden on the nation‘s healthcare
system; additional health facility costs are estimated to be between $28 billion and
$45 billion per year.
- Long-term care facilities, such as nursing homes, chronic disease hospitals,
rehabilitation centers, foster and group homes, and mental institutions, as well as
ambulatory care facilities and dental offices, are also common breeding grounds for
dangerous and resistant pathogens.
- MRSA, a resistant strain of bacteria formerly restricted to hospital and long-term
care environments, now accounts for 52% of all S. aureus hospital-acquired
infections;
18
- Hand washing is necessary but insufficient to control MRSA in health-related
facilities.
- Pressures from recently-released public hospital infection data and financial
pressures from Medicare‘s decision to not pay for preventable hospital-acquired
infections beginning in October 2008 has prompted hospital administrators to seek
cost-effective measures to reduce the incidence of these infections. These recent
events are paving the way for the implementation of innovative antimicrobial
measures, including the use of antimicrobial copper alloys as touch surfaces in
healthcare facilities as a supplement to, but not a substitute for, existing cleaning
and sanitization procedures.
19
V
Toxic Microbes of Concern to the Healthcare Industry
This chapter summarizes the prevalence, characteristics, and toxicities of specific microbial
pathogens that are of most concern to the healthcare industry. The following organisms will
be discussed at various lengths:
- Bacteria:
o Methicillin-resistant Staphylococcus aureus (MRSA)
o Vancomycin-resistant Enterococcus (VRE)
o E. coli O157:H7
o Clostridium difficile
o Acinetobacter sp.
o Klebsiella sp.
o Escherichia sp.
o Serratia sp.
o Pseudomonas sp.
o Enterobacter sp.
- Viruses:
o Influenza
o Parainfluenza
o Enteric viruses
o Hepatitis B virus
o Severe acute respiratory syndrome (SARS)–associated coronavirus
o Norwalk virus
- Fungi:
o Aspergillus sp.
o Candida albicans
o Candida glabrata
o Candida parapsilosis
o Zygomycetes sp.
Bacteria of Concern to the Healthcare Industry
The most common pathogens responsible for hospital-acquired infections are Gram-
negative rods, including E. coli, Pseudomonas sp., Enterobacter sp., and Gram-positive
cocci such as Enterococcus sp. and S. aureus (Bures et al., 2000). These and other common
bacterial pathogens were described by Dancer (1999) and are summarized in this chapter.
The pathogen that has been of greatest concern to hospitals in recent years is called
Methicillin-resistant Staphylococcus aureus (MRSA). Due to its resistance to antibiotic
20
drugs and its prevalence in healthcare environments, it is worthwhile to discuss this
microbe, and the challenges of controlling it, in more detail.
MRSA: A Dangerous Threat Becomes Prevalent in Hospitals Today
It has been some 60 years since penicillin, the first antibiotic miracle drug, was used to
treat a wide variety of bacterial infections. But this drug and its stronger successors have
been challenged in recent years as a result of their inappropriate use and overuse, thereby
enabling the evolution of resistant strains of bacteria.
A strain of Staphylococcus aureus bacteria discovered in the 1960s, called Methicillin-
resistant Staphylococcus aureus (MRSA), has defied nearly all antibiotics (Stewart and
Holt, 1962).
MRSA infections cause a broad range of symptoms, depending on the part of the body that
is infected (e.g., skin, wounds from surgery, burns, catheter sites, eyes, blood, etc.). Often,
MRSA colonizes human skin, leading to localized superficial abscesses.
Endemic today in many hospitals, MRSA has become one of the leading causes of hospital-
acquired pneumonia and surgical site infections. It is also the second leading cause of blood
stream infections (Boyce et al., 1994). Serious bone and skin infections are common
symptoms of the infection.
Sometimes, MRSA carriers do not have symptoms at all. Some people can carry MRSA for
months, even after their infections have been treated. In other patients, the infection can
become deadly within days.
Hospital-acquired MRSA Infections Have Increased Dramatically
MRSA infections in hospitals have increased relentlessly (by over 40%) from 1994 to 1999
(source: Johns Hopkins Infectious Disease website, see Reference Section). MRSA now
accounts for 52% of all S. aureus hospital-acquired infections (National Nosocomial
Infections Surveillance System Report, 2000). A CDC report updates that to 63% of the
total number of staph infections in 2004 (CDC DHQP, October 2007).
The first thorough study to quantify the disease‘s prevalence in the USA, conducted by the
CDC, was published in the Journal of the American Medical Association (Kleve‘s et al.,
2007) and presents the most current statistics available as of this writing. The research team
estimated the rate of invasive MRSA in 2005 to be 31.8 per 100,000 persons.
Based on the data, it was estimated that 94,360 cases of invasive MRSA occurred in the
United States in 2005. This rate of infection was perhaps twice as high as what experts had
expected. The study concludes that MRSA is a major public health problem primarily
related to healthcare but no longer confined to intensive care units, acute care hospitals, or
healthcare institutions. However, the study says about 85% of all invasive MRSA
infections were associated with healthcare.
21
Approximately 20% of those infected, or 18,650 hospitalized patients, died from the
MRSA infection. If this mortality rate is accurate, then, according to the New York Times,
more people died in 2005 from MRSA infections than from HIV/AIDS, Parkinson‘s
disease, emphysema, or homicides (Sac, New York Times, October 17, 2007).
Once inside a hospital environment, MRSA is extremely difficult to eradicate (Nettleman et
al., 1991). MRSA creates chronic endemics in hospitals, punctuated by episodes of cross-
infection and outbreaks. Only 15% of reported outbreaks have been completely eliminated
(BioHealth Partnership, 2007).
Common factors associated with acquiring hospital-borne MRSA include prolonged
hospital stays, the use of broad spectrum antibiotics, duration of antibiotic usage, residence
in intensive care or burn units, the presence of surgical wound sites, and proximity to other
patients who are infected by the organism (Boyce et al., 1994).
Hand Washing, Necessary But Insufficient to Control MRSA in Neonatal Intensive
Care Units
MRSA is generally spread through direct contact via the hands of healthcare workers
(Boyce, 1992; Hota, 2004). The bacteria are also associated with hospital dust, bedding,
curtains, mops, gowns, gloves, and nurses‘ uniforms. In addition to hands, the bacteria have
been isolated from TV knobs, cushions, computer keyboards, writing pens, stethoscopes,
and ventilation grilles (Kumari et al., 1998; Ndawula, 1991; Oie and Kamiya, 1996).
Hand washing reduces the spread of hospital-acquired infections from Gram-negative
bacteria (GNB), such as coagulase-negative staphylococci (CNS) and Staphylococcus
aureus. However, Klingenberg et al., (2001) found that hospital staff directly involved in
patient care exhibit more antibiotic-resistant organisms than staff who are not directly
involved with patient care. In two New York City neonatal intensive care units (NICUs),
Aiello et al., (2003) found that the hands of nurses harbored significantly more S.
epidermidis strains resistant to amoxicillin/clavulanate, cefazolin, clindamycin,
erythromycin, and oxacillin, as well as more S. warneri strains resistant to
amoxicillin/clavulanate, cefazolin, clindamycin, and oxacillin. These findings suggest that
hand washing alone is unsuccessful in deterring resistant strains and underscores the
importance of improving infection control practices.
MRSA Viable for Months on Many Touch Surfaces
Both MRSA and Methicillin-susceptible Staphylococcus aureus have been found to be
viable for as long as nine weeks, despite drying. The pathogen has been found to survive on
plastic laminate surfaces for up to 2 days under experimental conditions (Beard-Pegler et
al., 1988; Duckworth and Jordens, 1990).
MRSA was also found to survive for nearly 6 months (175 days) under desiccating
conditions (Wagenvoort and Penders, 1997). An outbreak in the U.K. was prolonged
because ward cleaning did not include washing curtains around patient beds (Dancer, 1999,
unpublished observations).
22
Probable Reservoirs for MRSA Infection
In an intensive care unit with patients who tested positive for MRSA, the colonization rate
of MRSA, Enterobacter sp., and Enterococcus sp. on computer keyboards and faucet
handles was found to be greater than on other well-studied surfaces (Bures et al., 2000).
Computer keyboards were uniformly contaminated throughout the intensive care unit,
regardless of proximity to the infected patients. Faucet handles had cross-infection rates
statistically similar to those for keyboards. Since contamination rates on keyboards and
faucet handles were found to approach and often exceed levels for direct patient contact
surfaces identified in previous studies, Bures et al., (2000) concluded that both of these
items are likely ―reservoirs of hospital-acquired pathogens and vectors for cross-
transmission.‖ The investigators recommended that institutional hygiene policies be revised
to include installation of plastic keyboard covers with daily cleaning procedures,
replacement of all faucet handles with noncontact-controlled sinks, and hand washing
requirements after contact with patients in the ICU. Replacement of faucets by those made
from antimicrobial materials or coating keyboards with antimicrobial formulations was not
considered.
Other common touch surfaces in hospital environments are probable sources of infection.
Examples of common surfaces in hospitals include instrument handles, equipment carts,
intravenous poles, push plates, grab bars, panic bars, trays, pans, bedrails, walkers,
handrails and stair rails. This hypothesis is being confirmed by current research (See
Chapter XVII).
Precautionary Measures Needed to Control MRSA in Long-term Care Facilities Long-term care facilities (nursing homes, chronic disease hospitals, rehabilitation centers,
foster and group homes, mental institutions) are common breeding grounds for various
pathogens, including MRSA. The incidence of illness among the nation‘s 1.5 million
nursing home residents has increased in recent years. Smith and Rusnak (1997) report that
the risk for infection among residents is similar to that of patients in acute care hospitals. In
fact, almost as many hospital-acquired infections occur annually in America‘s long-term
care facilities as in our hospitals. Furthermore, resistant strains tend to persist and become
endemic in long-term care facilities (Strausbaugh et al., 1996). For these reasons, beginning
in the 1980s, federal and state regulations mandated the implementation of infection control
programs in long-term care units. Sometimes, these programs are established to meet
hospital standards.
According to Smith and Rusnak (1997), long-term care facilities should consider
precautionary measures, such as surveillance, isolation, outbreak control, resident care and
employee health evaluations, as are now being conducted in some hospitals (Chapter IV).
The authors did not recommend antimicrobial surfaces as a measure to combat infection
from cross-contamination.
23
Community-acquired MRSA on the Rise
Recently, MRSA has taken a new turn by spreading outside of health-related facilities.
Community-acquired outbreaks have been reported among prison inmates, contact athletes,
military recruits, children in daycare centers, and crewmembers of a naval ship. This
indicates that the epidemiology of MRSA is changing.
Salmenlinna et al., (2002) report that of 526 MRSA-positive persons who had been
hospitalized in Finland between 1997–1999, 21% had what is now being referred to as
―community-acquired‖ MRSA. Sinderman et al., (2004) report a 2002 outbreak of 235
community-acquired MRSA infections among military recruits in the southeastern U.S.
The researchers concluded that the unique close environment of recruits might have
contributed to the spread of the disease. In 2003, the CDC reported that athletes in contact
sports where equipment is shared and where there is potential for skin abrasions and trauma
are at risk for acquiring MRSA (CDC MMWR Weekly, 2003).
Treating MRSA Is Difficult
MRSA cannot be treated effectively with common antibiotics, such as Methicillin,
nafcillin, cephalosporin or penicillin. Therefore, medical practitioners must resort to
unusual, expensive and potentially dangerous pharmaceutical cocktails in their attempt to
cure patients.
Vancomycin, one of the most potent antibiotics available and a drug of last resort that is
restricted for hospital use, can often successfully treat MRSA. But, as the use of
vancomycin has skyrocketed, all five major strains of MRSA have either shown signs of
resistance or have developed an actual resistance to vancomycin, according to scientists at
the University of Bath, University of Bristol and Southmead Hospital in the UK (Howe et
al., May 2004).
Health authorities have been alarmed about three cases of vancomycin-resistant
Staphylococcus aureus that have been confirmed in the USA as of June 2004 (BBC News,
June 18, 2004). Should this strain have the opportunity to spread, a serious medical crisis
would surely develop. ―If we lose vancomycin completely as a treatment, we could see a
doubling in deaths over the next five years,‖ Dr. Mark Enright of the University of Bath
told the BBC.
New Antibiotics Are Not Being Developed to Combat MRSA
The time was when R&D efforts successfully provided new drugs in time to treat bacteria
that became resistant to existing antibiotics. Recently, however, the pharmaceutical
industry has not been motivated to develop a pipeline of stronger antibiotics to meet the
threat from Methicillin- and vancomycin-resistant strains of bacteria. According to a report
on the CBS-TV news show, 60 Minutes, of the 400 new pharmaceutical agents that were
licensed to the FDA in 2002, none were genuinely ―new‖ types of antibiotics (CBS News,
May 2, 2004). This is because antibiotics are prescribed for only a maximum of 10 days to
two weeks and are, therefore, not as profitable as medications used daily for chronic
conditions, such as heart disease, high blood pressure, or high cholesterol. The Infectious
Diseases Society of America noted, ―a potential crisis is looming due to the marked
decrease in industry R&D, government inaction, and increasing prevalence of resistant
24
bacteria‖ (www/idsociety.org). Since it takes nearly 15 years and $800 million to $1.7
billion to research and test any new drug for FDA approval, the medical community is not
equipped to protect patients from these new bacterial threats.
Infectious disease experts believe we are running out of time. ―With increasing vancomycin
resistance, we are going to see a significant increase in mortality,‖ said Dr. Enright. ―The
problem is much more serious than was previously thought.‖ (BBC News, June 18, 2004).
For further information about MRSA and a list of recent publications dealing with
worldwide MRSA infection in intensive care units, teaching hospitals, surgical wards,
neonatal units, dermatology wards, children‘s hospitals, outpatient facilities and long-term
care facilities around the world, go to the Infection Control and Hospital Epidemiology
website at: www.ichejournal.com/srchResults.asp.
Vancomycin-resistant Enterococcus (VRE)
Although not especially virulent, enterococci have become the second most common
nosocomial pathogen and are the third leading cause of nosocomial bloodstream infections.
Enterococci are intrinsically resistant to many common antibiotics. Residing in the
gastrointestinal tract of infected patients, VRE persists for a long period of time when
colonized in the body. This strain is more resistant to disinfectants and antibiotics than
Staphylococcus sp. and survives for a longer period than Staphylococcus sp. in hospital
environments (Gray, 1992).
E. coli O157:H7
This toxic strain of bacteria is most often associated with the consumption of contaminated
beef or unpasteurized milk, and more recently, with contaminated spinach, which in a 2006
outbreak, infected 187 people and resulted in three deaths (FDA, October 2, 2006). But the
virulent microbe can also be transmitted via person-to-person contact or by contact with
contaminated surfaces. In healthcare facilities where patient immunity is often
compromised, E. coli O157:H7 infections can cause very severe symptoms, including
diarrhea, abdominal pain, vomiting, and death. It is important to note that E. coli is able to
proliferate in hospitals because of its resistance to multiple antibiotics. Conditions that
predispose patients to hospital-acquired E. coli infections are often invasive devices such as
catheters and respirators. Nursing home patients infected with E. coli prior to hospital
admission are at a higher risk of developing multiple-antibiotic-resistant E. coli infections
(University of Georgia website:
http://www.arches.uga.edu/~anita30/Escherichia%20coli.html).
Clostridium difficile
This anaerobic Gram-positive bacterial rod, which is found in diarrhea, contains spores that
can survive for months. This is why common sources of hospital-acquired C. difficile
include bedclothes, commodes, and floors under beds, bedpans, blood pressure cuffs, walls,
washbasins, and furniture (Samore et al., 1996; Kim et al., 1981; Fekety et al., 1981). The
organism has been found in low numbers on shoes and on stethoscopes (Fekety et al.,
1981). Hospital floors have remained contaminated with C. difficile for up to 5 months
(Kim et al., 1981).
25
Spores of C. difficile are durable and are resistant to usual cleaning methods (Hota, 2004)
and infection control measures (e.g., vigorous cleaning, antibiotics) can be ineffective after
an outbreak. Contamination of the inanimate environment by C. difficile has been reported
to occur in areas in close proximity to infected or colonized patients. Contamination rates
have been as high as 58% (Hota, 2004).
The findings of a study of endemic C. difficile (Samore et al., 1996) revealed a correlation
between the degree of colonization of healthcare workers‘ hands and environmental
contamination with C. difficile. The data suggest that environmental surfaces serve as a
reservoir that permits the cross-colonization of patients after they have had contact with a
healthcare worker and that, in environments in which C. difficile is endemic, specific
isolates likely predominate (Samore, et al., 1996; Fawley and Wilcox, 2001).
Teare et al., (1998) cite a difficult-to-remove cage surrounding radiators in a hospital that
contained thick dust and dry fecal material infected by C. difficile. An outbreak at this
hospital began when the radiators were turned on and pathogens were released. Thermal
convection may have played a part in disseminating spores around the hospital and
infecting susceptible patients. The frequency of bacterial dispersion combined with the
long-term life of the spores explained the difficulty in eliminating the bacteria once it
became established in the hospital environment. Safar et al., (1998) describe a seven-year
study in an American hospital demonstrating that a sustained decrease in C. difficile was
observed when cleaning was included as part of an aggressive infection-control program.
Acinetobacter sp.
Acinetobacter sp. can survive for long periods of time on dry surfaces and dust particles.
One species, Acinetobacter radioresistens, is reported to have a phenomenal ability to
survive on dry surfaces — live bacteria were discovered on glass cover slips after 157 days
(Jawad et al., 1998). Acinetobacter baumannii are strongly associated with environmental
contamination (Hota, 2004). Spread of Acinetobacter baumannii via droplets has been
suggested from air sampling with culture plates (Simor et al., 2002).
Acinetobacter baumannii isolates have been marked by increased resistance to antibiotics
and have been the cause of recalcitrant hospital-acquired outbreaks (Hota, 2004). The
organism has been isolated throughout the inanimate environment — on the beds of
colonized patients and on nearby surfaces (e.g., on mattresses and bedside equipment), in
hospital rooms (e.g., on floors, sinks, countertops and door handles), and in room
humidifiers (Simor et al., 2002; Das et al., 2002).
Klebsiella sp. and Escherichia sp.
Klebsiella sp. and Escherichia sp. pathogens are often found in mops and buckets in
hospital environments. These bacteria survive for long periods of time on surfaces (Forder,
1973).
26
Serratia sp.
This bacterium was found on shaving brushes in an intensive care unit (Whitby et. al.,
1972).
Pseudomonas sp.
This bacterium frequents sinks, basins and respiratory equipment (Levin et al., 1984).
Enterobacter sp.
This bacterium was identified on parenteral feeds (Casewell et al., 1981).
Viruses of Concern to the Healthcare Industry
Environmental cleaning is an integral part of infection-control strategies for influenza,
parainfluenza, enteric viruses, hepatitis B virus, and severe acute respiratory syndrome
(SARS)–associated coronavirus. The following summary and references are largely
excerpted from Dr. Bala Hota‘s paper on contamination, disinfection, and cross-
colonization of pathogens in the hospital environment (Hota, 2004).
Influenza
The influenza virus, which is spread through respiratory droplets and possibly through
airborne droplet nuclei, can contaminate the environment. It persists after drying and
becomes re-aerosolized from floor sweeping. The influenza virus can survive for 24–48
hours on nonporous surfaces. Viable viruses can be spread on the skin, suggesting that
environmental contamination can lead to cross-infection of patients via the hands of
healthcare workers (Bridges et al., 2003). Parainfluenza virus is resistant to drying and can
survive for 10 hours on nonporous surfaces and for 16 hours on clothing (Brady et al.,
1990).
Rotavirus and Norovirus
Human enteric viruses can cause institutional outbreaks (Rogers et al., 2000; Green et al.,
1998; Centers for Disease Control and Prevention, 2002). Rotavirus, which contaminates
and survives on surfaces, is a well-known cause of outbreaks in daycare centers and
healthcare settings (Rogers et al., 2000). Norovirus has caused outbreaks on cruise ships, in
hospitals, and in hotels (Cheesebrough et al., 2000; Marks et al., 2000; Green et al., 1998;
Centers for Disease Control and Prevention, 2002).
Hepatitis B
Individuals without immunity to hepatitis B virus (HBV) should be considered to be at risk
for infection from contaminated environmental sources.
SARS-Associated Coronavirus
SARS-associated coronavirus is believed to be spread mainly via respiratory droplets,
although fecal-oral transmission and transmission via surface contamination may also
occur. The virus has been found to survive for 24–72 hours on plastered walls, plastic
27
laminate surfaces (e.g., Formica), and plastic surfaces and is viable in excreted feces and
urine for at least 1–2 days at room temperature (World Health Organization website, 2004).
Norwalk Virus
The Norwalk virus is a potent pathogen that causes gastroenteritis (vomiting). The virus
can precipitate an epidemic that can close entire hospital wards. Symptoms from the
Norwalk virus generally affect older patients and are revealed 48 hours after exposure. The
virus disperses via vomit droplets and can easily reside on toilets, floors, curtains and
carpets.
Fungi of Concern to the Healthcare Industry
Candida sp.
Molecular typing studies of yeast from patients, from the hands of healthcare workers and
from the environment suggest that fomites may play a role in the spread of Candida
albicans, Candida glabrata, and Candida parapsilosis. The following summary, with
references, was excerpted from Hota (2004).
Experimental inoculation of C. albicans and C. parapsilosis on dry surfaces shows that
these fungi can survive for 3 days and 14 days, respectively (Traore et al., 2002). This
could indicate that surfaces can potentially be contaminated with these pathogens.
An epidemic spread of Candida infection has been documented in which environmental
sources (e.g., a blood pressure transducer or irrigating solution) were suspected (Vazquez et
al., 1998; Vazquez et al., 1993).
Evidence of an environmental reservoir of endemic C. albicans and C. glabrata has been
suggested through the use of molecular typing of Candida isolates recovered from the
environment and from patients who underwent bone marrow transplantation (Vazquez et
al., 1998). The strain types of Candida isolates acquired by patients were identical to those
found on the hospital surfaces of rooms where the patients were housed, prior to patient
acquisition of infection.
Aspergillus sp. and Zygomycetes sp.
Aspergillus and Zygomycetes species cause hospital-acquired skin infections from
contaminated fomites. Infections have been associated with the use of arm boards or
bandages by patients who have intravascular catheters, as well as with elasticized surgical
bandages, hospital construction activity, and postoperative wounds (Fridkin and Jarvis,
1996).
28
Chapter Summary
In this chapter, the following points have been demonstrated:
- Hospital-acquired infections have increased dramatically during the past 20 years
due to the lack of sanitary conditions, germ-laden instruments and unwashed hands,
all of which contribute to the emergence of resistant bacteria.
- Hospital-acquired infections directly threaten patient safety.
- 94,360 cases of invasive MRSA were estimated to have occurred in the United
States in 2005. Approximately 20% of those infected, or 18,650 patients, died from
their infections.
- More people die from ―preventable‖ MRSA infections than from HIV/AIDS,
Parkinson‘s disease, emphysema, or homicides.
- Long-term care facilities, such as nursing homes, chronic disease hospitals,
rehabilitation centers, foster and group homes and mental institutions are also
common breeding grounds for dangerous and resistant pathogens.
- MRSA, a resistant strain of bacteria formerly restricted to hospital and long-term
care environments, now accounts for 63% of all S. aureus hospital-acquired
infections.
- Hand washing is necessary but insufficient to control MRSA in health-related
facilities.
- New antibiotics are not being developed to combat MRSA and other resistant
strains of bacteria, largely due to economic reasons pertaining to the pharmaceutical
industry.
- Touch surfaces in hospitals, such as faucet handles, computer keyboards, instrument
handles, equipment carts, intravenous poles, push plates, grab bars, panic bars,
trays, pans, bedrails, walkers, handrails and stair rails, are reservoirs for hospital-
acquired infection.
29
VI
The Case for Using Copper Touch Surfaces to Kill
Disease-causing Bacteria in Healthcare Facilities
The following key points about copper‘s antimicrobial properties were established in
previous chapters:
- Copper and copper compounds are antimicrobial agents that kill and inhibit the
growth of algae, molds, bacteria, viruses and fungi.
- Copper and its compounds are used as fungicides and bactericides in a wide range
of industrial and consumer applications, including agricultural sprays, marine
paints, oral hygiene products, medicines and other disinfectant products.
- Copper and copper alloy surfaces are biocidal agents that effectively kill 99.9% of
bacteria* within two hours, when cleaned regularly.
The following key points have also been established about hospital-acquired infections:
- There is a lack of consistent adherence to adequate sanitation procedures at our
nation‘s hospitals and long-term care facilities.
- The rate of hospital-acquired infections has actually increased in the past 20 years.
- Hospital-acquired infections threaten patient safety.
- Hospital-acquired infections affect approximately 2 million Americans every year
and result in some 99,000 deaths annually — more than car accidents, fires and
drowning combined.
- MRSA is a significant resistant bacteria strain that thrives in health-related facilities
in the U.S. and abroad.
- MRSA now accounts for 63% of all S. aureus hospital-acquired infections.
- 94,360 cases of MRSA were estimated to have occurred in the USA in 2005.
Twenty percent of infected patients died from the infections.
- Health authorities are alarmed about recent cases of Vancomycin-resistant
Staphylococcus aureus that have been confirmed recently.
- New classes of antibiotics may not be available to the market for many years.
- Resistant infections cost the healthcare industry up to an additional $28–45 billion
per year in treatment.
- Hospitals have begun to publish infection statistics for the benefit of the public.
- Medicare stopped paying for many hospital-acquired infections in October 2008,
and insurance companies are deciding whether to follow suit. These developments
will place extraordinary pressures on hospitals to reduce patient infection rates.
30
Objectives of This Chapter
In this section, it will be demonstrated that:
- Frequently touched surfaces and medical equipment can become contaminated with
hospital-acquired pathogens.
- Microbes are infectious at very low doses and can survive for hours to weeks on
nonporous surfaces.
- Kuhn‘s 1983 study reveals that copper alloys inhibit the growth of pathogenic
bacteria that thrive on frequently touched surfaces in healthcare environments.
- Since 1999, an extensive amount of research on the antimicrobial efficacy of copper
alloys as frequently touched surfaces has taken place. The results, presented in this
paper, have been extremely positive for copper.
- Antimicrobial efficacy studies on touch surfaces indicate that copper alloys can kill
99.9% of dangerous hospital-acquired microbes within two hours when cleaned
regularly.
- 99.9% of E. coli O157:H7 can be completely killed within two hours by copper (see
Chapter VII for a more detailed summary of recent research).
- The number of viable MRSA colony forming units, a very problematic cause of
hospital infections, can be reduced 99.9% by copper alloy surfaces within two hours
when cleaned regularly (see Chapter VIII for a more detailed summary of recent
research).
As always, it‘s important to remember that within the U.S., promotional materials
developed to support the sale of antimicrobial copper touch surface products can only claim
antimicrobial efficacy against E. coli O157:H7, Methicillin-resistant Staphylococcus
aureus, Pseudomonas aeruginosa, Enterobacter aerogenes, and Staphylococcus aureus, as
per the EPA registration. Claims that organisms are killed within any time frame less than
two hours have not been approved by the EPA.
Hospital Surfaces and Hospital-acquired Infections
It has been proven that touch surfaces in hospitals can become contaminated with toxic
microorganisms (Hota, 2004). There is compelling evidence that Clostridium difficile,
vancomycin-resistant enterococci, and Methicillin-resistant Staphylococcus aureus are
toxic pathogens on hospital surface materials. Also, there is evidence for probable survival
of norovirus, influenza virus, severe acute respiratory syndrome-associated coronavirus,
and Candida species on surfaces. A summary table (Table 6.1) of eleven hospital-acquired
pathogens that have been found on surfaces, along with their survival times and
recommendations for decontamination, are reproduced from Hota (2004).
31
Pathogen Types of environmental contamination
Length of survival of organism
Evidence of transmissiona
Recom-mended isolation precautions[2]
Recommendations for decontamination
Influenza virus Aerosolization after sweeping[3]; survival on fomites
24–48 hours on nonporous surfaces[3]
Fomites to hands of HCWb[3]
Droplet Standard EPA-approved disinfectant or detergent-disinfectant[4]
Parainfluenza virus
Survival on clothing and nonporous surfaces
10 hours on nonporous surfaces; 6 hours on clothing[5]
Not proven Contactc Standard EPA-approved disinfectant or detergent-disinfectant[4]
Noroviruses Persistent outbreaks on ships[6]; extensive environmental contamination[7];
possible aerosolization[8]
14 days in stool samples[6]; 12 days on carpets[7]
Not proven Standard 10% Sodium hypochlorite solution or other germicide[6]
Hepatitis B virus
Environmental contamination with blood
7 days[9] Lancets, EEG electrodes in outbreaks[10,11]; nosocomial transmission to HCW
Standard Standard EPA-approved disinfectant or detergent-disinfectant[4]
SARS-associated coronavirus
Positive results of cultures of samples from an ED environment; high secondary attack rate events (i.e., super spreading events)d[15]
24–72 hours on fomites and in stool samples[13]
No proven but suspected; clothing not clearly affected
Airborne, contact, and personal protective equipment
Standard EPA-approved disinfectant or detergent-disinfectant[14]
Candida sp. Contamination of fomites[16]
3 days for Candida albicans[17] and 14 days for Candida parapsilosis[17]
Suggested by molecular epidemiologic findings[16]
Standard Standard EPA-approved disinfectant or detergent-disinfectant[4]
Clostridium difficile
Extensive environmental contamination[18-20]
5 months on hospital floors[19]
Correlation between degree of environmental contamination and HCW hand contamination[18]
Contact Hypochlorite-based (sporicidal) products
Pseudomonas aeruginosa
Contamination of sink drains[21]
7 hours on glass slide[22]
Multiple types in environment that do not correlate with acquisition[23]; most acquisition is endogenous[21]
Contacte Standard EPA-approved disinfectant or detergent-disinfectant
Acinetobacter baumannii
Extensive environmental contamination[24,25]
33 days on plastic laminate surfaces[26]
Multiple types in environment that do not correlate with acquisition[27]
Contacte Standard EPA-approved disinfectant or detergent-disinfectant[4]
MRSA Burn units extensively contaminated[28]
≤9 weeks after drying[29]; 2 days on plastic laminate surfaces[30]
Evidence of environment-to-HCW spread[28]; phage types in environment discordant with patient phage types[31]
Contact Standard EPA-approved disinfectant or detergent-disinfectant[4]
VRE Extensive environmental contamination[32-34]
≤58 days on countertops[36]
Environment-to-HCW spread; high risk of acquisition by patients in contaminate rooms[37]
Contact Standard EPA-approved disinfectant or detergent-disinfectant[4]
NOTE: ED, emergency department; EEG, electroencephalographic; EPA, environmental Protection Agency, HCW, healthcare worker; MRSA, Methicillin-resistant Staphylococcus aureus; SARS, severe acute respiratory syndrome, VRE, vancomycin-resistant enterococci.
a From environment to HCW or to patient. b Role is minor. c In cases of respiratory infections in children. d Defined as possible fecal-oral transmission, with contamination of environment. e Highly resistant organisms only.
Table 6.1 — Summary of hospital-acquired pathogens and environmental
contamination. See Hota (2004) for the many references cited in this table.
32
To get a better sense of the extent of contamination on public surfaces and to establish
baseline information regarding areas of greatest potential exposure and public health risk,
Kelley et al. (2005) conducted the first study to quantify pathogens on public surfaces with
hygienic markers. The researchers noted that some microbes are infectious at very low
doses and can survive for hours to weeks on nonporous surfaces, such as countertops and
telephone handsets (Mahl & Sadler 1975; Bean et al. 1982; Noskin et al. 1995; Sattar &
Springthorpe 1999; Bures et al. 2000; Barker et al. 2001; Abad et al. 2001). A number of
viruses, including influenza A virus, hepatitis A virus, and herpes simplex virus, can
survive for 2–24 hours on hard surfaces (Beumer et al. 2002).
While Kelley et al. (2005) covered many different public places and their study was not
specific to hospitals, the work nevertheless produced several important observations and
conclusions regarding pathogens on public surfaces:
- 93% of samples were positive for HPC bacteria;
- 25% of samples were positive for protein (≥200 g/10 cm2);
- 20% of samples were positive for biochemical markers;
- 7% of samples were positive for coliforms; and
- 1.5% of samples were positive for fecal coliforms.
Common routes of pathogen exposure from environmental surfaces mentioned in the
Kelley et al. (2005) study included surface-to-mouth, finger contamination by hand-to-
mouth contact, and exposure to eyes, nose, cuts, and abraded skin.
A table summarizing the most contaminated surfaces in the study, according to percentages
of positive tests for protein and biochemical markers, is provided (Table 6.2). Several of
the items, such as bus rails, chairs, vending machine buttons, public bathroom surfaces,
pens, public telephones, and elevator buttons, are pertinent to hospital environments.
Surface (n) % >200g/10 cm2 Protein Test
(n)*
% Positive for Biochemical Markets (n)#
Playground equipment (42) 74 (31) 36 (15)
Bus rails/armrests (31) 61 (19) 35 (11)
Shopping cart handles (24) 54 (13) 21 (11)
Chair/seat armrests (68) 51 (35) 21 (14)
Vending machine buttons (43) 47 (20) 14 (6)
Escalator handrails (37) 46 (17) 19 (7)
Public bathroom surfaces (165) 46 (76) 25 (41)
Customer-shared pens (19) 42 (8) 16 (3)
Public telephones (47) 34 (16) 13 (6)
Elevator buttons (21) 29 ( 6) 10 (2)
* Positive protein results reading of ≥3 (>200 g/ml) with the visual assure kit. # Positive for at least one of the following: amylase, urea or hemoglobin.
Table 6.2 — Ranking of contaminated surfaces in public spaces by percentage of
surfaces positive for protein and biochemical markers. (Source: Kelley et al., 2005).
33
Antimicrobial Efficacy Experiments on Touch Materials in Hospitals
There is clearly much concern about pathogens in hospital environments and the escalating
rates of hospital-acquired infections. Conventional wisdom calls for the cleaning of
environmental surfaces via disinfection (i.e., microbial elimination via chemical agents)
and sterilization (i.e., microbial destruction on an object with heat, pressure, or chemicals)
procedures.
However, a large body of evidence has emerged that has transformed some researchers‘
thinking to an entirely new strategy: the use of inherently antimicrobial materials. While
disinfection and sterilization procedures remain essential, the use of antimicrobial materials
has the potential to become an effective supplementary strategy due to the efficacy that has
been demonstrated in independent research.
Study Demonstrates that Routine Cleaning Is Not Enough
The Centers for Disease Control and Prevention recommends thorough and frequent
cleaning of environmental surfaces found in patient rooms such as overbed tables, IV poles,
bedrails, sinks, etc. However, these guidelines are left to the discretion of the hospital, and
there are no standards, regulations or methods currently in place to ensure that these
surfaces are being cleaned properly or regularly. As discussed, it is well-documented in the
literature that surfaces in hospital rooms can be highly contaminated with a host of disease-
causing bacteria such as VRE, MRSA and C. diff. These bacteria can easily be transferred
by touch, passing from patients to healthcare workers and vice versa.
One study by Carling et al., (2005) sought to evaluate just how well surfaces are being
cleaned in hospital rooms. The study used a nontoxic, organic tracer to simulate the
behavior of microbes on typical surfaces. The tracer is invisible to the naked eye, but
fluoresces under black light and is easily removed by standard cleaning. Roughly 1,400
objects in 157 rooms in three hospitals were sprayed with the tracer unbeknownst to the
cleaning staff. The researchers monitored the rooms and observed each object under the
black light after several patients had passed through and a terminal cleaning was
conducted. The results were shocking. Only about 45% of the objects tested were properly
cleaned. This implies that standard cleaning leaves a considerable amount of microbes
behind and is not a sufficient means to control disease-causing bacteria.
Copper and Brass Doorknobs Kill Microbes in Hospitals
To the naked eye, stainless steel (88% Fe, 12% Cr) doorknobs and push plates on hospital
doors appear to be clean. Brass (67% Cu, 33% Zn), on the other hand, may not appear quite
as clean to some because of its natural coloring. Yet, when it comes to the ability of
microbial populations to survive on brass (and other copper-base alloys), it turns out that
looks are deceiving.
34
In her research paper on bacterial growth rates on stainless steel and brass published in
Diagnostic Medicine, Kuhn (1983) observed heavy growth on stainless steel of both Gram-
positive organisms and an array of Gram-negative organisms, including Proteus sp. Only
sparse growth was observed on brass doorknobs. This led the author to conclude that ―brass
is bactericidal and stainless steel is not.‖
Bacterial broths of E. coli, Staphylococcus aureus, Streptococcus group D, and
Pseudomonas sp. were then inoculated onto stainless steel, brass, aluminum and copper to
compare antimicrobial efficacies. The results, according to Kuhn, were ―striking.‖
Aluminum and stainless steel allowed heavy growth of all microbial species within eight
days. Alarmingly, most of the microbes remained on these metals after three weeks when
the investigation was terminated. Conversely, copper and brass showed little or no
microbial growth at all. In fact, copper apparently began to kill bacteria immediately and
measurably within fifteen minutes. Freshly scoured brass killed over 99.9% of bacteria
within one hour. Non-scoured brass samples killed over 99.9% of bacteria in seven hours
or less, depending upon the size of the inoculum and the condition of the surface.
Kuhn indicated other interesting points from her research (as described later by Dresher,
2002):
1) Brushed surfaces on stainless steel provide a safe haven for microbes;
2) For surfaces that are not bacteriostatic, such as aluminum and stainless steel,
germicides must be used on a regular basis;
3) Tests from this study suggest stainless steel doorknobs and push plates would have
to be sanitized as often as every two hours to match the protection naturally
provided by bactericidal copper and brass;
4) Newly installed, brushed stainless steel doorknobs and push plates were less
hygienic than the oxidized brass fixtures that had been recently removed.
Major New Initiatives in Evaluating the Potential for Copper Alloys to Kill Microbes
in the Healthcare Environment:
Kuhn‘s 1983 study, in conjunction with earlier studies mentioned in Chapter III regarding
antimicrobial properties of copper, piqued the interest of the copper industry and prompted
it to conduct a full investigation into the antimicrobial efficacy of copper and its alloys.
Since 1999, an extensive amount of research has taken place and the results have been
extremely promising (Chapters VII, VIII, IX, X, XI, XII, XIII). This has prompted the
copper industry to conduct more comprehensive studies with the EPA in order to achieve
an official antimicrobial registration for copper and copper alloy touch surfaces as a public
health product (Chapter XV). Some studies have been completed to date; others are in
progress or planned for the future.
Beginning in 2006, the U.S. Department of Defense, in its attempt to reduce hospital
infections among injured soldiers in Iraq and Afghanistan, began to provide funding to
evaluate the potential role that copper touch surfaces might play in reducing bacterial
35
contamination that cause infections in military-operated healthcare facilities (Chapter
XVII). Results from these studies will be directly transferable to all healthcare facilities.
Due to all of these studies, we now have a much better understanding of copper‘s
antimicrobial properties. Many of the highlights of recent antimicrobial studies were
reported in the BioHealth Partnership (2007).
The microbes listed in Table 6.3 are of great concern to those involved in public health
including infectious disease professionals, the EPA, the U.S. Department of Defense, the
food industry and air quality experts. All of these pathogens (with the exception of Listeria
monocytogenes, a food-borne microorganism) infect patients at healthcare facilities though
various modes of transmission (i.e., touch, water, and air handling systems). Furthermore,
all of these pathogens either have been tested, are currently being tested, or will be tested
by researchers in the near future.
Table 6.3 — Target list of pathogens for antimicrobial experiments at healthcare
facilities. Presented at The Materials Science and Technology Conference, September 16-
20, 2007, Detroit, Michigan.
Organisms tested by researchers at the University of Southampton
Escherichia coli O157:H7
Listeria monocytogenes
Methicillin-resistant Staphylococcus aureus (MRSA)
Acinetobacter baumannii
Clostridium difficile
Influenza A
Adenovirus
Aspergillus niger
Aspergillus flavus
Aspergillus fumigatus
Fusarium culmonium
Fusarium oxysporium
Fusarium solani
Candida albicans
Penicillium chrysogenum
Vancomycin-resistant Enterococcus faecalis (VRE)
Organisms tested at the request of EPA for Public Health Product Registration
Staphylococcus aureus
Enterobacter aerogenes
Pseudomonas aeruginosa
Methicillin-resistant Staphylococcus aureus (MRSA)
Escherichia coli O157:H7
Organisms to be tested in the future
Klebsiella pneumoniae
Rotavirus
36
Subsequent chapters will show that carbon steel, stainless steel and aluminum surfaces
have no antimicrobial efficacy against common pathogens, such as E. coli O157, Listeria
monocytogenes, Salmonella sp., and Campylobacter sp. In fact, these microbes thrive and
can remain on stainless steel and aluminum surfaces for months.
We will also see that many different copper alloys were tested for their antimicrobial
properties, including high copper alloys, brasses, bronzes, copper-nickels and copper-
nickel-zincs. A strong case will be presented for the value of copper and copper alloys to
help control the presence, on environmental surfaces, of organisms that can cause
infections, such as Methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus
aureus, E. coli O157:H7, and others.
37
This chapter includes discussion of studies and test results showing, in some cases,
effective kill rates in time periods less than two hours. This information is provided
for background purposes. The shorter time periods should not be cited in relation to
the marketing of antimicrobial copper alloys in the U.S. Antimicrobial claims for
copper alloys are restricted, at this time, to claims of 99.9% bacterial kill within two
hours.
VII
The Case for Using Copper Touch Surfaces to Kill
E. coli in Healthcare Facilities
The promising results of testing to demonstrate copper‘s efficacy in inactivating microbes
prompted Keevil et al., (2000) to investigate copper‘s ability to inhibit verocytotoxigenic
Escherichia coli (VTEC) O157, also known as E. coli O157:H7. This bacterium is potent,
highly infectious, and is, perhaps, the best-known ACDP (Advisory Committee on
Dangerous Pathogens, UK) Hazard Group 3 foodborne and waterborne pathogen.
The bacterium produces potent toxins that cause diarrhea, severe aches and nausea in
infected persons. Symptoms of severe infections include hemolytic colitis (bloody
diarrhea), hemolytic uremic syndrome (kidney disease), and death. Children up to 14 years
of age, the elderly and immunocompromised individuals are at the greatest risk of incurring
the most severe symptoms.
E. coli O157:H7 infections have become a serious public health issue in the past three
decades. Cases of E. coli in the US have more than doubled from 1,667 cases in 1995 to
4,341 cases in 2000. In 2006, an E. coli outbreak from contaminated spinach infected 187
people, causing illnesses and three deaths (FDA, October 2, 2006).
While the incidence of E. coli infection is most often associated with the consumption of
contaminated food, the microbe has an uncanny ability to survive for long periods of time
and can be easily transmitted in healthcare facilities via direct contact with hands or on the
surfaces of medical devices, handrails, poles, floors, etc.
Copper Alloys Kill E. coli O157:H7; Stainless Steel Does Not
Recent studies have shown that copper alloys have strong bactericidal effects on E. coli
O157:H7 compared with stainless steel (Wilks and Keevil, 2003b; Michels, Wilks, Noyce,
and Keevil 2005; Wilks, Michels, Keevil, 2005). Whereas E. coli is able to survive for
several weeks on stainless steel, over 99.9% of the microbes are killed after just 1–2 hours
on copper.
38
Results of E. coli O157:H7 inactivation on C11000, a metal alloy containing 99.9% copper,
were published by Michels, Wilks, Noyce and Keevil (2005). The pathogens were rapidly
and almost completely killed (over 99.9% within two hours) (Figure 7.1). At 4°C, over
99.9% of E. coli O157:H7 were killed within 270 minutes. At 20°C, over 99.9% of E. coli
O157:H7 were killed within 90 minutes.
Figure 7.1 — E. coli O157:H7 viability on copper alloy C11000 surfaces showing an
almost complete (over 99.9%) kill of the pathogen on copper within 90 minutes at
20°C and within 270 minutes at 4°C. Source: Michels, et al., (2005)
Wilks, Michels, and Keevil (2005) also published results of E. coli O157:H7 death on a
variety of copper alloys, including four alloys (C10200, C11000, C18080, and C19700)
containing 99%–100% copper (Figure 7.2). At room temperature, the alloys began to kill
the pathogen within minutes, and near-zero counts were achieved within 75–90 minutes
representing a 7-log kill. At chilled temperatures, the inactivation process took about an
hour longer: practically all of the pathogens were completely dead within 180–270 minutes.
Despite the ―clean‖ look of stainless steel, no significant reduction in the amount of viable
E. coli O157:H7 was detected after 270 minutes (Figure 7.3). This leaves a pool of
pathogens as a potential source of cross-contamination.
39
Figure 7.2 — The Survival of Escherichia coli O157:H7 on different copper alloy
surfaces at room (top) and refrigeration temperatures. Source: Wilks, Michels, Keevil
(2005)
40
Figure 7.3 – E. coli O157:H7 viability on stainless steel (S30400) showing no
signifciant reduction in viable organisms after 270 minutes. Source: Wilks, Michels,
Keevil (2005)
Evaluation of Antimicrobial Efficacy of Various Copper Alloys for Medical and
Housekeeping Surfaces in Healthcare Facilities
Researchers are interested in quantifying the antimicrobial activity of a variety of copper
alloys. Doing so will offer product designers a range of mechanical and aesthetic properties
from which to fabricate copper alloy equipment, making these products more economical.
For this reason, Michels, Wilks and Keevil (2003, 2004) and Wilks, Michels, Keevil (2005)
conducted studies to examine the bactericidal properties of 25 different copper alloys
against E. coli O157:H7 (Table 7.1). The objective of these studies was to identify those
alloys that provide the best combination of antimicrobial activity, corrosion/oxidation
resistance, and fabrication properties.
As expected, copper‘s antibacterial effect was found to be intrinsic in all of the copper
alloys tested (Table 7.2). As in previous studies (Keevil et al. 2000; Maule and Keevil,
2000), no antibacterial properties were observed on stainless steel (UNS S30400).
1.00E+00
1.00E+02
1.00E+04
1.00E+06
1.00E+08
1.00E+10
0 60 120 180 240 300 360
Ba
cte
ria
Co
un
t (p
er
ml.)
Time (minutes)
E.coli Viability on an Alloy S30400 Surface
20 ºC
41
Table 7.1 — Nominal alloy compositions (weight, %)
Alloy UNS No. Cu Zn Sn Ni Al Mn Fe Cr P Si Ti Mg
Copper
C10200 100
C11000 100
C18080 99 0.1 0.5 0.1
C19700 99 0.7 0.3 0.1
Brass
C21000 95 5
C22000 90 10
C23000 85 15
C24000 80 20
C26000 70 30
Y90* 78 12 3 7
Bronze
C51000 95 5 0.2
C61500 90 2 8
C63800 95 3 2
C65500 97 1 3
C66300 86 10 2 2
C68800 74 23 3
Cu-Ni
C70250 96 3 0.7 0.2
C70600 89 10 1
C71000 79 21
C71300 75 25
C71500 70 30
C72900 77 8 15
Cu-Ni-Zn
C73500 72 10 18
C75200 65 17 18
C77000 55 27 18
Stainless Steel
S30400 0 8 74 18
Plastic
Polyethylene* 0
*no UNS number
Source: Michels, Wilks, Keevil (2004) and CDA Standard Designations for Wrought and
Cast Copper Alloys
Also, in confirmation with earlier studies (Keevil et al., 2000; Maule and Keevil, 2000), the
rate of drop-off of E. coli O157:H7 on the copper alloys was faster at room temperature
than at chill temperature.
It is interesting to note that, for the most part, the bacterial kill rate of copper alloys
increased with increasing copper content of the alloy (Michels et al., 2003, 2004). This is
42
further evidence of copper‘s intrinsic antibacterial properties, which is expected to pave the
way for the use of various copper alloys as hygienic materials in many applications.
Table 7.2 — Elapsed time of initial bacteria count drop-off and for near-zero bacteria
count. Elapsed Time (minutes) at 20°C Elapsed Time (minutes) at 4°C
Alloy UNS No. % Cu Rep Initial Drop-off Zero Count Rep Initial Drop-off Zero Count
Copper
C10200 100 5 45 75 4 90 180
C11000 100 6 75 90 4 180 270
C18080 99 5 45 75 3 180 270
C19700 99 5 45 75 4 90 180
Brass
C21000 95 5 60 90 3 90 180
C22000 90 3 45 60 4 75 180
C22000* 90 2 90 105
C23000 85 5 30 60 not tested not tested
C24000 80 4 60 75 4 270 360
C24000* 80 2 90 105
C26000 70 3 90 120 3 not seen not reached
C26000* 70 2 180 270
Y90** 78 5 90 120 3 180 270
Bronze
C51000 95 5 60 105 3 180 270
C61500 90 4 105 180 3 not seen not reached
C63800 95 5 60 90 3 90 180
C65500 97 5 45 65 3 90 270
C68800 74 4 120 270 3 not seen not reached
Cu-Ni
C70250 96 5 90 105 4 90 270
C70600 89 5 90 105 4 180 360
C71000 79 5 90 120 3 not seen not reached
C71300 75 4 75 120 3 270 360
C71500 70 4 105 not reached 3 not seen not reached
C72900 77 5 120 360 3 not seen not reached
Cu-Ni-Zn
C73500 72 5 60 90 3 not seen not reached
C75200 65 6 90 105 4 not seen not reached
C77000 55 4 90 not reached 3 not seen not reached
Stainless Steel
S30400 0 6** not seen not reached 2 not seen not reached
Plastic
Polyethylene* 0 3 not seen not reached not tested not tested
*no UNS number **consists of 2 for 270 minutes, 2 for 48 hours and 2 for 28 days
Source: Michels, Wilks, Keevil (2004)
43
Results on Pure Copper Alloys
As demonstrated in Table 7.2, all four of the 99%–100% pure copper samples were
effectively bactericidal at room and chill temperatures within a very short period of time
(i.e., within 75–90 minutes at 20ºC; within 180–270 minutes at 4ºC).
Figure 7.4 illustrates that at 20ºC, the E. coli O157:H7 count decreased by ½ log within the
first 45 minutes on UNS C10200 (a 99.95% copper alloy). Within the next 45 minutes, the
bacterial count rapidly dropped to near-zero. All four of the 99%–99.95% coppers
(C10200, C11000, C18080, and C19700) exhibited similar behaviors.
Figure 7.4 — E. coli O157:H7 Viability at 20°C and 4°C on Alloy UNS C10200
Copper Surfaces. Source: Michels, et al., (2005)
Results on Brasses
The brasses also demonstrated bactericidal properties, but within a somewhat longer time
frame than pure copper. This is in confirmation with results from Keevil et al., (2000) and
Maule and Keevil (2000). All nine brasses were almost completely (over 99.9%)
bactericidal at 20ºC, with timeframes for a ―near zero count‖ (death of practically all
bacteria) ranging from within 60–270 minutes. Many of the brasses were almost
completely bactericidal at 4ºC, with timeframes for a ―near-zero count‖ ranging from 180–
360 minutes. As an example, the viability of E. coli on brass alloy C22000 is illustrated in
Figure 7.5.
In the past, brass was commonly used for doorknobs and door push plates. The efficacy
studies on brasses summarized here indicate that it would be worthwhile to reconsider
installing brass doorknobs and push plates to reduce the incidence of bacterial
contamination in healthcare and other environments.
1.00E+00
1.00E+02
1.00E+04
1.00E+06
1.00E+08
1.00E+10
0 60 120 180 240 300 360
Bac
teri
a C
ou
nt
(pe
r m
l.)
Time (minutes)
E.coli Viability on an Alloy C10200 Surface
20 ºC 4 ºC
44
Figure 7.5 — E. coli O157:H7 Viability at 20C and 4C on Brass Alloy UNS C22000
Surfaces. (Note: There were five replications of this test. The secondary peaks are
anomalies related to the number of replicates and times at which bacteria counts were
measured. These secondary peaks do not represent a return to life and subsequent bacteria
growth.) Source: Michels, et al., (2004)
Results on Bronzes
Six alloys of bronze were examined for their antimicrobial efficacies. The rate of microbial
death varied from within 50–270 minutes at 20ºC, and from 180–270 minutes at 4ºC. Two
of the six bronze alloys were unable to kill over 99.9% of bacteria at chill temperatures.
The death rates of E. coli on various bronze alloys at 20ºC are illustrated in Figure 7.6.
Results on Copper-Nickel Alloys The six alloys comprising the copper-nickel group demonstrated a more predictable
antimicrobial efficacy pattern compared to the brasses and bronzes (Figure 7.7.) The kill
rate of E. coli O157 on the copper-nickel alloys clearly increased with increasing copper
content. However, two of the more corrosion-resistant alloys, C71500 (70% copper) and
C72900 (77% copper), were found to be somewhat slower than expected in killing the
microbe. Despite not achieving a complete kill, C71500 achieved a 4-log drop within the
six-hour test. This represents a 99.99% reduction in the number of live organisms. Among
this group of alloys, zero bacterial counts at room temperature were achieved after 105–360
minutes for five of the alloys. At the chill temperature, near-zero bacterial counts ranged
from 270–360 minutes for three of the alloys.
45
Figure 7.6 — E. coli O157:H7 Viability at 20C on Surfaces of Six Bronze Alloys
Source: Michels et al., (2004)
Figure 7.7— E. coli O157:H7 Viability at 20C on Surfaces of Six Copper-Nickel
Alloys. Source: Wilks, Michels, Keevil, (2005)
46
Results on Copper-Nickel-Zincs For the copper-nickel-zinc alloy group (also known as nickel-silver alloys because of their
silver color), the rate of microbial kill on these surfaces increased with increasing copper
content — just as with the copper-nickel alloys (Figure 7.8). Near-zero bacterial counts at
room temperature were achieved within 90–105 minutes for two of the alloys. However, at
the chill temperature, near-zero bacterial counts were not observed for this group of alloys.
Figure 7.8— Decrease in bacterial numbers with exposure time on copper-nickel-zinc
(nickel-silver) family alloys at 20°C (top) and 4°C. Source: Wilks, Michels, Keevil,
(2005)
47
A summary graph of the bactericidal efficacy of the 25 different copper alloys as a function
of copper content (Cu%) is depicted in Figure 7.9. The trend lines indicate that the
bactericidal efficacy of the various alloys increases with increasing temperature and
increasing copper content.
Figure 7.9 — Time at which practically no viable bacteria are detected at 20C and
4C on 25 copper alloys. Source: Wilks, Michels, Keevil (2005)
Tarnishing Does Not Reduce Antimicrobial Effectiveness of Copper Against E. coli
Michels (2005), in a presentation to the American Foundry Society, reported that tarnished
copper alloy surfaces were at least as effective against E. coli bacteria as bright, cleaned
copper alloy surfaces. At 20°C, the E. coli count on tarnished copper alloy C19700
(containing 99% Cu) dropped from approximately 1x107.5
microbes to 1x102.2
microbes
within 60 minutes, a decline of more than 99.9% (Figure 7.10, next page). On a tarnished
surface of C22000, (containing 90% Cu) the viability of E. coli dropped from 1x107.5
microbes to 1x104 microbes in 60 minutes, still a respectable decline (Figure 7.12).
The drop-off rates for both tarnished and clean C22000 were somewhat slower than for the
higher-copper alloy, C19700, presumably because of the lower copper content of C22000.
Since the drop-off on both materials is substantial, these results suggest that tarnish does
not impair the antimicrobial efficacy of copper alloys.
48
Results from Michels, Wilks, Noyce, and Keevil (2005) for alloy C77000 were later
compared with those of C19700 and C22000 regarding their inactivation efficiencies on
bright and tarnished surfaces (Figure 7.12). This illustration further confirms that
tarnishing does not reduce the antimicrobial effectiveness of copper.
The mechanisms responsible for the enhanced antimicrobial efficacy of tarnished copper
alloy surfaces are not understood at this time. It can be postulated that ionic copper is more
readily released on tarnished surfaces, but this has not been evaluated.
It is suggested that future experiments be conducted to determine whether there is an actual
advantage, in terms of antimicrobial efficacy, in tarnished copper surfaces.
Figure 7.10 — E. coli O157:H7 counts on a tarnished (T) copper alloy (C19700,
containing 99% Cu) dropped by more than 99.9% within 60 minutes at 20°C, initially
outpacing the efficacy of the clean (B) surface. Source: Michels (2005)
E. coli O157:H7 Remains Viable for Weeks on Stainless Steel
Unlike copper alloys, stainless steel (S30400) did not exhibit bactericidal properties at all
(Figure 7.13). Stainless steel, one of the most common touch surface materials in the
healthcare industry, allowed toxic E. coli O157:H7 to remain viable for the entire duration
of the study. Furthermore, a near-zero bacterial count was not observed on stainless steel
after 28 days.
Michels (2006) presents epifluorescence photographs (Figure 7.14) clearly illustrating that
E. coli O157:H7 is almost completely killed on copper alloy C10200 after 90 minutes at
49
20C; whereas, a substantial number of pathogens remain after the same time interval on
stainless steel S30400.
Figure 7.11 — E. coli O157:H7 counts dropped faster initially on tarnished surfaces of
copper alloy C22000 (containing 90% Cu) than on a bright, clean surface of the same
alloy Source: Michels (2005)
Figure 7.12 — E. coli O157:H7 viability on bright and tarnished alloy C19700,
C22000, and C77000 surfaces at 20°C. Source: Michels et al., (2005).
50
Figure 7.13 — Long-term viability of E. coli O157:H7 after 28 Days at 20C and 4C
on S30400 Stainless Steel Surface. Source: Wilks, Michels, Keevil (2005)
Stainless steel has often been selected as the most appropriate surface material because it
has poor adhesion characteristics (Merritt et al., 2000; Cookson et al., 2002) and can easily
be cleaned. However, as shown in the current studies, E. coli O157:H7 can survive for
extended periods of time when dried onto stainless steel surfaces. This means that a
potential contamination risk could occur if a stainless steel surface is not adequately
cleaned.
Silver-Containing Coatings Do Not Kill E. coli Bacteria
Silver has been known to be an antimicrobial material for many centuries. Several firms are
currently promoting the antimicrobial benefits of proprietary silver-based coating
technologies. However, when Michels, Noyce, Wilks, and Keevil (2005) evaluated a
commercial silver-containing antimicrobial coating on the surface of stainless steel alloy
S30400, only a four-log drop in bacterial count was observed after two days at 20C
(Figure 7.15). This was less than the 5-log drop observed on uncoated S30400 after two
days. (See Chapter XIII for more detailed discussions about the antimicrobial properties
of silver and tests conducted on proprietary, silver-containing antimicrobial coating
technologies).
51
Figure 7.14 — Epifluorescence photographs of E. coli O157:H7 demonstrate that the
pathogen is completely killed on copper alloy C10200 after 90 minutes at 20C (b).
There are a substantial number of pathogens on stainless steel S30400 (a) after the
same time interval. Source: Michels (2006)
Polyethylene Does Not Kill E. coli
An antibacterial efficacy examination was also conducted on polyethylene surfaces. Figure
7.16 clearly demonstrates that neither polyethylene nor stainless steel can kill E. coli
O157:H7 bacteria.
The results of these studies indicate that since stainless steel and polyethylene do not have
intrinsic antimicrobial properties, and silver-coated stainless steels are not effective under
typical environmental conditions, surfaces made from these materials are unable to contain
the spread of E. coli O157:H7 via cross-contamination. Alternatively, the intrinsic
antimicrobial properties of copper alloys has the potential to begin killing the toxic E. coli
O157:H7 pathogen immediately after contact, achieving a 99.9% reduction within two
hours according to laboratory testing.
a
bbaa
bbbb
bb
52
Figure 7.15 — E. coli viability at room and chill temperatures on a stainless steel
surface with an Agion®-containing coating. Source: Michels et al., (2005)
Figure 7.16 — E. coli O157:H7 viability at 20C on surfaces of alloy S30400 and on
Polyethylene, indicating that neither of these materials can kill the pathogen to any
significant degree within 4½—6 hours. Source: Michels et al., (2005)
53
As discussed in Chapter IV, healthcare facilities are not always properly cleaned, often
due to financial considerations. Consequently, the incidence of infection from cross-
contamination is significant. Therefore, as the research presented in this chapter shows,
added protection from an antimicrobial copper touch surface could be a worthwhile
supplement to hygienic measures.
For these reasons, it is recommended that the use of antimicrobial copper alloy touch
surfaces may be able to supplement the hygienic procedures at healthcare facilities and
provide an extra measure of protection. Use of these antimicrobial surfaces offers infection
control programs an additional weapon.
54
This chapter includes discussion of studies and test results showing, in some cases,
effective kill rates in time periods less than two hours. This information is provided
for background purposes, but the shorter time periods should not be cited in relation
to the marketing of antimicrobial copper alloys in the U.S. Antimicrobial claims for
copper alloys are restricted, at this time, to claims of 99.9% bacterial kill within two
hours.
VIII
The Case for Using Copper Surfaces to Kill Methicillin-resistant
Staphylococcus aureus (MRSA) In Healthcare Facilities
Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to all b-lactam antibiotics
because its mecA gene encodes the low-affinity penicillin-binding protein (Uger, 2003;
Mulligan et. al., 1993). MRSA was first isolated in England in 1961 (NCTC 10442). Its
prevalence declined in the 1970s, but the pathogen reemerged in the 1980s as epidemic
MRSA (EMRSA) (Hiramatsu, 1995; Ayliffe et al., 1999).
The first epidemic strain of MRSA, designated EMRSA-1, was recognized in 1981 and
continued to cause outbreaks in hospitals until the late 1980s (Marples and Cooke, 1985;
O‘Neill et al., 2001).
EMRSA strains initially seemed to be confined to outbreaks in one region, but the isolates
that emerged in the 1990s (EMRSA-15 and -16) caused outbreaks of infection and
colonization in hospitals in many regions (Cox et al., 1995). EMRSA-15 and -16 proved to
be highly transmissible and durable, and consequently gained a reputation as ―super‖
EMRSA (Cookson, 1997). To date, EMRSA-15 and -16 are the most prevalent strains in
the U.K. and have also been found in other European countries and the U.S. (Murchan et
al., 2004).
Copper Surfaces Kill Hospital-borne MRSA; Stainless Steel Does Not
Kuhn‘s (1983) preliminary observations about the antimicrobial properties of copper were
confirmed two decades later by Hosokawa and Kamiya (2002), who studied
Staphylococcus aureus populations on stainless steel door handles at a 759-bed facility in
Ube, Japan. Despite the hospital‘s good hygienic policies (including hand washing by
healthcare staff before and after contact with patients), stainless steel door handles on 53
out of 196 rooms (27%) were contaminated by MSSA (Methicillin-susceptible
Staphylococcus aureus) and/or MRSA. One in five door handles (19%) exhibited live
pathogens in rooms with MRSA-infected patients. This high incidence of live toxic
microorganisms on stainless steel door handle surfaces led the researchers to conclude that
―extensive‖ contamination of MSSA and MRSA existed at the hospital.
55
These findings supported the work of Talon (1999), who suspected that door handles
frequently used by hospital staff may be ―a secondary reservoir of MSSA and MRSA
contamination.‖
To reduce the rate of S. aureus infection in hospital environments, Bright et al. (2003)
understood the benefits of coating stainless steel surfaces with antimicrobial agents. This
team of researchers prepared two antibacterial formulations — a silver-copper powder
containing 3.1% silver plus 5.4% copper, and an alternative powder containing 2.5% silver
and 14% zinc. Both formulations removed approximately the same amount of bacteria
within 1–4 hours (Table 8.1).
Control 2.3%Ag 3.1%Ag +
5.4% Cu
2.5% Ag +
14% Zn
Inoculum 4.2x106 4.2x10
6 4.2x10
6 4.2x10
6
1 h 2.1x106 4.6x10
5 3.9x10
5 4.8x10
5
4 h 1.5x106 4.1x10
5 3.8x10
5 3.8x10
5
24 h 1.0x106 3.8x10
4 6.8x10
2 1.0x10
1
Table 8.1 — Reduction of S. aureus in zeolite powder amended with metal ions.
Source: Bright et al. (2003)
While it is worthwhile to note that copper (and silver) coatings on stainless steel exhibit
antimicrobial properties, the question remains regarding how to maintain the antimicrobial
efficacy of these coatings over time. Since antimicrobial coatings may wear off from
routine cleaning and regular use, a better alternative from an antimicrobial viewpoint would
be to use pure copper or copper alloy materials as touch surfaces instead of copper coatings
on stainless steel or other materials. It is expected that pure copper and copper alloy
materials should exhibit antimicrobial properties indefinitely over time.
Positive results from the studies mentioned above set the stage for a more comprehensive
approach to evaluating the antimicrobial efficacy of copper on MRSA. In 2004, a research
team from the University of Southampton, UK, successfully demonstrated that copper, in
fact, does inhibit MRSA (Noyce and Keevil, 2004). This finding was considered to be of
extreme importance to those concerned with hospital-acquired MRSA infections.
The research team compared the survival rates of MRSA on stainless steel (the most
commonly used metal in healthcare facilities) and on various copper alloys (Figure 8.1).
The findings were dramatic:
- At room temperature, MRSA was able to persist and remain viable in dried deposits
on stainless steel (S30400) for periods up to 72 hours (3 days).
56
- On copper alloys — C19700 (99% copper), C24000 (80% copper), and C77000
(55% copper) — significant reductions in viability were achieved after 1.5 hours,
3.0 hours and 4.5 hours, respectively.
- Faster antimicrobial efficacies are associated with higher copper content of the
alloys. Hence, MRSA is killed faster on 99% copper (C19700) than on 80% copper
(C24000), and faster on 80% copper than on 55% copper (C77000).
- The high copper alloy (C19700) killed the bacteria almost completely (over 99.9%)
after 90 minutes.
- Yellow brass (C24000) killed the bacteria completely after 270 minutes.
Figure 8.1 — Survival times of Methicillin-resistant Staphylococcus aureus on three
copper alloys and stainless steel (S30400) at room temperature. Source: Noyce and
Keevil (2004)
C19700 (99% copper) limited survival time to 1.5 hours. C24000 (80% copper) showed a
significant reduction after 3 hours and were almost completely killed after 4.5 hours.
C77000 (55% copper) showed significant and continuing reduction after 4.5 hours.
Survival time on stainless steel continued beyond 72 hours.
The results of this experiment led the research team to conclude that the contemporary use
of stainless steel for work surfaces and door furniture in hospital environments is
potentially exacerbating an already critical situation regarding MRSA transmission and
1.00E+00
1.00E+02
1.00E+04
1.00E+06
1.00E+08
0 60 120 180 240 300 360
Bac
teri
a C
ou
nt
(pe
r m
l.)
Time (minutes)
MRSA Viability on Copper Alloys & Stainless Steel at
20°C
C19700 C24000 C77000 S30400
57
infection. The team strongly believes that MRSA that cause infections could be reduced by
using copper alloys for touch surfaces in hospitals.
―MRSA infections in hospitals are pretty rife and out of control,‖ said Noyce in a statement
to the BBC News (July 5, 2004). ―The main mechanism of transfer is through cross-
contamination on work surfaces and contact surfaces, such as door handles and push plates.
If you changed some of these surfaces to copper-based alloys, these bacteria would be dead
in 90 minutes.‖
Noyce advised hospitals to switch materials from stainless steel to copper alloys in critical
care areas where patients are at greatest risk for being infected.
Figure 8.2 — Effect on MRSA viability during a 6-hour exposure to stainless steel
S30400 and copper alloys C77000, C24000 and C19700 at 4°C. Source: Noyce and
Keevil (2004)
Noyce and Keevil (2004) also conducted the same experiment at chill temperatures (Figure
8.2). Pure copper alloy C19700 was able to produce a 3-log drop (approximately 50% of
the microbial population) in MRSA count after three hours of exposure at 4ºC. Since the
antimicrobial efficacy of pure copper is not as compelling at chill temperatures as at room
temperatures, further vigilance is required in cold storage areas.
Bacterial drops on stainless steel and alloys made with 55% and 80% copper were
insignificant within six hours at chill temperatures. These alloys were deemed to be
ineffective at 4ºC.
1.00E+00
1.00E+02
1.00E+04
1.00E+06
1.00E+08
0 60 120 180 240 300 360
Bac
teri
a C
ou
nt
(pe
r m
l.)
Time (minutes)
MRSA Viability on Copper Alloys & Stainless Steel at 4°C
C19700 C24000 C77000 S30400
58
The ―Irony‖ of the Iron Alloy, Stainless Steel: Cleaning Is Necessary but Insufficient
Against MRSA
The irony of the iron alloy, stainless steel, is that it is used for its ability to be regularly
cleaned without displaying unwanted corrosion. However, French et al. (2004) have shown
conclusively that environmental cleaning after discharge of an infectious patient is
ineffective in eradicating MRSA. In their experiment, 74% of environmental swabs yielded
MRSA before cleaning. After cleaning, 66% of environmental swabs still carried the
MRSA pathogen.
Combating MRSA on Touch Surfaces: Copper vs. Non-copper Proprietary
Antimicrobial Products
Research has been conducted at the University of Southampton to compare the
antimicrobial efficacies of copper and several non-copper proprietary coating products to
kill MRSA (Keevil and Noyce, Michels et al. 2009). Figure 8.3 illustrates that, at 20ºC,
neither the tested triclosan based product, nor the two silver-containing based antimicrobial
treatments (Ag-A and Ag-B) exhibit meaningful efficacy against MRSA. As expected,
stainless steel S30400 also did not exhibit any antimicrobial efficacy. On the copper alloy
C11000, however, the drop-off in MRSA organisms is dramatic and almost complete (over
99.9% kill) within 75 minutes.
Figure 8.3 — Effects of copper vs. selection of antimicrobial coating products on
MRSA at 20°C. Source: Michels et al. (2009)
1
10
100
1,000
10,000
100,000
1,000,000
10,000,000
100,000,000
0 50 100 150 200 250 300 350
Co
lon
y F
orm
ing
Un
its
pe
r Sa
mp
le
Time (mins)
Stainless Steel Copper Ag-B Ag-A Triclosan
59
Copper Surfaces Kill Lower Concentrations of MRSA Faster
Noyce and Keevil were also interested in evaluating the effect of reducing the inoculum
size of MRSA on total kill time when exposed to copper. These results can be seen in
Figure 8.4. When the inoculum size was reduced to 1,000 CFU per coupon, the total time
for a near-complete kill was only 15 minutes. This is a very significant result, given that the
amount of contamination often found on environmental surfaces is often at this or lower
levels. However, 45 minutes was still required to kill over 99.9% of a concentration of both
10,000 and 100,000 CFUs per coupon, while 60 minutes was required to kill over 99.9% of
concentrations of 1,000,000 and 10,000,000 CFUs per coupon.
Figure 8.4 — The Kill Rate of Copper Alloy C11000 (99.9% copper) Related to
Inoculum Size. Source: Unpublished research by Keevil and Noyce. A similar data set on
copper alloy C19700 (99% copper) was published by Noyce and Keevil in 2006.
Please note that EPA registration approvals specify that copper alloys kill more than
99.9% of MRSA within two hours. Statements of kill rates within faster time frames
have not been approved by the EPA. All promotional materials developed for the U.S.
must conform to the approved language. Statements that are inconsistent with
product registration approvals are unlawful.
MRSA ( NCTC 10442) on C11000 at 20°C
1.E+00
1.E+01
1.E+02
1.E+03
1.E+04
1.E+05
1.E+06
1.E+07
1.E+08
0 15 30 45 60
Time (mins)
107 106 105 104 103 10 7
10 6
10 5
10 4
10 3
Co
lon
y F
orm
ing
Un
its
per
Co
up
on
60
Chapter Summary
- Clearly, the evidence suggests the need for more passive preventative measures
with regard to reducing MRSA effectively on commonly touched surfaces.
- Neither stainless steel nor proprietary non-copper products, such as silver-
containing antimicrobial coatings, nor triclosan-based antimicrobial treatments, kill
MRSA to any significant degree at typical indoor temperature and humidity
conditions.
- Copper alloys kill lower concentrations of MRSA faster
- Based on the results presented in this chapter, the utilization of copper alloys holds
promise for being an effective, passive approach to eliminating MRSA
contamination on environmental surfaces. Potential healthcare facilities that can
benefit from the use of copper alloys include hospitals, clinics, physician‘s
examination rooms, nursing homes, dental offices, long-term care facilities and
more.
- Non-healthcare related public spaces where copper alloys may be beneficial in
reducing MRSA pathogens on frequently touched surfaces include schools, public
buildings, shopping malls, hotels, gyms, prisons, mass transit systems, airports and
cruise ships.
61
*U.S. EPA-approved testing demonstrates antimicrobial effectiveness of copper alloys
against only the following organisms: Staphylococcus aureus, Enterobacter aerogenes,
Escherichia coli O157:H7, Pseudomonas aeruginosa, and Methicillin-resistant
Staphylococcus aureus. Efficacy against Clostridium difficile has not been proven by
EPA-approved testing. Promotional materials developed for the U.S. must conform to
EPA product registrations. Please see the EPA Approved Master Label (Appendix
XX) for approved language.
IX
The Case for Using Copper Touch Surfaces to Kill
Clostridium difficile in Healthcare Facilities
Clostridium difficile is a major cause of potentially life-threatening disease, including
nosocomial diarrheal infections, especially in developed countries (Drumford 2009). C.
difficile is currently a leading hospital-acquired infection in the U.K. (Health Protection
Agency, Surveillance of Healthcare Associated Infections Report 2007), and rivals MRSA
as the most common organism to cause hospital acquired infections in the U.S. (McDonald
et. al. 2006). It is responsible for a series of intestinal health complications, often referred
to collectively as Clostridium difficile Associated Disease (CDAD).
C. difficile infections, severity of disease, and death rates have been increasing in recent
years (McDonald et. al. 2006, Redelings et. al. 2007, and Siegel et. al. 2007).
Hospitalizations due to CDAD cause heavy financial burdens. CDAD is estimated to
increase patient hospitalization costs by $3,669-7,234, an increase of 54% compared to
those without CDAD (Kyne et. al. 2002, Wilcox et al. 1996). Length of stay is estimated to
increase by 3.6 to 21.3 days (Kyne et. al. 2002, Wilcox et al. 1996). Within the U.S., the
cost of CDAD has been estimated at $3.2 billion per year (O‘Brien et. al. 2007).
C. difficile is an anaerobic bacterium capable of forming an endospore. An endospore is a
tough, dormant, non-reproductive structure that forms within the vegetative cell. Its
primary function is to ensure the survival of the bacterium through long periods of
environmental stress. Upon exposure to favorable conditions, the endospore can be
activated and form a fully functional vegetative cell. Endospores are resistant to heat,
drying, and a variety of disinfectants. Because of this, C. difficile endospores can survive
for up to five months on surfaces (Kim et. al. 1981). The pathogen is frequently transmitted
by the hands healthcare workers throughout the hospital environment. Due to its highly
resilient nature, most common hospital grade disinfectants do not kill C. difficile
endospores. In fact, the only hospital disinfectant approved by the U.S. Environmental
Protection Agency as effective against this organism is the bleach formulation sold by the
Clorox company (Source: http://cloroxprofessional.com/cdiff/), Clorox Commercial
Solutions Germicidal Bleach®.
62
Antimicrobial Efficacy of Copper and Copper Alloys Versus Clostridium difficile
The antimicrobial efficacy of various copper alloys against Clostridium difficile was
recently evaluated by Weaver et al (2008). Weaver investigated the viability of C. difficile
spores and vegetative cells on the following copper alloys: C11000 (99.9% copper),
C51000 (95% copper), C70600 (90% copper), C26000 (70% copper), and C75200 (65%
copper). Stainless steel (S30400) was used as the experimental control.
Viability was assessed by utilizing viability dyes. This process for detecting and
enumerating viable bacterial cells is a useful alternative to culturing techniques. Traditional
culturing techniques have proven to be lacking as pathogenic bacteria are often found in a
Viable But Non-Culturable state in the environment (VBNC). Bacteria in the VBNC state
are capable of producing infections. Viability dyes allow for direct visualization of
metabolic activity in bacterial cells.
Results demonstrated that copper alloys significantly reduce the viability of both C. difficile
spores and vegetative cells. The concentration of vegetative cells and spores inoculated
onto the various coupons was approximately 900,000. On C11000, after 1 hour only 33
viable cells remained. Near total kill was observed after 3 hours (3 viable cells remained).
On C51000, after 3 hours total kill was nearly achieved, only 3 viable cells remained. On
C70600, only 3 viable cells remained after 5 hours. The kill rate was slightly slower on
C26000, 26 viable cells were detected after 24 hours. Near total kill was achieved after 48
hours (3 viable cells remained). On C75200, only 3 viable cells were detected after one
hour. The results are summarized on Figure 9.1.
On stainless steel the story is different. No reduction in viable organisms was observed
after 72 hours (3 days) of exposure. Moreover, when the exposure time was increased to
168 hours (one week), still no significant reduction was observed. In fact, the number of
total cells increased after 24 hours.
Traditional culturing methods were also used to evaluate the viability of both C. difficile
spores and vegetative cells. The results were only significantly different than those
obtained through viability dye analysis on alloys C26000 and C75200. Further research is
recommended if one wishes to consider utilizing copper alloys with less than 70% copper
to combat C. difficile spore contamination.
63
Figure 9.1 ─ Viability of C. difficile spores and total vegetative cells on various copper
alloys and stainless steel. Source: Weaver et. al. (2008)
1.E+00
1.E+01
1.E+02
1.E+03
1.E+04
1.E+05
1.E+06
1.E+07
1.E+08
0 10 20 30 40 50 60 70 80
Via
ble
Ce
lls p
er
Co
up
on
Time (hours)
C11000 (99.9% copper) C26000 (70% copper)
C51000 (95% copper) C75200 (65% copper)
C70600 (90% copper) S30400 (Stainless Steel)
64
*U.S. EPA-approved testing demonstrates antimicrobial effectiveness of copper alloys
against only the following organisms: Staphylococcus aureus, Enterobacter aerogenes,
Escherichia coli O157:H7, Pseudomonas aeruginosa, and Methicillin-resistant
Staphylococcus aureus. Efficacy against fungi has not been proven by EPA-approved
testing. Promotional materials developed for the U.S. must conform to EPA product
registrations. Please see the EPA Approved Master Label (Appendix XX) for
approved language.
X
The Case for Using Copper Surfaces to Kill or Inhibit
Fungal* Contamination in Healthcare Facilities
Copper‘s antimicrobial efficacy against pathogenic bacteria is well documented. However,
other microorganisms such as viruses and fungi (mold) can also cause infections, especially
in immune-compromised patients in healthcare facilities.
Antimicrobial Experiments with Various Fungi on Copper Alloys and Aluminum
Weaver et al., (2009) catalogues data regarding the antifungal properties of copper
challenged with a host of pathogenic fungal species. Tested organisms known to cause
infections include: Aspergillus spp., Fusarium spp., Penicillium chrysogenum, Aspergillus
niger and Candida albicans. The antifungal ability of copper was compared to that of
aluminum.
Data reported by Weaver et al., indicate an increased die-off of fungal spores on copper
surfaces compared with aluminum (Figure 10.1). This suggests that using copper
components would result in fewer available spores. Aluminum shows no meaningful
reduction in spores over the testing period. Similar results are expected on other materials
that do not posses antimicrobial activity. Weaver et al., also demonstrate that copper
inhibits the growth of Aspergillus niger, while aluminum does not (Figure 10.2).
Laboratory research investigating the antifungal properties of copper alloys is ongoing.
Field and laboratory studies through U.S. Department of Defense-funded trials (see
Chapter XVII) investigating copper‘s antifungal properties in actual-use conditions are
under way. More studies are recommended to quantify the importance of substituting
copper alloys for non-antimicrobial materials to reduce fungal surface-contamination in
healthcare facilities.
65
a b
c d
e f
Figure 10.1 — A. niger spores after 7 days exposure on copper (C11000) (a) and
aluminium (b); A. flavus after 4 days exposure on copper (c) and aluminium (d); and
A. fumigatus after 4 days exposure on copper (e) and aluminium (f) assessed using
epifluorescence microscopy. After the exposure time, 50 μL FUN-1 (Invitrogen) stain
was pipetted over surface of the coupon and incubated in the dark at 22 (±2)ºC for 2
hours. After incubation, coupons were tipped to remove excess stain and washed with
filter-sterile deionised water. Coupons were air dried in the dark before viewing
under epifluorescence microscope at 400x magnification. Spores or hyphae stained
orange to red are metabolically active, and those remaining green to yellow are not
active. Source: Weaver (2009)
66
a b
Figure 10.2 — Inhibition of A. niger growth on copper (a) and aluminium (b) coupons
after 10 days. Spore suspensions of A. niger (100 µL) were spread over PDA plates,
and coupons of copper and aluminium were placed onto the surface. Plates were
incubated at 22 (±2)ºC for 10 days. Growth occurred on the aluminium coupons;
whereas, growth was inhibited on and around the copper coupon. Source: Weaver
(2009)
67
*U.S. EPA-approved testing demonstrates antimicrobial effectiveness of copper alloys
against only the following organisms: Staphylococcus aureus, Enterobacter aerogenes,
Escherichia coli O157:H7, Pseudomonas aeruginosa, and Methicillin-resistant
Staphylococcus aureus. Efficacy against Adenovirus has not been proven by EPA-
approved testing. Promotional materials developed for the U.S. must conform to EPA
product registrations. Please see the EPA Approved Master Label (Appendix XX) for
approved language.
XI
The Case for Using Copper Surfaces to Inactivate
Adenovirus* in Healthcare Facilities
Adenovirus is a group of viruses that infect the tissue lining membranes of the respiratory
and urinary tracts, eyes, and intestines. Adenoviruses account for about 10% of acute
respiratory infections in children. These viruses are a frequent cause of diarrhea.
In a recent study, two million active adenovirus particles were inoculated onto copper
(C11000) and stainless steel (Figure 11.1). Within 1 hour, copper killed 1,500,000
infectious virus particles, or 75% of the total number of viruses inoculated onto the
material. Within six hours, 99.999% of the adenovirus particles were inactivated on copper.
During this same period, 50% of the infectious adenovirus particles (1 million particles)
survived on stainless steel. After 24 hours, one-half million particles survived on stainless
steel.
Once again, this study advocates the potential importance of using copper alloys instead of
stainless steel for touch surfaces in healthcare environments. More research is necessary to
determine whether copper alloys can reduce bioloading of adenovirus particles in
healthcare environments.
68
Figure 11.1 — Epifluorescent photographs show that copper inactivates 99.999% of
Adenovirus particles within 6 hours. On stainless steel, 50% of the infectious particles
survive within the same period. Source: Unpublished research by Keevil and Noyce.
69
*U.S. EPA-approved testing demonstrates antimicrobial effectiveness of copper alloys
against only the following organisms: Staphylococcus aureus, Enterobacter aerogenes,
Escherichia coli O157:H7, Pseudomonas aeruginosa, and Methicillin-resistant
Staphylococcus aureus. Efficacy against influenza A has not been proven by EPA-
approved testing. Promotional materials developed for the U.S. must conform to EPA
product registrations. Please see the EPA Approved Master Label (Appendix XX) for
approved language.
XII
The Case for Using Copper Touch Surfaces to Inactivate
Influenza A* in Healthcare Facilities
Influenza, commonly known as flu, is an infectious disease from a viral pathogen.
Influenza is caused by a virus different from the one that produces the common cold.
Symptoms of influenza are much more severe than the common cold. In humans,
symptoms include fever, sore throat, muscle pains, severe headache, coughing, weakness
and general discomfort. Influenza can cause pneumonia, which can be fatal, particularly in
young children and the elderly.
The flu spreads around the world in seasonal epidemics, killing millions of people in
pandemic years and hundreds of thousands in non-pandemic years. The U.S. Centers for
Disease Control and Prevention (CDC) estimates that 35 to 50 million Americans are
infected by the influenza virus during each flu season. This translates to approximately 25
percent of the population in the US. The flu can be deadly: approximately 20,000 to 40,000
Americans die every year from influenza infections (Source: National Institute of Allergy
and Infectious Disease).
Influenza is typically transmitted through the air by coughing or sneezing. This creates
aerosols that contain the virus. The disease can be transmitted by direct contact with
infected saliva, nasal secretions, feces, or blood. It can also be transmitted through contact
with contaminated hands (Goldmann, 2000) and surfaces (CDC, 2005). Infection control
measures for preventing and controlling influenza transmission in long-term care facilities
are summarized on the CDC‘s website:
www.cdc.gov/flu/professionals/infectioncontrol/longtermcare.htm.
Most influenza strains can be inactivated easily by disinfectants and detergents (Suarez et
al., 2003). However, if surfaces are not disinfected frequently, or if a surface is touched
before disinfection, the virus can spread via cross contamination.
For these reasons, the antiviral efficacy of copper alloy and stainless steel touch surfaces
with respect to influenza A virus particles was investigated by Noyce, Michels, and Keevil
(2007). The strain selected was A/PR/8/34 (H1N1), a strongly pathogenic strain that is
70
nearly identical to the H5N1 avian strain responsible for the much publicized avian flu and
very similar to the H1N1 swine flu virus.
Antimicrobial Experiments with Influenza A on Copper and Stainless Steel
Two million influenza A virus particles were inoculated onto copper and stainless steel and
incubated at room temperature (22°C). After incubation for one hour on copper, active
influenza A virus particles were reduced to 500,000, equivalent to a 75% reduction (Figure
12.1). After six hours on copper, there was a 4-log decrease (i.e., 99.999%) in active
influenza A virus particles: only 500 of the two million particles remained active.
Figure 12.1 — Fluorescent microscopy analysis photo of virus plates indicates a 75%
reduction of Influenza A after one hour of exposure on copper, and a 99.999%
reduction of the pathogen after six hours on copper. Many organisms are still alive on
stainless steel after 24 hours. Source: Noyce, Michels, Keevil (2007)
In comparison, one-half million active particles of influenza A are present on
the stainless steel sample after 24 hours of exposure.
71
These results indicate that the influenza A virus is rapidly inactivated on copper surfaces.
The results also confirm previous findings that the influenza A virus survives in large
numbers on stainless steel (Bean et al., 1982).
Barker et al. (2004) demonstrated that once surfaces are contaminated, fingers can transfer
virus particles to up to seven other clean surfaces. This observation suggests that materials
that possess innate antiviral properties could prevent subsequent cross-contamination.
The control of the influenza A virus, particularly with the emergence of potentially
pandemic strains, such as H1N1 swine flu and H5N1 avian flu, demands the highest level
of hygiene control, requiring multiple-barrier protection.
Simply replacing steel fittings with copper will not prevent the transmission of influenza.
However, the current study shows that copper surfaces may contribute to the number of
control barriers available to reduce the bioload of the virus, particularly in public facilities,
such as schools and healthcare facilities (Noyce, Michels, Keevil, 2007).
72
XIII
The Case Against Silver and Other Antimicrobial
Coating Technologies as Touch Surfaces to Combat
Cross-contamination in Healthcare Facilities
Silver: More Expensive than Copper; Efficacies of Antimicrobial Coating
Technologies Questionable
Ancient civilizations knew thousands of years ago that silver, like copper, prevented scum
from forming in drinking water jars. For example, Roman soldiers purified water with
silver coins. More recently, in the 19th
century, silver sutures were developed to reduce the
incidence of wound infections. For generations, to prevent blindness at childbirth caused by
gonorrhea in pregnant women, doctors put silver nitrate drops into the eyes of newborn
babies (Roylance, 2006).
But silver is an extremely expensive precious metal. In April 2009, silver traded at
approximately $13.00 per troy ounce. This is equivalent to almost $200 per pound. Copper
traded in the $2.00 per pound range on this same date. Hence, copper is typically about 1%
of the cost of silver.
Because of the high price of silver, it is economically unfeasible to use solid silver as
antimicrobial surfaces for most applications. For these reasons, manufacturers have
developed various proprietary technologies that incorporate small amounts of silver in
various materials. Despite antimicrobial claims by manufacturers, questions remain
regarding the efficacy of these materials (see Figure 13.1 and Table 13.1 and associated
text later in this chapter).
In 2007, silver-containing antimicrobial materials began to face environmental impact
concerns. The EPA decided to regulate ―antimicrobial silver‖ due to risks created by
leaching of metal ions from consumer and industrial products.
This chapter will explore, various silver-based antimicrobial technologies, antimicrobial
efficacy comparisons between silver-based technologies and copper, and regulations
proposed by the EPA to prevent environmental risks from silver leached from products
claiming to be ‖antimicrobial‖.
Antimicrobial Properties of Silver
Silver ions are believed to be released over a period of time and attack microbes from
several sites, where they interrupt critical microorganism functions and affect DNA. Some
researchers believe that the metal attacks as many as 10 sites on each microbe (Adams,
2006).
73
Silver ions readily bind to electron donor groups containing sulfur, oxygen and nitrogen, as
well as negatively charged groups such as phosphates and chlorides (Child 2005). A prime
molecular target for silver ions resides in cellular thiol (-SH) groups commonly found in
enzymes. The subsequent denaturation of the enzymes incapacitates the energy source of
the cell. The end result is the destruction of the microbe (Child, 2005). Silver may also bind
nonspecifically to cell surfaces where it can disrupt cellular membrane functions (Child,
2005; Roylance, 2006).
When silver nanoparticles come into contact with bacteria, they suppress the respiration of
bacteria. This, in turn, adversely affects bacteria‘s cellular metabolism and inhibits cell
growth (Adams, 2006).
Many antimicrobial silver-based technologies use silver oxide instead of metallic silver.
Once in the body, the molecule splits into a silver ion and an oxygen free radical, both of
which are toxic to microorganisms (Roylance (2006).
Silver-based Antimicrobial Technologies
A silver component was used in artificial heart valve tests. However, these tests were
terminated in 2001, after the silver caused adjacent heart cells to die. The dead cells also
loosened the valve, which was considered to be a health risk (Baltimore Sun, March 17,
2006).
More recently, silver ion-based antimicrobial technologies have been developed as an
alternative to massive silver. These technologies are based on a coating system that binds
silver ions into a fine ceramic powder (i.e., a zeolite). The silver ions are exchanged with
other ions when they are contacted with fluids (Child 2005). For long-term effectiveness
against bacteria, the silver-ions must be released slowly (Adams, 2006).
Target bacteria evaluated by silver-based coating developers include: Listeria
monocytogenes, Escherichia coli O157-H7, Salmonella enteriditis, Staphylococcus aureus
(resistant strain), Bacillus subtilis, Pseudomonas aeruginosa, Salmonella typhimurium,
Streptococcus faecalis, Legionella pneumophila, Vibrio parahaemolyticus, and
Enterobacter aerogenes. (Adams, 2006).
To date, silver-containing coating technologies have been used in the healthcare
environment in the following ways:
- Treated steel ducting and components in HVAC systems (Steele, 2001);
- Treated building materials (Myers, 2004), including laminates, floors (Duran, 1999;
Finelli et al., 2002);
- Wall paint, carpets, cubicle curtains, lockers, safety cabinets, bedpans, sack holders,
soap dispensers, keypads, medical devices (Duran, 1999; Finelli et al., 2002);
- Wound dressings and implants (Duran et al., 1994; Carrel, 1998).
74
Representative Antimicrobial Silver-Containing Coating Products
Several popular silver-containing coating products are introduced here. During this chapter
and as illustrated in Figure 13.1, evidence will be presented that antimicrobial efficacy
claims of these products are greatly exaggerated for use in real world environments (i.e.,
room temperatures and relative humidity).
- Agion Technologies (www.agion-tech.com ), in Wakefield, Mass., has developed a
proprietary silver and zinc zeolite technology for products in the consumer,
industrial and healthcare markets. Agion applies its antimicrobial powder coating to
metallic or plastic surfaces or impregnates plastic resins.
Carrier Corp., along with American Air Filters, produces a line of filters that use
Agion® antimicrobial coatings (Adams, 2006). Carrier evaluated the effectiveness
of the Agion antimicrobial coatings by testing a silver and zinc-containing zeolite
matrix. The coating, used on stainless steel, was tested for its antimicrobial
properties against E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, and
Listeria monocytogenes. Tests at Miami University found that the silver-zeolite
mixture reduced microbial colony-forming units from 84.536% to 99.999% after 4
hours of exposure, and from 99.992% to 100% after 24 hours of exposure. Some
reduction in effectiveness was noted after several washings, but the kill ratio topped
99% after 24 hours (Adams, 2006).
- BioCote Ltd. (http://www.biocote.com/protection.htm) offers its BioCote®
silver
antimicrobial technology that can be incorporated into powder paints, gel coats, wet
paints, lacquers, fabrics, papers and polymers. The company retained an
independent laboratory to evaluate the efficacy of its technology against MRSA, E.
coli, Legionella, Pseudomonas, Salmonella, Listeria, Campylobacter, S. aureus,
and Aspergillus niger. The company claims that levels of bacteria, mold, and fungi
are reduced by up to 99.9% over a 24-hour period on surfaces protected by Biocote.
- Nexxion Corp. has developed a thin silver oxide film technology for what it hopes
will be approved for antimicrobial medical devices, including catheters and
artificial knees. The company hopes to win FDA approval for combating
Staphylococcus aureus, E. coli and other bacteria (Roylance, 2006;
www.nonovip.com). Nexxion claims that its silver-containing coatings reduce
bacterial populations by factors of 100,000 to 1 million. According to the company,
the antimicrobial effects can be extended as long as 28 days, if needed, before the
body absorbs all the silver and eliminates it.
However, the technology may not work. Dr. Dennis G. Maki, Professor of Medicine
and head of infectious disease program at the University of Wisconsin Medical
School, said: "Although the silver ion is very bactericidal, maintaining it in its ionic
state is very difficult." (Baltimore Sun, September 28, 2007). Maki doesn‘t believe
there is enough silver ion to kill bacteria and there may not be enough time for the
75
silver ion to kill pathogens. As of this publication date, there is no record of FDA
approval for this product.
New EPA Regulations Will Restrict Silver-Based Nanotechnologies
While silver may be able to kill microbes, its antimicrobial efficacy is substantially higher
when processed into nanoparticles than in bulk form (Washington Post, November 23,
2006). Developments in the area of nanotechnology have enabled the use of antimicrobial
silver in plastics, fabrics, and coatings without the use of zeolites (Wagener et al., 2004).
Since nanosilver also can be easily incorporated into a variety of products, it has become
the most common type of nanomaterial marketed to consumers, according to the Project on
Emerging Nanotechnologies (Washington Post, November 23, 2006).
However, antibacterial silver nanotechnology has been a major concern to environmental
activist groups and the EPA, which decided in 2006 to regulate consumer items that
incorporate microscopic silver nanoparticles as pesticides. The agency cited anticipated
environmental risks of silver nanotechnologies with respect to beneficial bacteria, aquatic
organisms, and, possibly, to humans.
Research published in Toxicological Sciences and Toxicology In Vitro demonstrated that
nanosilver is highly toxic to mammalian germline stem cells, brain cells, and liver cells in
vitro (Friends of the Earth Nanotechnology Project, 2006; http://nano.foe.org.au/node/159).
In essence, the EPA ruling forbids companies to market products such as odor-eating
silver-containing shoe inserts without being able to prove, in a manner yet to be defined,
that the particles will not harm the environment (Nature, 2006).
According to a report in the Washington Post (November 23, 2006), one product in
particular, a clothes washer made by Samsung, has drawn EPA‘s attention because it
allegedly sanitizes clothes in cold water by releasing tiny charged silver particles into the
wash water. The silver particles are ultimately discharged into the environment, where they
may act as a pesticide.
In the Washington Post story, Chuck Weir, chairman of Tri-TAC, a technical advisory
group for wastewater treatment plants in California, said silver is highly toxic to aquatic
life at low concentrations and it bioaccumulates in some aquatic organisms, such as clams.
Samsung has withdrawn its Silver Nano™ washing machine in Sweden due to community
concerns. Friends of the Earth is now pressuring the company to withdraw this product in
Australia until peer-reviewed studies can demonstrate its safety to the environment and
human health (Friends of the Earth Nanotechnology Project, 2006;
http://nano.foe.org.au/node/159).
In addition to environmental impacts, there are financial impacts of silver nanotechnologies
on wastewater treatment plants. Operators are subject to penalties if water leaving their
stations is toxic to aquatic organisms.
76
Under the new EPA rules, any company wishing to sell a product that it claims will kill
germs by releasing nanosilver will first have to provide scientific evidence that the product
does not pose environmental and human health risks. The Natural Resources Defense
Council seeks to strengthen the language in this ruling because it still permits
manufacturing nanosilver products as long as the manufacturer does not make ―claims‖ as
to its antimicrobial benefits.
Other Competing Antimicrobial Coating Technologies
- Triclosan is an antibacterial agent that possesses antifungal and antiviral properties.
It is the active antimicrobial agent in various antimicrobial treatments, such as
Microban® and BioFresh™ (Glaser, 2004). Triclosan is most often used to kill
bacteria on the skin and other surfaces, although it sometimes is used to preserve
products against deterioration due to microbes (Lurie, Z., 2004). However, studies
have increasingly linked triclosan to a range of health and environmental effects,
from skin irritation, allergy susceptibility, bacterial antibiotic resistance, and dioxin
contamination to destruction of fragile aquatic ecosystems. A good description of
the benefits and risks of triclosan can be found in Glaser (2004).
Triclosan (http://www.microban.com/americas/?lang=en) is an EPA-registered
organic antimicrobial compound commonly found in household antibacterial soaps,
other personal care products, as well as industrial products, such as control panels,
switch touches, doors and worktops. According to the manufacturer of the triclosan-
based Microban, antimicrobial protection is built-in to products during
manufacturing to provide continuous protection for the useful lifetime of the
product. The continuous cleaning action of Microban, according to the
manufacturer, makes surfaces easier to clean and is especially useful in hard to
reach areas. However, as will be discussed later in this chapter and illustrated in
Figure 13.1, the antimicrobial efficacy claims for Microban are greatly exaggerated
in real world environments (i.e., normal room temperatures).
- The Component Hardware Group markets Saniguard® antimicrobial plumbing and
hardware products, including faucets, door handles, pull plates, grab bars, wash
sinks, floor drains and door lock sets, which the company claims inhibit the growth
of bacteria, mold and mildew for the entire life of these products. The active
ingredient (silver) is released on demand from the product from interactions with
pathogen-latent moisture. Target organisms claimed to be killed by Saniguard
include E. coli O157:H7, Staphylococcus, Salmonella, Legionella pneumophila,
Listeria, and norovirus.
- Goldshield™, marketed and distributed by NBS Technology, LLC, claims to
protect any physical surface from microbial contamination. According to the
company, it is a covalently bound antimicrobial which remains affixed to a surface
or textile material. Its core chemical formulation is 5% of 3-trihydroxysilyl
propyldimethyloctadecyl ammonium chloride, stabilized in water. It is a
commercial application of technology developed at Emory University.
77
Inappropriate Testing Standard for Antimicrobial Surface Products Results in
Inflated Claims by Manufacturers
As a general rule, technology developers and suppliers define coatings as ―antimicrobial‖
when they consistently kill greater than 99.9% of the bacteria encountered within a 24-hour
period, and if bacterial multiplication is inhibited.
With this in mind, some suppliers of antimicrobial products in years past made inflated
claims about the antimicrobial efficacy of their products. Subsequently, this issue was
addressed by the EPA under the Federal Insecticide Fungicide and Rodenticide Act
(FIFRA). Today, new antimicrobials must be registered with the EPA, which also closely
monitors effectiveness claims (Adams, 2006, see Chapter XVI).
Unfortunately, a major loophole exists regarding efficacy testing standards, and therefore,
claims for products tested by that standard.
Today, most suppliers test the effectiveness of their coatings through independent
laboratories that employ a Japanese international standard, called JIS Z 2801:2000, to
assess antimicrobial efficacy (Adams, 2006). The problem with the standard is that tests are
conducted under a plastic film at 35ºC and at a relative humidity greater than 90%. These
are extreme and inappropriate environmental conditions for real world environmental needs
— far from room temperature (20ºC) and normal humidity conditions. In fact, many
materials that would not ordinarily exhibit any antimicrobial efficacy in ambient conditions
would exhibit efficacy under these test conditions.
Non-copper Antimicrobial Coating Touch Surface Technologies Do Not Work In
Healthcare Environments
Because there is a long history of inflated claims by manufacturers of proprietary
antimicrobial touch surface technologies and because of the inappropriate environmental
conditions (35ºC and at least 90% relative humidity) of the JIS Z 2801:2000 standard, an
independent investigation was conducted to evaluate whether these products had any
antimicrobial efficacy at temperatures that were more representative of healthcare
environments.
Research was conducted at the University of Southampton to compare the antimicrobial
efficacies of copper and several non-copper proprietary products to kill MRSA (Keevil and
Noyce, unpublished data, 2007). Figure 13.1 clearly illustrates that at 20ºC, C11000
copper killed MRSA dramatically and completely within 75 minutes. However, there was
essentially no antimicrobial efficacy on the two tested silver-ion based products, nor on the
plain stainless steel surface.
Despite efficacy claims made by the manufacturers of these proprietary antimicrobial
technologies, these products did not kill MRSA at room temperature. Among them, only
78
copper surfaces were found to be antimicrobial against MRSA in real life environments
representative of healthcare facilities.
Figure 13.1 — Effects of copper vs. selection of proprietary antimicrobial coating
products on MRSA at 20°C. Only copper is found to be antimicrobial against MRSA
in environments representative of those within healthcare facilities. Source: Michels et
al., 2009.
A separate study by Dr. Harold Michels tested the antimicrobial efficacy of various copper
alloys and a silver-containing coating on stainless against MRSA under the temperature
and humidity conditions prescribed by the JIS Z 2801 standard (35° C and >90% relative
humidity), and under temperature and humidity conditions typically found in indoor
facilities in the US (20° C and 20%–24% relative humidity). The coating product
incorporates silver ions in a zeolite carrier. The results of testing are summarized in Table
13.1.
At 90% relative humidity and 35°C, all of the materials achieved a greater than 6-log
reduction in the amount of viable MRSA. This is a reduction of more than 99.9999% of
viable MRSA. At 90% relative humidity and 20°C, similar results are obtained on all
materials. At 20% relative humidity and 35°C, a reduction greater than 5.5 logs (greater
than 99.999%) is observed on all copper alloys; however, on the coated stainless steel, the
results are strikingly different. No reduction of MRSA is achieved. The results at 24%
relative humidity and 20°C are very similar. A reduction greater than 5.9 log is achieved
1
10
100
1,000
10,000
100,000
1,000,000
10,000,000
100,000,000
0 50 100 150 200 250 300 350
Co
lon
y F
orm
ing
Un
its
per
Sam
ple
Time (mins)
Stainless Steel Copper Ag-B Ag-A
79
on all copper alloys, while the reduction on the coated stainless steel is less than 0.2 log
(less than 20%).
These results suggest that relative humidity plays an important role in the performance of
antimicrobial coatings with silver ions in a zeolite carrier. The validity of the JIS Z 2801
antimicrobial efficacy test as a standard for evaluating antimicrobial materials intended for
use at ambient conditions is also brought into question (Michels et al., 2009).
* High humidity and temperature test conditions of JIS Z 2801 standard
** Silver-containing coating. The silver ions are incorporated into a zeolite carrier.
Table 13.1 — Log-10 MRSA reduction on copper alloys and a silver-containing
coating on stainless steel as a function of temperature and relative humidity. Source:
Michels et al., (2009)
Further tests on the non-copper proprietary antimicrobial technologies are clearly
warranted, both with respect to MRSA as well as to all other pathogens of concern in
healthcare environments. Should the tests continue to confirm that the non-copper
proprietary technologies are indeed ―not antimicrobial,‖ it will be essential to communicate
these results to hospital administrators and purchasing agents — for patients may become
victims of false efficacy claims.
Materials >90% RH*
~35°C
>90% RH
~20°C
>20% RH
~35°C
>24% RH
~20°C
C11000: Copper >6.4 >6.1 >5.5 >5.9
C51000: Phosphor Bronze >6.4 >6.1 >5.5 >5.9
C70600: Cu-Ni >6.4 >6.1 >5.5 >5.9
C26000: Cartridge Brass >6.3 >6.1 >5.5 >5.9
C75200: Cu-Ni-Zn >6.4 >6.1 >5.5 >5.9
Ag-A** >6.4 5.5 0 <0.2
80
XIV
Dermal Effects of Copper
As part of the copper industry‘s diligence in evaluating copper as an effective antimicrobial
material for healthcare facilities, it is also incumbent upon the industry to demonstrate that
the repetitive touching of copper alloy surfaces does not exhibit adverse effects to human
skin.
Copper Is Essential in Maintaining and Improving Dermal Health
Copper is an essential nutrient needed to maintain human health, and it plays an important
role in improving and maintaining healthy skin.
Copper is an ingredient in lysyl oxidase, an enzyme that helps to form collagen and elastin
(Szauter et al., 2005). This copper-based enzyme improves skin strength and helps to
maintain a more youthful skin appearance. Another copper enzyme, copper-zinc
superoxide dismutase, is an antioxidant that has been demonstrated to neutralize damaging
free radicals (i.e., reactive oxygen species) (Uriu-Adams and Keen, 2005). A deficiency of
copper, in fact, can lead to hypo-pigmentation and increased skin sensitivity to sunlight
(Reish et al., 1995).
The antimicrobial properties of copper, in addition to the presence of copper in essential
enzymes, are actually important benefits in the metal‘s use for skin health. For example:
- Copper creams are used extensively in hospital burn units to help heal burns, treat
lesions and improve the healing of open wounds (Canapp et al., 2003).
- Since copper does not easily enter skin cells, researchers have developed peptides
(small proteins) to facilitate penetration of ―active copper‖ for clinical conditions.
- A copper-based topical drug, Antabuse (disulfiram), destroys melanoma cells and is
being evaluated as a potential treatment for skin cancer (Cen et al., 2004).
- Copper benzoates and salicylates, when applied to the skin, are used to treat skin
inflammation (Auer et al.,, 1990).
Dermal Contact with Copper Is Not Toxic
There are no studies to indicate that skin contact with copper is toxic. In fact, the American
Conference of Governmental and Industrial Hygienists does not provide a hazardous skin
notation rating for copper on cutaneous exposure as part of its Threshold Limit Value
(TLV) guidelines for occupational exposure (http://www.acgih.org/tlv/). A study of
cutaneous absorption of copper oxide and metallic copper as an ointment over a four-week
81
period found that there were no risks of systemic toxicity from dermal exposure (Gorter et
al., 2004; Hostynek and Maibach, 2006).
No Dermal Penetration by Copper
Many studies indicate that metallic copper and inorganic copper compounds do not
penetrate skin. In vitro experiments with human skin have shown that dermal absorption is
only 0.03% for contact with dry skin; for wet skin, dermal absorption is 0.3% (% of amount
applied to skin that penetrates skin during 24 hours of continuous contact (Cross et al.,
2006; Hostynek and Maibach, 2006).
Copper Is Not a Dermal Irritant; Dermal Hypersensitivities Extremely Rare
Skin irritations and hypersensitivities to copper are extremely rare (Karlberg et al., 1983).
Twelve animal studies show that copper has no irritating effect when the copper compound
is taped onto animal skin for at least 24 hours (Hostynek and Maibach, 2006). Immune
reactions to metallic copper within the general public have been extremely rare, especially
considering the large number of industrial workers in daily contact with the metal at
smelters and refineries around the world (Hostynek and Maibach, 2006).
Considering the widespread use of copper in coins and jewelry, reports of sensitization are
extremely rare (Hostynek and Maibach , 2006), and clinically relevant cases are even less
common. Where sensitization cases do exist, they are often due to cross-reactivity between
copper and other metals (Candura et al., 1999).
Studies in rodents indicate that copper may have anti-inflammatory effects (Dollwet et al.,
1981), and, while these beneficial effects have not been clinically demonstrated on humans,
societies in many parts of the world have worn copper bracelets and jewelry for centuries
because they believe metallic copper has anti-inflammatory effects.
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XV
Potential for Microbial Resistance to
Copper’s Antimicrobial Efficacy
It is well known that microbes have the ability to adapt to adverse conditions and threats,
such as antibiotics. Heavy antibiotic use in hospitals has in fact prompted the emergence of
multidrug-resistant ―superbugs.‖ However, scientists believe it is unlikely that exposure to
copper touch surfaces will breed copper-resistant bacterial strains.
There are several reasons for this. First, the kill rate of bacteria on copper surfaces is
extremely high (>99.9%), indicating that copper is disrupting cell function in several ways.
Since some of the mechanisms may be acting simultaneously, it is believed that they might
work together to reduce the ability of microorganisms to develop resistance to copper
(Michels et al., 2005).
Second, and equally important, the antimicrobial efficacy of copper is extremely fast —
usually within minutes to a few hours (Espirito Santo et al., 2008). The rapid death of
bacteria will not allow for resistance to develop since the cells do not have a chance to
develop a defense mechanism. Also, since there are virtually no survivors,
resistance/tolerance genes cannot be passed on.
Less than 0.01% of microbes survive on a copper surface after 24 hours of exposure. In
unpublished testing, performed by CDA, these ―survivors‖ were later inoculated on a
copper surface again. Upon re-exposure to copper, they did not survive. This indicates that
the microbes had not developed a resistance to copper surfaces. It is believed that these
organisms survived on the copper surface originally because they were not in direct contact
with the copper. They were inoculated on the copper surface after a significant amount of
organic material (and other organisms) had been deposited on the copper surface as
indicated in the Continuous Reduction of Bacterial Contaminants EPA test protocol (see
Chapter XVI).
Copper-resistant bacterial strains reported in the literature are resistant to high copper
levels in moist growth media, or moist organic material such as soil. However, known
copper-resistance or copper-tolerance mechanisms (Bender and Cooksey 1987; Odermatt et
al., 1992; Brown et al. 1995) do not prevent the rapid death of microorganisms on dry
copper surfaces (Espirito Santo et al., 2008; Elguindi et al., 2009). This is because bacterial
death on a copper surface is probably caused by a different mechanism, such as damage to
the cell or organism‘s outer membrane.
Copper is not genotoxic (does not affect the integrity of an organism‘s genetic material,
Cross et al., 2006; Macomber et al., 2007). It is known that copper does not damage DNA
in E. coli. Copper can be cytotoxic at very high concentrations, as, for example, when
encountered by a microorganism on a dry copper surface. This means that, on a copper
surface, the bacterium dies without any change in its genetic material.
83
Copper has been used since the Bronze Age (since the 8th
millennium BC), often to keep
water clean (i.e., free from slime/scum). Despite the fact that copper has been around for
10,000 years, bacteria still cannot survive on its metallic surfaces. In contrast, resistance to
beta-lactam (penicillin-type) antibiotics became prevalent after only 30 years of use.
While existing evidence indicates that microbes will not be resistant to copper as an
antimicrobial material, experimental and empirical studies need to be conducted so it can
be further confirmed.
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XVI
U.S. EPA Registration of Antimicrobial Copper Touch Surfaces
After decades of independent laboratory testing, followed by years of additional rigorous
testing under its prescribed protocols, in Februray 2008 the U.S. Environmental Protection
Agency approved the first set of registrations of copper alloys as ―antimicrobial materials
with public health claims.‖
The registration enables producers of copper-based products to promote the inherent ability
of copper, brass and bronze to kill harmful, potentially deadly bacteria.
This registration, supported by extensive EPA-mandated antimicrobial efficacy testing,
indicates that copper alloy products kill more than 99.9% of the following disease-causing
bacteria within two hours, when cleaned regularly (to be free or dirt or grime that may
impede contact with the copper surface):
- Escherichia coli O157:H7, a foodborne pathogen associated with large-scale food
recalls.
- Methicillin-resistant Staphylococcus aureus (MRSA), one of the most virulent
strains of antibiotic-resistant bacteria and a common culprit of hospital- and
community-acquired infections.
- Staphylococcus aureus, the most common of all bacterial staphylococcus (i.e.,
Staph) infections that cause life-threatening disease, including pneumonia and
meningitis.
- Enterobacter aerogenes, a pathogenic bacterium commonly found in hospitals that
causes opportunistic skin infections and impacts other body tissues.
- Pseudomonas aeruginosa, a bacterium in immunocompromised individuals that
infects the pulmonary and urinary tracts, blood and skin.
Before the antimicrobial copper alloy registration was granted, only antimicrobial gases
liquids, sprays and concentrated powders were registered to make antimicrobial public
health claims. The most common of these products are sterilizers, disinfectants and
antiseptics. They are regulated by EPA under the Federal Insecticide, Fungicide and
Rodenticide Act (FIFRA).
Public Health vs. Non-Public Health Antimicrobial Claims
Several solid antimicrobial materials, including those that contain triclosan or silver-based
coatings (see Chapter XIII), have been granted an antimicrobial non-public health
85
registration, otherwise known as a ―Treated Article Exemption,‖ a special restricted-
provision registration under FIFRA. EPA grants Treated Article Exemptions only for
nonpublic health uses of a pesticide intended to protect or preserve treated articles.
Significantly, to obtain a non-public health registration, registrants need only demonstrate
that the substance will not cause unreasonable adverse effects to human health or the
environment; they do not have to demonstrate the antimicrobial efficacy of the
substance. Accordingly, for such ―treated articles,‖ EPA has not reviewed or approved
claims of efficacy beyond protection of the article itself from bacteria, mold or mildew that
can cause odors, deterioration or discoloration.
An example of a treated article is the addition of a fungicide to paints for the purpose of
preventing the development of mildew. In this application, the fungicide protects the paint,
but it does not protect people who touch the painted surface from microbes. For this reason,
manufacturers of fungicide paints are not legally permitted to make public health claims
(i.e., state that the product kills bacteria that may harm human health). Accordingly, this
type of restriction forbidding manufacturers to make public health claims applies to all
products granted Treated Article Exemptions.
Articles or products that claim to be effective in controlling infectious microorganisms,
such as E. coli, S. aureus, Salmonella sp. or Streptococcus sp., must attain a public health
product registration. These articles or products can then make a public health claim that
goes beyond the preservation of the treated article itself. EPA requires the submission of
efficacy data in support of the public health labeling claims and the patterns of use of the
product.
In this chapter, you will find summaries of U.S. FIFRA regulations, antimicrobial studies
mandated by EPA, and highlights of the EPA registration granted for antimicrobial copper
products.
Background on the Registration Process
The EPA, a federal government agency, is assigned responsibility for regulating
antimicrobial products. Regulations require the successful completion of a lengthy
registration process before products can be labeled ―antibacterial‖ and their public health
benefits promoted.
The EPA‘s Office of Pesticide Programs (OPP) manages the registration process for all
articles or products claiming to be effective in preventing, destroying, repelling or
mitigating pests. The OPP also regulates the distribution, sale and use of all types of
pesticides, including those intended to kill pathogens.
All pesticides marketed in the U.S. must be registered and properly labeled. Pesticides
intended to have a positive impact on human health, i.e., those that are allowed to make
―human health claims,‖ are also required to undergo exhaustive efficacy evaluations.
86
Penalties can be levied by the U.S. Government for noncompliance with FIFRA
regulations. EPA warns that pesticide-treated products not registered by the Agency must
not make public health claims, such as stating that the product ―fights germs‖ or ―provides
antibacterial protection‖ or ―controls fungus.‖ According to the EPA Guidance Document
PR 2000-1, the EPA will act ―quickly and decisively to prohibit sales of unregistered
products.‖ For additional information about FIFRA regulations summarized in the EPA
Guidance Document PR 2000-1, see: www.epa.gov/oppmsd1/PR_Notices.
CDA’s Leadership Role in the Registration of Copper and Copper Alloys as
Antimicrobial Materials
Published studies presented in Chapters II, VI, VII, VIII, IX, X, XI, and XII show that
several disease-causing species of bacteria begin to die on copper alloy surfaces in a matter
of minutes and over 99.9% are killed within two hours. However, to legally make such
public health claims, EPA requires thorough efficacy testing.
Efficacy studies must be reviewed and approved by EPA. The process is a major
investment in time and money.
On behalf of the copper industry, the U.S. Copper Development Association Inc. (CDA)
assumed the responsibility for evaluating and registering copper and its alloys with EPA.
EPA required studies for five different pathogens on five different representative copper
alloys using approved protocols at an EPA-approved, independent laboratory. The results,
summarized in this chapter, were a resounding success that culminated in the registration of
275 antimicrobial copper alloys with public health claims.
EPA Test Protocols for Copper
To help EPA determine the acceptability of copper as an antimicrobial material for various
product uses and for public health labeling claims, the Agency required submission of a
wide body of antimicrobial efficacy data according to three different test protocols:
- Efficacy as a Sanitizer: This test protocol measures surviving bacteria on alloy
surfaces after two hours. The protocol implemented for copper alloys followed the
Standard Test Method for Efficacy of Sanitizers Recommended for Inanimate Non-
Food-Contact Surfaces (ASTM E 1135-03).The length of time pathogens were
exposed to copper surfaces increased from five minutes to two hours. (Note that
despite the test name, due to the two hour time period for efficacy, copper alloys are
not approved as ―sanitizers‖ under the EPA registration.)
- Residual Self-Sanitizing Activity: This test protocol measures surviving bacteria on
alloy surfaces before and after six wet and dry wear cycles over 24 hours in a
standard wear apparatus. The test for copper alloys followed the EPA Protocol for
Residual Self-Sanitizing Activity of Dried Chemical Residues on Hard Nonporous
87
Surfaces. The exposure times between the pathogens and copper surfaces increased
from five minutes to two hours, and ―coated‖ antimicrobial surfaces were replaced
with solid copper alloy surfaces.
- Continuous Reduction of Bacterial Contamination: This test protocol measures the
number of bacteria that survive on a surface after it has been re-inoculated eight
times over a 24-hour period without intermediate cleaning or wiping. The test
method implemented for copper alloys was developed by CDA and EPA and was
designed to demonstrate that copper alloy surfaces could be effective after
numerous, sequential inoculations occur on ―touch‖ surfaces. The test protocol was
modeled after the Standard Test Method for Efficacy of Sanitizers Recommended
for Inanimate Non-Food-Contact Surfaces (ASTM E 1153-03). For this protocol, a
99% or greater efficacy was required to justify antimicrobial claims.
It is hoped that all test protocols developed jointly by the EPA and CDA (i.e., Efficacy as a
Sanitizer, Residual Self-Sanitizing Activity and Continuous Reduction of Bacterial
Contamination) will set new standards for evidenced-based validation of the antimicrobial
effectiveness for solid materials. By doing so, a meaningful and level playing field will be
maintained as efficacy determinations are made on other solid materials.
GLP Laboratories Ensure Data Integrity and Accuracy
All tests were performed by an approved Good Laboratory Practices (GLP) laboratory. Use
of GLP laboratories is required by EPA to ensure data integrity and accuracy.
GLP laboratories incorporate a system of management controls to guarantee the
consistency and reliability of results. These practices, established by the Organisation for
Economic Co-operation and Development (OECD), apply to nonclinical studies that assess
the safety of chemicals to man, animals and the environment.
An internationally accepted definition of GLP, excerpted from Wikipedia and based on
information provided by the Organization for Economic Co-operation and Development
(OECD), is as follows:
―GLP embodies a set of principles that provides a framework within which
laboratory studies are planned, performed, monitored, recorded, reported
and archived. These studies are undertaken to generate data by which the
hazards and risks to users, consumers and third parties, including the
environment, can be assessed for pharmaceuticals, agrochemicals,
cosmetics, food and feed additives and contaminants, novel foods and
biocides. GLP helps assure regulatory authorities that the data submitted
are a true reflection of the results obtained during the study and can
therefore be relied upon when making risk/safety assessments.‖
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Copper Alloys and Pathogens Evaluated for EPA
Independent GLP tests were conducted on the following five pathogens:
- Staphylococcus aureus
- Enterobacter aerogenes
- Escherichia coli O157:H7
- Pseudomonas aeruginosa
- Methicillin-resistant Staphylococcus aureus (MRSA)
Five copper alloys, each representing a major copper alloy family, were tested. The
nominal chemical compositions of these alloys, summarized in Table 16.1, range from
65% copper to 99.90% copper. The experimental control was UNS S30400 stainless steel,
a material widely used in food processing and healthcare applications. UNS S30400 does
not exhibit antimicrobial efficacy.
Alloy UNS Number Cu Zn Sn Ni Fe Cr P
C11000: Copper 99.90
C26000: Brass (cartridge brass) 70 30
C51000: Bronze (phosphor bronze) 95 5 0.2
C70600: Cu-Ni (copper nickel) 90 10
C75200: Cu-Ni-Zn (nickel silver) 65 17 18
S30400: Stainless Steel 8 74 18
Table 16.1 — Nominal Copper Alloy Compositions (by elemental weight %). Source:
Michels (2005)
Test Results
More than 3,000 copper alloy samples in 180 separate GLP tests were analyzed for the
EPA registration. The results for each test protocol, which were presented to the EPA, are
summarized in Table 16.2.
Table 16.2 presents the efficacy data for the copper alloys tested under the three protocols
described above. In 174 of the 180 tests, the bacteria count was reduced by more than
99.9%. In the remaining six tests (all under the most rigorous ―Continuous Reduction‖ test
protocol), the bacteria count was reduced by 99.3% to 99.9%.
Results for Efficacy of Copper Alloy Surfaces as a Sanitizer:
In this test protocol, a reduction in live bacteria greater than 99.9% was seen on copper
within two hours on all 60 tests. For example, Figure 16.1 illustrates the efficacy of copper
alloy surfaces as a sanitizer for Methicillin-resistant Staphylococcus aureus and
Enterobacter aerogenes. These efficacies are typical against all five microorganisms by all
five copper alloys.
89
Table 16.2 — Results of testing under three EPA test protocols demonstrate the
antimicrobial efficacy of copper alloys: efficacy as a sanitizer, residual self-sanitizing
activity, and continual reduction of bacterial contaminants. Source: Michels and
Anderson (2008)
Figure 16.1 — Typical data for efficacy of copper alloy surfaces as a sanitizer on
microorganisms tested for EPA. This table illustrates results with Staphylococcus aureus
(ATCC 6538) and Enterobacter aerogenes (ATCC 13048). Source: Michels and Anderson
(2008).
1.00E+00
1.00E+01
1.00E+02
1.00E+03
1.00E+04
1.00E+05
1.00E+06
1.00E+07
1.00E+08
1.00E+09
1.00E+10
Ba
cte
ria
Co
un
t (p
er
ml.)
Initial Concetration Viability on S304 Viability on C110
GLP RESULTS
S. Aureus E. aerogenes MRSA P. aeruginosa E. coli
O157:H7
Efficacy as a
Sanitizer
C110 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9
C510 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9
C706 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9
C260 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9
C752 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9
Residual Self-
Sanitizing
C110 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9
C510 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9
C706 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9
C260 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9
C752 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9
Continuous
Reduction of
Bacterial
Contaminants
C110 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9
C510 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 99.9 >99.9 >99.9 >99.9 >99.9
C706 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9
C260 >99.3 >99.7 99.7 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9
C752 >99.9 >99.6 >99.6 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9 >99.9
90
Residual Antimicrobial Efficacy of Copper Alloy C26000
4.68E+053.63E+05
2.40E+06
<3.98E+01 <5.37E+01
5.89E+06
<3.02E+01 <3.02E+01
1.00E+00
1.00E+01
1.00E+02
1.00E+03
1.00E+04
1.00E+05
1.00E+06
1.00E+07
1 4
Lo
g
Staphylococcus aureus control Staphylococcus aureus survivors per test carrier (lot 4237450)
Enterobacter aerogenes control Enterobacter aerogenes survivors per test carrier (lot 4237450)
Initial Final
Results for Residual Self-sanitizing Activity of Copper Alloy Surfaces:
In the Residual Self-Sanitizing test protocol, a reduction in live bacteria >99.9% was seen
on copper in all 60 tests. This surface remained effective in killing greater than 99.9% of
Staphylococcus aureus, Enterobacter aerogenes, Escherichia coli O157:H7 (ATCC
#35150), Methicillin-resistant Staphylococcus aureus (MRSA ATCC #33592), and
Pseudomonas aeruginosa (ATCC #15442) bacteria within two hours, even after repeated
wet and dry abrasion and recontamination over a 24-hour period. The results for
Staphylococcus aureus and Enterobacter aerogenes, which are representative of typical
data, are illustrated in Figure 16.2.
These results confirm that the antimicrobial efficacy of copper alloys is robust and durable.
Figure 16.2 — Residual antimicrobial efficacy of copper alloy C26000 after
inoculation of Staphylococcus aureus and Enterobacter aerogenes. Copper alloy C26000
performed just as well in the initial two hour antimicrobial efficacy test as it did after the
six wet and dry wear cycles. Source: Michels and Anderson (2008)
Results for Continuous Reduction of Bacterial Contamination on Copper Alloy Surfaces
In this test protocol, a reduction of >99.9% was achieved in 54 out of 60 tests. In many
tests, practically no survivors were observed at all. In five of the S. aureus tests, a reduction
of 99.3% was observed on one lot of C260, 99.7% on two lots of C260, and 99.6% on two
lots of C752. In the sixth test, MRSA on C70600, the reduction was 99.9%.
91
1.E+00
1.E+02
1.E+04
1.E+06
0 3 6 9 12 15 18 21 24Bac
teri
a C
ou
nt
(pe
r m
l.)
Time (hours)
Continuous Reduction of E. coli O157:H7 on C110
= Inoculation
Figure 16.3 demonstrates the efficacy of alloy C11000 against Escherichia coli O157:H7.
After each inoculation, more than 99.9% of the bacteria are killed within two hours. Figure
16.4 demonstrates the efficacy of alloy C11000 against MRSA. Even with survivors (last 3
drops) more than 99.9% of the bacteria are killed within two hours after each inoculation.
Similar results were achieved with all microbes on all five of the copper alloy surfaces.
A few MRSA survivors (Figure 16.4) were subsequently re-cultured and exposed to the
copper surface to determine whether or not a tolerance had developed. The re-cultured
organisms were killed within two hours.
Figure 16.3—Continuous reduction of E. coli O157:H7 on C11000 inoculated eight
times over a 24-hour period. Source: Michels and Anderson (2008)
These results for copper alloys can support claims on labels indicating that laboratory
testing shows that, when cleaned regularly:
- Copper alloy surfaces prevent the growth and build-up of Staphylococcus aureus,
Enterobacter aerogenes, Escherichia coli O157:H7, Methicillin-resistant
Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa bacteria within two
hours of exposure between routine cleaning and sanitization.
- Copper alloy surfaces continuously reduce bacterial contamination, achieving a
99.9% reduction within two hours of exposure.
92
- Copper alloy surfaces kill greater than 99.9% of bacteria within two hours, and
continue to kill 99% of bacteria even after repeated contamination.
Clearly, these results prove that the antimicrobial efficacy of copper alloys is consistent,
strong, enduring and reproducible.
Figure 16.4—Continuous reduction of MRSA on C11000 inoculated eight times over a
24-hour period. Source: Michels and Anderson 2008
EPA Registration of Antimicrobial Copper Alloys
The antimicrobial efficacy demonstrated by the five copper alloys against all five
pathogens in all three test protocols led the EPA Office of Pesticide Programs to approve a
public health product registration for 275 UNS-registered copper alloys.
EPA Health and Safety Assessment
Antimicrobial copper alloys are registered under the Federal Insecticide, Fungicide and
Rodenticide Act (FIFRA) no "unreasonable adverse effects" standard. The EPA has
determined that these products do not pose a risk to public health; they have been in use for
centuries, and there is no known harm from such use.
After consultation with the Association for Professionals in Infection Control and
Epidemiology (APIC) and the American Society for Healthcare Environmental Services
(ASHES), as well as a leading expert in the field, Dr. William A. Rutala, Ph.D., M.P.H.,
University of North Carolina (UNC) Health Care System and UNC School of Medicine),
the EPA concluded that the use of these products could provide a benefit as a supplement
to existing infection control measures.
1.00E+02
1.00E+03
1.00E+04
1.00E+05
1.00E+06
0 3 6 9 12 15 18 21 24
Bac
teri
a C
ou
nt
Time (hours)
Continuous Reduction of MRSA on Alloy C11000
= Inoculation
93
Registered Copper Alloys
275 UNS-registered copper alloys were originally approved by the EPA to be marketed as
antimicrobial materials. Seven additional alloys have since been registered and many more
will eventually be added. These contain a minimum of 60% copper by weight (nominally).
The alloys are registered as six separate groups according to their respective copper
content.
Group Copper % EPA Registration Number
I 95.2 to 99.99 82012-1
II 87.3 to 95.0 82012-2
III 78.1 to 87.09 82012-3
IV 68.2 to 77.5 82012-4
V 65.0 to 67.8 82012-5
VI 60.0 to 64.5 82012-6
Table 16.3 — Registered groups of antimicrobial copper alloys with their respective
ranges of copper content and EPA registration numbers.
A listing of the 282 registered copper alloys is provided in Appendix XXII.
Approved Claims
The following claims can be made when marketing EPA-registered antimicrobial copper
alloys.
Laboratory testing has shown that when cleaned regularly:
- Antimicrobial Copper Alloys continuously reduce bacterial* contamination,
achieving 99.9% reduction within two hours of exposure.
- Antimicrobial Copper Alloy surfaces kill greater than 99.9% of Gram-
negative and Gram-positive bacteria* within two hours of exposure.
- Antimicrobial Copper Alloy surfaces deliver continuous and ongoing
antibacterial* action, remaining effective in killing greater than 99% of
bacteria* within two hours.
- Antimicrobial Copper Alloys surfaces kill greater than 99.9% of bacteria*
within two hours, and continue to kill 99% of bacteria* even after repeated
contamination.
- Antimicrobial Copper Alloys surfaces help inhibit the buildup and growth of
bacteria* within two hours of exposure between routine cleaning and
sanitizing steps.
* Testing demonstrates effective antibacterial activity against Staphylococcus aureus,
Enterobacter aerogenes, Methicillin-resistant Staphylococcus aureus (MRSA), Escherichia
coli O157:H7, and Pseudomonas aeruginosa.
94
The registrations clearly state that ―antimicrobial copper alloys may be used in hospitals,
other healthcare facilities, and various public, commercial and residential buildings.‖
Product Stewardship
As a condition of registration, CDA agreed with EPA that responsible stewardship of
antimicrobial copper alloys is necessary, particularly given the unique antimicrobial
characteristics of these products. In particular, it is important for users to understand that
the registered copper alloys are a supplement to and not a substitute for standard infection
control practices, and that all current infection control practices, including those related to
cleaning and disinfection of environmental surfaces, must continue to be followed.
Antimicrobial copper alloys are intended to provide supplemental antimicrobial action in
between routine cleaning of environmental or touch surfaces in healthcare settings, as well
as in public buildings and the home. Users must also understand that in order for
antimicrobial copper alloys to remain effective, they cannot be coated in any way. For
these reasons, CDA has developed an outreach program for potential users to reinforce
these messages and to ensure a proper understanding of the potential role copper alloys
may play in an infection control program. The outreach program is being carried out by
CDA through written communications, a stewardship website
(www.antimicrobialcopperalloys.com), and through a Working Group, which meets to
expand educational efforts and address questions and concerns from the public and
infection control community.
Additionally, EPA has mandated that all advertising and marketing materials contain the
following statement in equal prominence as any antimicrobial claims made for the product:
The use of a Copper Alloy surface is a supplement to and not a substitute for
standard infection control practices; users must continue to follow all
current infection control practices, including those practices related to
cleaning and disinfection of environmental surfaces. The Copper Alloy
surface material has been shown to reduce microbial contamination, but it
does not necessarily prevent cross-contamination.
As has been noted throughout this document, any promotional materials developed for the
U.S. to support the sale of antimicrobial copper alloy products must be consistent with the
EPA registration and approved label language. Through the Product Stewardship program,
CDA has the responsibility of ensuring that these guidelines are followed by
manufacturers. Because of this, CDA must review and approve all promotional materials.
The complete Approved Product Label that must accompany all products for which
antimicrobial claims are made is found in Appendix XXI. Included in the label are
directions for use and approved uses for Antimicrobial Copper Alloy products.
More than 100 different potential product applications were cited in the registrations for
their potential public health benefits.
95
Chapter Summary
These are very exciting developments for the healthcare industry as well as the copper
industry. Copper alloys have attained a ground-breaking EPA registration for a solid
material. Copper alloys have been registered with EPA as Public Health Products.
Manufacturers that incorporate registered copper alloys into their products can now make
public health claims for those products.
To attain this registration, five copper alloys representing the major alloy families were
subjected to three rigorous tests to evaluate their antimicrobial efficacy. The alloys tested
were C11000, C51000, C70600, C26000, and C75200. A sixth alloy, C28000 was also later
tested. The tests evaluated the ability of the alloys to kill 99.9% of five organisms within
two hours, have residual self-sanitizing activity, and continuously reduce organisms after
repeat contaminations without cleaning. The five organisms tested were: Staphylococcus
aureus, Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa,
Enterobacter aerogenes, and Escherichia coli O157:H7. All testing was conducted in
Figure 16.5 — Scan of the official registration document for Antimicrobial Copper
Alloys Group II (Registration documents for the five groups are identical.)
96
accordance with the Organisation for Economic Co-operation and Development‘s Good
Laboratory Practice guidelines.
In total, over 3,000 copper alloy samples were tested. In 174 of the initial 180 tests, the
bacteria count was reduced by more than 99.9%. In the other six tests, the bacteria count
was reduced by 99.3 to 99.9%.
In total, 275 copper alloys were initially registered. The alloys were divided into five
groups according to their nominal copper content. A sixth group was also later registered.
The total number of registered alloys is now 282. These have a minimum nominal copper
concentration of 60%. Additional copper alloys will be added to the registration in the
future.
As a condition of registration set by EPA, CDA is responsible for the stewardship of
antimicrobial copper alloy products. CDA must ensure that manufacturers promote these
products in an appropriate manner. Manufacturers have to promote the proper use and care
of these products and must specifically emphasize that the use of these products is a
supplement and not a substitute for routine hygienic practices. CDA is currently
implementing an outreach program through written communications, a product stewardship
website, and through a Working Group which meets periodically to expand educational
efforts.
97
XVII
U.S. Department of Defense Funding for Antimicrobial Copper
Research and Other Hospital Trials
DoD Addresses Problem of Keeping Injured Soldiers Safe from Hospital-acquired
Infections
The U.S. Department of Defense (DoD) has vested interests in the potential for
antimicrobial copper surfaces to reduce hospital-acquired infections: thousands of enlisted
servicemen and servicewomen in the U.S. armed forces have been injured in recent
conflicts; a significant percentage of these casualties have contracted hospital-acquired
infections while convalescing. The situation among armed forces casualties is no different
from that of patients in the public sector, but DoD wants its injured soldiers returned home
without risks from infections.
Reports have been published that multidrug resistant infections have become commonplace
with injured troops in Iraq and Afghanistan (CBS News, September 30, 2007). The military
however, thought these infections were caused by obscure organisms found in desert soil.
Subsequent investigation determined that organisms less obscure, such as multidrug-
resistant Acinetobacter baumannii, were infecting service people and were also thriving in
emergency rooms, ICUs, and operating rooms at combat support hospitals.
Hospital-acquired Acinetobacter baumannii infected more than 700 soldiers in Iraq from
2003 until the beginning of 2007 (Wired, 2007). More than 70 patients at Walter Reed
Hospital eventually contracted Acinetobacter blood infections. Other infected patients and
pathogen carriers surfaced at Landstuhl, Germany; Bethesda, Maryland; and Balad Airbase,
an embarkation point for troops leaving Iraq. By early 2005, nearly one-third of wounded
soldiers admitted to the National Naval Medical Center had been infected by the bacteria
(Wired, 2007).
Until a few years ago, most strains of Acinetobacter baumannii could be treated with a
wide variety of drugs. Strains of Acinetobacter are now emerging that are resistant to most
many types of traditional treatments. According to a recent CDC study, the new multidrug-
resistant organisms are almost four times more deadly than older strains (Wired, 2007). The
bacteria have metastasized among institutions where medical personnel, students, families
and patients go back and forth to multiple medical centers.
Once Acinetobacter finds its way into a healthcare facility, it's hard to eradicate and easy to
pass along. Eradication requires many different simultaneous strategies and may take many
months to get under control, if it can be brought under control at all.
98
DoD Takes Initiative to Clean Up Its Hospitals and Healthcare Centers
This grave situation prompted the DoD to take the health matters of its injured personnel
into its own hands. The department decided to take the initiative to investigate effective
solutions to reduce hospital-acquired infections among its wounded personnel.
The Telemedicine and Advanced Technologies Research Center (TATRC) is a division of
the Army Medical Research and Materiel Command which operates a $1.5 billion annual
budget, 28% of which goes to its Military Infectious Disease Program (Internal Medicine
World Report, 2007). TATRC was granted funds by the United States Congress to evaluate
the antimicrobial effectiveness of copper, brass and bronze alloys. The Advanced
Technology Institute in Charleston, South Carolina, is coordinating the studies.
In September 2006, two five-year federal research programs were launched. The U.S.
government appropriations provided the copper industry‘s antimicrobial initiative with a
much welcomed boost, both in terms of financing as well as confidence in antimicrobial
copper research that has been conducted. Highlights of the programs are summarized here.
Clinical Trial #1: Copper Antimicrobial Research Program to Determine the Efficacy
of Copper Touch Surfaces to Mitigate Cross-contamination of Infectious Disease
This study will determine the degree to which copper, brass and bronze surfaces decrease
bacterial contamination by killing bacteria that frequently cause hospital-acquired
infections. Surfaces that are being manufactured with copper alloys for this study are
typically made with stainless steel or plastic, neither of which have demonstrated efficacy
in controlling pathogens.
Target surfaces identified for the hospital trials are listed in Table 17.1; six (marked by *)
have been chosen for full study in the trials. These surfaces will be manufactured from
copper alloys. Seven additional items (marked by #) have been identified by infection
control professionals as high priority items, but will not be included in the evaluations.
Three facilities were selected to conduct this study:
- Memorial Sloan-Kettering Cancer Center, New York, N.Y.
- The Medical University of South Carolina, Charleston, S.C.
- The Ralph H. Johnson VA Medical Center, Charleston, S.C.
-
The objectives of the study include the following:
1. Evaluation of infection rates. Since the most crucial question is whether reduced
bioloading translates into improved clinical conditions, the impact of copper touch
surfaces will be assessed for their ability to reduce microbial transmission from the
environment to hospital patients. Surveillance, statistical analyses, and molecular
biological analyses will be employed in this assessment.
99
Table 17.1—Target surfaces identified for hospital clinical trials in DoD-funded
copper antimicrobial surface study. Source: Unpublished information, Schmidt, M.,
MUSC (2006)
High-priority touch surface products identified for the hospital trials include:
- *Beds
- *IV poles
- *Input device (computer mice, touch screen monitor bezels)
- *Nurse call device
- *Tray tables
- *Chair arms
- #Keyboards
- #Faucet handles
- #Door handles
- #End table surfaces
- #Drawer pulls
- #Laundry hamper
- #Soap and alcohol dispensers
Personal items used by hospital staff considered for the clinical trials included:
- Pens
- Stethoscopes
- Pagers
- Cell phones
- Clipboards/notebooks/patient charts
Lower priority touch surface products considered for the clinical trials included:
- Nurse work tables
- Door push plates
- Telephone handsets
- Monitors
- Sink counters
- Glove dispensers
- Switch plates
- Plug ports (e.g., oxygen)
- Handles
- Fluid pumps
* Surfaces that were selected for copperization and enumeration.
# Surfaces that will not be copperized but on which the level of bacterial contamination
was initially enumerated.
100
2. Evaluation of patient immune response to copper touch surfaces in three
different clinical trials. Three separate clinical trials have been established to
measure whether copper touch surfaces decrease hospital-acquired infections
among patients as a function of immune strength. Studies will be implemented in
three different environments to decipher responses from patients with different
levels of immunity:
a. An intensive care unit, where severely ill patients with the highest
susceptibility to hospital-acquired infections reside;
b. A cancer ward, where patients are under less intensive care than in an ICU
but where their immune systems are nevertheless compromised; and
c. A gastrointestinal unit of a regular medical ward, where patients generally
have stronger immune responses than in an ICU or cancer ward.
3. Determining rates of infection on two pathogens of concern. MRSA and
vancomycin-resistant Enterococci (VRE) will be evaluated in the three clinical
settings. These microbes are among the most common in infected hospital patients
(Tenover and McDonald. 2005) and are of increasing concern to healthcare
administrators (Nordmann, P. 2004; Richet and Fournier, 2006; Wisplinghoff et al.,
2000). By determining the effectiveness of copper at reducing the burden of these
pathogens, the degree to which copper can lower environmental bioloading will be
estimated.
4. Data validation of EPA test results. EPA test results discussed in Chapter XVI
will be validated and reproduced in patient healthcare environments.
The first phase of the study will determine baseline microbial loads on surfaces in a clinical
setting. Those with the highest bioloads will be identified and replaced with components
made from antimicrobial copper.
For example, in the ICU at Memorial Sloan-Kettering Cancer Center items such as bed
rails and tray tables will be replaced with copper equivalents (The Star Ledger, August 28,
2007). Results of the Phase 1 study will establish control values from which the efficacy of
intervention with copper materials will be based.
During the second phase of this study, the impact of copper touch surfaces will be
measured for their ability to reduce levels of harmful microbes in a clinical setting. Testing
will be conducted on both copper and surfaces made from other materials to determine
whether the microbial bioloading has been reduced on surfaces made from copper.
The third phase of this study will measure the rate of acquisition and transfer of monitored
microorganisms from touch surfaces to patients and from patients to touch surfaces. This
will establish the effectiveness of copper touch surfaces to help reduce microbial transfer
among patients. Subjects will be monitored until discharged from ―copperized‖ and ―non-
copperized‖ rooms. Transmission will be determined from nasal and perirectal swabs taken
from patients.
101
Note that, regardless of the outcome of these clinical trials, EPA does not allow
antimicrobial products to make any claims related to the prevention of infections or
reduction in infection rates. In the United States, claims are limited to reducing the
level of bacteria that may cause infections.
A roadmap of the clinical trial is presented in Table 17.2.
Dr. Kent Sepkowitz, director of infection control at Memorial Sloan-Kettering Cancer
Center, said, "We need to look at all different ways of confronting this problem.‖
Sepkowitz believes that copper surfaces will prove to be a ―passive way of helping control
these organisms‖ and hopes people will ―see this as a way to cut down on these [bacteria
that cause] infections and adopt it as part of the solution.‖ Sepkowitz warns that while
copper will not replace good hygiene practices, it may nevertheless help to reduce bacterial
contamination associated with hospital-acquired infection (The Star Ledger, August 28,
2007).
Clinical Trial #2: Copper Air Quality Program
A second congressionally funded study, also under the aegis of TATRC, will compare the
antimicrobial efficacies of aluminum and copper heating, ventilating and air-conditioning
(HVAC) components, including cooling coils, heat exchange fins and drip pans (Internal
Medicine World Report, 2007). The pathogens of concern in this study will include both
bacteria and fungi that thrive in dark, damp HVAC environments.
The study will evaluate, within a pilot scale system, whether copper-finned heat exchangers
can reduce microorganisms that contaminate air-handling systems, cause unpleasant odors
and degrade system performance. The energy efficiency of these systems will also be
monitored. The all-copper systems are expected to perform much more efficiently due to
the combination of copper‘s antimicrobial properties, superior thermal conductivity and
corrosion resistance. The benefits of copper condensate drip pans versus aluminum drip
pans will also be evaluated.
The study is now underway at the University of South Carolina‘s Arnold School of Public
Health in Columbia, South Carolina. Simultaneous field trials are being performed in
certain barracks at the at the Fort Jackson military base in Ft. Jackson, South Carolina.
It is expected that the results of these field trials will demonstrate the antimicrobial benefits
of copper components in HVAC systems.
Note that as of November 11, 2009, EPA is reviewing an application to register
antimicrobial copper alloys for use in HVAC systems. This registration will be a non-
public health registration that allows claims to be made regarding protection of
HVAC system equipment from bacteria, mold and mildew that cause odors and
reduced system efficiency. Public health claims, including claims related to improved
indoor air quality, are not allowed.
102
Table 17.2—Roadmap of Clinical Trial #1 Copper Antimicrobial Research Program
funded by DoD.
103
Other Hospital Trials throughout the World
United Kingdom
A pilot study in the U.K. assessed the number of microorganisms on grab rails, water tap
handles, light switches, door push plates and copper-containing toilet seats, on a busy
medical ward at Selly Oak Hospital (part of the University Hospital Birmingham, NHS
Trust). The levels of bacterial contamination on their non-copper counterparts were also
assessed. The study found that the items made of copper and copper alloy harbored 90%-
100% less bacteria. These initial results were presented at the Interscience Conference on
Antimicrobial Agents and Chemotherapy (ICAAC) in Washington, D.C., 28th October
2008 (Lambert et. al., 2008).
Japan
In 2005, studies were conducted in the Dermatology Ward and in the Neonatal Intensive
Care Unit (NICU) at Kitasato University Hospital in Japan. Researchers there evaluated the
antimicrobial efficacy of copper on floors, sinks, push plates, showerheads and doorknobs
by comparing bacterial loads on these surfaces and on their non-copper counterparts. The
results demonstrated that copper and copper alloys have a strong antimicrobial effect while
the materials currently used for these surfaces do not (Sasahara et. al., 2007).
Other hospital trials evaluating the antimicrobial efficacy of copper and copper alloys are
currently underway in Germany, Chile and South Africa. It‘s anticipated that these trials
will continue to demonstrate that using copper alloy touch surfaces is an effective
supplement to infection control programs in healthcare facilities.
Chapter Summary
- The U.S. Department of Defense (DoD) is addressing the problem of trying to keep
its wounded soldiers safe from hospital-acquired infections.
- TATRC, a division of the U.S. Army, was granted funds by the U.S. Congress to
evaluate the antimicrobial effectiveness of copper, brass, and bronze alloys.
- The first federally funded study will evaluate the efficacy of copper to kill deadly
pathogens and reduce the availability of targeted microorganisms for transfer from
touch surfaces to patients, staff, and guests.
- Hospitals have been selected for these clinical trials.
- Touch surface products that are potential causes of cross-contamination are being
manufactured in copper alloys for testing in the clinical trials.
- A second federally funded study will evaluate the efficacy of copper to reduce
microbial contamination in HVAC systems. This study will compare microbial
104
contamination in HVAC systems made with copper components (cooling coils, heat
exchange fins, and drip pans) versus those made with aluminum components.
- It is expected that the results of the second clinical trial will prove that the
antimicrobial properties of copper can reduce microbial contamination that causes
odors and compromises the performance of HVAC systems.
- Hospital trials in the U.K. and Japan have demonstrated that a significant reduction
in bacterial contamination on environmental surfaces occurs on copper surfaces.
105
XVIII
Market Opportunities for Copper Touch Surfaces in
Healthcare Facilities
The antimicrobial evaluation process mandated by EPA and discussed in Chapter XVI
was completed on February 29, 2008. The ensuing registration enables manufacturers of
copper alloy products to make public claims that copper surfaces kill bacteria that cause
infections and impact public health . Clinical trials evaluating the efficacy of copper
surfaces to kill pathogens and reduce the levels of microbial contamination on
environmental touch surfaces in hospital settings are also underway in the U.S. and other
countries (Chapter XVII). The stage is being set to bring antimicrobial copper products to
market.
In this chapter, we will explore:
- Work surfaces and furniture/hardware retrofits made with copper alloys with the
potential to significantly reduce microbial contamination on environmental
surfaces.
- Proposed new applications for copper and copper alloys in health-related facilities.
- The call for stakeholders to develop copper-based antimicrobial products needed for
healthcare facilities.
- The need for stakeholders to ensure that beneficial copper-alloy products are
installed in hospitals around the country to help reduce the levels of bacterial
contamination that exist in hospitals and cause hospital-acquired infections.
Medical Equipment and Housekeeping Surfaces
Doorknobs, door handles and push plates are the easiest components to convert to copper
alloys, in retrofit and in new construction. They represent the most common contact
surfaces for patients, visitors and staffs. Stainless steel door handles and other external
hardware can be readily replaced with brass, bronze and copper materials. Because many
such items are currently manufactured as coated products, they would require minimal
retooling by manufacturers.
Doorknobs are perceived to be one of the more important touch surfaces in hospitals and
other health-related facilities, so it is not surprising that the earliest work on the
antimicrobial efficacies of touch materials was conducted on doorknobs. As mentioned
earlier in this paper:
- Kuhn (1983) discovered that stainless steel doorknobs do not to kill hospital-
acquired microbes, particularly E. coli, Staphylococcus aureus, Pseudomonas sp.,
106
and others. Copper and copper alloys, on the other hand, exhibit strong
antimicrobial effects against all of these pathogens. For these reasons, Kuhn
suggested that hospitals retain their old brassware, remove or plate stainless steel or
aluminum doorknobs and push plates or disinfect them every day to prevent the
spread of contaminants.
- Hosokawa and Kamiya (2002) found that stainless steel doorknobs offer a strong
viable pathway for MRSA and MSSA cross-contamination in the hospital
environment.
Faucets are also excellent environments for bacteria transmission because most faucets are
chrome plated. This provides the illusion of cleanliness. Changing faucet handles to copper
alloys will ensure that these items are actually 99.9% free of bacterial contamination.
Handles, spouts and other hardware are often supplied as chromium-plated finishes or as
stainless steel in hospitals and other institutional settings. These are worthy of replacing
with copper alloys. Copper grab bars in bathrooms offer another opportunity to improved
hygiene.
Hospital railings, stair railings, banisters, and especially bed rails are often broad-faced
with plastic coverings over steel structural support, or may be made with wood or plastic.
While items made from these materials may be aesthetically pleasing and easy to keep
clean, they do not offer the same antibacterial qualities as copper and copper alloys. For
new and retrofit installations, consideration should be given to using solid copper-base
alloys. Consideration should also be given to snap-on copper/copper alloy sheathings or
slipcovers for microbial protection.
Water fountains in hallways are available in vinyl-clad steel or stainless steel construction.
The faucets, spout, and activation device however, should be constructed with
antimicrobial copper alloys.
Stainless steel is the primary material for all types of operating room and other hospital
equipment. Products include operating tables, equipment stands, stools, poles, carts and
trays. These stainless steel items are receptive to disinfection, sterilization and sanitization,
which is important in the control of bacterial growth and transmission. However, nothing
can prevent recontamination of these surfaces after they have been cleaned. Consideration
of the antibacterial qualities of copper-based materials for these products should find
appeal and be widely accepted.
The healthcare environment offers numerous possibilities for antimicrobial touch surfaces.
Lists of common medical supplies and housekeeping touch surfaces that would benefit
from copper‘s hygienic properties are presented in Table 18.1 (medical supplies) and
Table 18.2 (housekeeping touch surfaces). A list of targeted surfaces identified by
physicians for the DoD hospital clinical trials was provided in Table 17.1.
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Table 18.1 — Potential Uses of Copper Alloys for Medical Equipment
Instrument handles
Equipment carts
Intravenous (IV) poles
Trays
Pans
Walkers
Stretcher plates
Computer keyboards
Exercise and rehabilitation equipment
Table 18.2 — Potential Uses of Copper Alloys for Housekeeping Touch Surfaces
Bedrails, handrails, stair rails
Push plates, kick plates and mop plates
Sinks, spigots and drains
Faucets
Soap dispensers
Handles and doorknobs
Grab bars in bathrooms
Panic bars on emergency room doors
Towel bars
Showerheads
Countertops and tabletops
Remote controls, call buttons and equipment controls
Bed trays
Locks, latches and trim
Door stops, door, drawer and cabinet pulls and protector guards
Toilet and urinal hardware
Closures
Vertical locking arms
Vertical cover guards
Protection bars
Light switches
Visitor chairs
Thermostat covers
Telephone handsets and surfaces
Kitchen surfaces (non-food contact)
Floors
Walls
Some copper hardware components in Table 18.1 and Table 18.2 are already being
manufactured for high-end commercial buildings. These items are almost always ordered
for aesthetic purposes, not for their antimicrobial benefits. Others, as mentioned in
Chapter XVII, are being manufactured as part of the DoD‘s clinical trials.
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Which copper alloy compositions are amenable for which hospital products? Michels
(2005) suggests the following:
- Uncoated copper should be substituted for stainless steel and aluminum in door
handles, push plates, faucets, grab bars, hand rails, stair rails, ventilation grilles, etc.
- Uncoated brass and bronze should be used for hardware retrofits. Due to their
functionality and decorative features, many banks, hotels, and high-end office
buildings already use these alloys in certain hardware products (e.g., revolving
doors, push plates, door handles, knobs, levers, push bars, hinges, locksets) to
convey elegance, quality, and status.
- Where resistance to the color of copper, brass, or bronze is an important or
perceived issue, the visual appeal of a silver-colored copper alloy, nickel silver
(comprised of copper, nickel, and zinc) and the variety of colors in other copper
alloys, may reduce consumer resistance.
Hospital Sanitizers and Disinfectants Do Not Affect the Performance of Copper Alloys
There are several categories of disinfectants and sanitizers used in healthcare facilities.
Most of them fit into the following categories:
- Chlorine-based
- Quaternary ammonia-based (Quat)
- Alcohol-based
- Phenol-based
- Other (e.g., citric acid as active ingredient)
The effect of these types of disinfection products has been assessed by the U.S. Copper
Development Association and others. When used according to manufacturer‘s instructions,
none of the disinfectants adversely affect copper alloy surfaces. Citric-acid based
disinfectants provide the added advantage of removing light staining and tarnish from
copper alloy surfaces.
Future Studies of Copper Alloy Surfaces as Antimicrobial Agents
Although much research has been conducted on the efficacy of copper alloys to kill a wide
range of microbes, more research is needed on different alloys, different pathogens, and in
different environmental conditions. The copper industry is in the process of obtaining a full
understanding of the potential market opportunities for its antimicrobial alloys.
Alternatively, hospital administrators should obtain a full understanding of potential
antimicrobial copper products that can help them reduce hospital-acquired infections at
their facilities.
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Creating Awareness Amongst Stakeholders
There is much interest in and awareness of contamination by microbial pathogens within
health-related facilities. However, since some of the most important advances in
antimicrobial touch surface research have been conducted in just the past few years,
information about the potential benefits of antimicrobial copper alloys has yet to be
effectively disseminated to stakeholders in the healthcare industry.
Healthcare organizations are attempting to provide guidelines for the control of
transmittable diseases. Unfortunately for all stakeholders, these guidelines do not
adequately address how to mitigate the colonization and growth of bacteria on surfaces.
The CDC, in conjunction with the U.S. Food and Drug Administration (FDA) and the
National Institutes of Health (NIH), chaired an interagency task force to design a public
health action plan to combat antimicrobial resistant strains of bacteria (see Interagency
Task Force in Chapter XXIII). This task force addressed the need to conduct further
research on antimicrobial resistance, potential impacts on humans and animals, clinical
research of useful products, and novel approaches in detecting, preventing and treating
antimicrobial-resistant infections. The task force, however, did not address
proactive/preventive measures to reduce the transfer of bacterial pathogens through
contact.
It is important to inform authorities at the CDC, FDA, and NIH about the strong potential
benefits of antimicrobial copper materials in health-related facilities.
The Infectious Disease Society (www.idsociety.org) suggests that a ―multipronged‖
approach be taken to combat MRSA. This includes antibiotic development initiatives,
antibiotic resistance research and preventive measures (e.g., hand hygiene, private room
placements, patient surveillance, contact precautions, etc.). Contact precautions suggested
by the Infectious Disease Society focus on protective clothing and equipment cleaning.
They do not, however, mention antimicrobial materials. Therefore, the Society should be
informed about the contribution that can be made by copper materials.
Having noted in both Chapter IV and this chapter that good hygiene policies are often not
satisfactorily implemented in healthcare facilities, opportunities abound to address
supplemental, preventive approaches against environmental contamination using copper-
based antimicrobial materials.
All health-related stakeholders, from doctors and hospital administrators to health agencies
and equipment manufacturers, should be made aware that copper alloys and formulations
have the efficacy to kill pathogenic microbes commonly found in health-related facilities.
They should also be made aware that infections from contaminated surfaces will probably
be reduced by replacing stainless steel, aluminum, and plastic touch surfaces of medical
supplies and medical housekeeping products with copper materials, wherever appropriate.
110
Follow-up studies, clinical trials, and case studies should continue to be conducted to
further evaluate and confirm the efficacy of antimicrobial copper materials and coatings in
health-related environments. Positive results from the EPA registration studies discussed in
Chapter XVI and the DoD clinical trials discussed in Chapter XVII will undoubtedly go
a long way toward making stakeholders aware of the antimicrobial value of copper touch
surfaces in healthcare environments.
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XIX
Conclusions
This compilation of information, data and research demonstrates that current hygienic
practices in healthcare facilities must be supplemented to protect public health. Infections
due to cross-contamination at hospitals and long-term care facilities continue to put the
public at risk for disease and death.
This paper presented a strong hygienic-based case for the value of copper and copper alloys
to help control bacterial load on environmental surfaces, including E. coli O157: H7, the
difficult-to-treat Methicillin-resistant Staphylococcus aureus (MRSA), and other microbes.
This case is based on copper‘s intrinsic ability to kill 99.9% of dangerous bacteria within
two hours.
Copper alloys are intrinsically antimicrobial. They provide a lifetime of efficacy. They do
not wear off and they cannot be scraped off.
No other materials can claim copper‘s effectiveness and long lasting capabilities: not
stainless steel, not plastic laminates, and not ―antimicrobial‖ coatings or adhesives made
with silver or organic disinfectants.
The market for products made with copper alloys is expected to materialize quickly
following EPA registration for the use and promotion of antimicrobial copper as a public
health benefit (Chapter XVI). This is due to strong, positive test results.
The market for products made with copper alloys is also expected to be bolstered should
DoD-funded clinical trials (Chapter XVII) prove the benefits of copper alloy touch
surfaces in hospital settings.
Clearly, there are challenges, as well as opportunities, for health authorities, equipment
manufacturers, regulators, and other stakeholders to take the next steps.
Hospitals are expected to become increasingly motivated to seek effective new solutions as
they become more responsible for costs of certain avoidable hospital-acquired infections in
patients. When Medicare stopped paying those charges in October 2008, insurance
companies were considering following suit. This is a real concern to hospitals and is
expected to encourage the entire healthcare industry to take all reasonable and effective
actions necessary to reduce infection rates.
The major hopeful solution presented in this paper is the replacement of stainless steel,
aluminum, plastic, with copper alloy surfaces. Copper alloys should be utilized in all
applications where their unique, intrinsic antimicrobial properties will help reduce
bacterial contamination that threatens human health.
112
As researchers and regulators obtain clinical understanding of the antimicrobial efficacy of
copper alloys, research will be expanded to integrate these benefits with important
attributes of copper alloys for specific applications, such as their formability, durability,
ease of fabrication, aesthetic appeal, surface finishes, corrosion resistance and tarnish
resistance.
Once copper alloys are clearly identified for specific hospital-related applications and made
available to the public, it is highly probable that antimicrobial copper touch surface
materials will be installed throughout new healthcare facilities, as well as retrofitted into
existing facilities in the US and around the world.
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XX
APPENDIX
Copper: Antimicrobial, Yet Also Essential for Humans,
Animals and Plants
While this paper highlights the health and commercial benefits of using copper to suppress
or inactivate unwanted microbial populations, it is important to emphasize that copper is, at
the same time, a micronutrient that is essential to all plant, animal, and human life.
This section provides a brief introduction about the importance of copper for good health.
Included are up-to-date discussions about the essentiality of dietary copper, recommended
daily intake of dietary copper, dietary copper deficiency and important food sources that
can prevent dietary copper deficiency.
Essentiality of Dietary Copper
Numerous studies have demonstrated to the worldwide medical community that copper is
necessary for the growth, development, and maintenance of bone, connective tissue, brain,
heart and many other body organs. Copper is involved in the formation of red blood cells,
the absorption and utilization of iron, and the synthesis and release of life-sustaining
proteins and enzymes. These enzymes produce cellular energy and regulate nerve
transmission, blood clotting and oxygen transport.
Copper is an essential cofactor for approximately a dozen cuproenzymes in mammals in
which copper is bound to specific amino acid residues in an active site (Prohaska and
Gabina, 2004). However, free cuprous ions react readily with hydrogen peroxide to yield
the deleterious hydroxyl radical. Therefore, copper homeostasis is regulated very tightly,
and unbound copper is extremely low in concentration.
Copper imported by the plasma membrane transport protein Ctr1 rapidly binds to
intracellular copper chaperone proteins. Atox1 delivers copper to the secretory pathway
and docks with either copper-transporting ATPase ATP7B in the liver or ATP7A in other
cells. ATP7B directs copper to plasma ceruloplasmin or to biliary excretion in concert with
a newly discovered chaperone, Murr1, the protein missing in canine copper toxicosis.
ATP7A directs copper within the trans-Golgi network to the proteins dopamine beta-
monooxygenase, peptidylglycine alpha-amidating monooxygenase, lysyl oxidase, and
tyrosinase, depending on the cell type.
CCS is the copper chaperone for the Cu/Zn-superoxide dismutase that protects cells against
reactive oxygen species; it delivers copper in the cytoplasm and intermitochondrial space.
Cox17 delivers copper to mitochondria to cytochrome c oxidase via the chaperones Cox11,
Sco1, and Sco2. Other copper chaperones may exist and might include metallothionein and
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amyloid precursor protein (APP). Genetic and nutritional studies have illustrated the
essential nature of these copper-binding proteins.
Copper is also known to stimulate the immune system, repair injured tissues, and promote
healing. More recently, copper has been attributed to helping neutralize "free radicals"
which can cause severe damage to cells.
Copper is essential for the normal growth and development of human fetuses, infants and
children. This was the conclusion of a review of a large body of published research
conducted at the Rowett Research Institute in Scotland and made available in a monograph
by the International Copper Association (McArdle and Ralph, 2001). According to the
authors, the human fetus accumulates copper from its mother during the third trimester of
pregnancy, apparently to ensure that it will have adequate supplies to carry out metabolic
functions after birth. Once born, a healthy infant will have four times the concentration of
copper as that of a full-grown adult. The copper will be stored in the liver and used to
satisfy the metabolic needs of the infant. Recent research has revealed that the very young
have special biochemical mechanisms for adequately managing copper in the body while
their life-long mechanisms develop and mature. (Obikoya 2008)
Metabolic Copper Deficiency
Few people are aware of the health disorders associated with dietary copper deficiency.
Yet, it is believed that at least 20 percent of the world‘s population suffers from these
maladies. Symptoms of copper deficiency include osteoporosis, osteoarthritis and
rheumatoid arthritis, cardiovascular disease, colon cancer and chronic conditions involving
bone, connective tissue, heart and blood vessels. Even a mild copper deficiency, which
affects a much larger percentage of the population, can impair health in subtle ways.
Symptoms of mild copper deficiency include lowered resistance to infections, reproductive
problems, general fatigue and impaired brain function.
Pregnant mothers who are severely deficient in copper could increase the risk of health
problems in their fetuses and infants. These problems include low birth weight, muscle
weakness and neurological problems.
In infants and children, copper deficiency may result in anemia, bone abnormalities,
impaired growth, weight gain, frequent infections (colds, flu, pneumonia), poor motor
coordination and low energy. To protect infants from copper deficiency, pregnant and
nursing women should, under a doctor's supervision, increase their dietary intake of copper.
(International Copper Association, 2007)
Nutritional Requirements
Because it is an essential metal, daily dietary requirements for copper have been
recommended by various national and international health agencies. For example, the
World Health Organization recommends a minimal acceptable intake of approximately 1.3
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mg/day. The recommended intake for healthy adult men and women in North America is
0.9 mg/day. Adequate copper intakes are estimated at 0.3 mg/day for children of 1–3 years,
0.4 mg/day for 4–8 years, 0.7 mg/day for 9–13 years, and 0.9 mg/day for 14–18 years.
These values are considered to be adequate and safe for the general population. (NAS,
2001)
Foods Containing Copper
Copper is an essential trace mineral that cannot be formed by the human body. It must be
ingested from foods. The best dietary sources of copper include seafood (especially
shellfish), organ meats (such as liver), whole grains, nuts, raisins, legumes (beans and
lentils) and chocolate. Other food sources that contain copper include cereals, potatoes,
peas, red meat, mushrooms, some dark green leafy vegetables (such as kale) and some
fruits (such as coconuts, papaya and apples). Tea, rice and chicken are relatively low in
copper but can provide a reasonable amount of copper when they are consumed in
significant amounts. Eating a balanced diet, with a range of food from different food
groups, is the best way to avoid copper deficiency.
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XXI
EPA Approved Master Label for Antimicrobial Copper Alloys Group I (April 2009)
ANTIMICROBIAL COPPER ALLOYS GROUP I+
+NOTE: Product labels will bear the name of a copper alloy specified in the
approved registration. Distributors may substitute a Product Brand Name in place of
the name of the copper alloy on the label.
Laboratory testing has shown that when cleaned regularly, this surface:
[Continuously reduces bacterial* contamination, achieving 99.9% reduction within two
hours of exposure.]
[Kills greater than 99.9% of Gram-negative and Gram-positive bacteria* within two hours
of exposure.]
[Delivers continuous and ongoing antibacterial* action, remaining effective in killing
greater than 99.9% of bacteria* within two hours.]
[Kills greater than 99.9% of bacteria* within two hours, and continues to kill 99% of
bacteria* even after repeated contamination.]
[Helps inhibit the buildup and growth of bacteria* within two hours of exposure between
routine cleaning and sanitizing steps.]
* Testing demonstrates effective antibacterial activity against Staphylococcus
aureus, Enterobacter aerogenes, Methicillin-Resistant Staphylococcus aureus
(MRSA), Escherichia coli O157:H7, and Pseudomonas aeruginosa.
The use of a Copper Alloy surface is a supplement to and not a substitute for standard
infection control practices; users must continue to follow all current infection control
practices, including those practices related to cleaning and disinfection of environmental
surfaces. The Copper Alloy surface material has been shown to reduce microbial
contamination, but it does not necessarily prevent cross contamination.
* * * * *
Active Ingredient:
Copper 96.2%
Other 3.8%
Total 100%
EPA Registration No. **** Made in the United States by *******
EPA Establishment No. ***** Distributed by *******
Net Contents: ******
117
DIRECTIONS FOR USE
It is a violation of Federal law to use this product in a manner inconsistent with its labeling.
[The directions in bracketed text below may be included in an insert. If so, there will be a
statement to see the insert for additional directions for use of the product.]
[Directions for Use in the insert also may include installation and operation instructions,
user manuals, and similar instructional materials appropriate for the end use product. No
additional pesticidal claims will be made as part of these materials.]
Proper Care and Use of Antimicrobial Copper Alloys: The use of Antimicrobial Copper
Alloys does not replace standard infection control procedures and good hygienic
practices. Antimicrobial Copper Alloys surfaces must be cleaned and sanitized
according to standard practice. Health care facilities must maintain the product in
accordance with infection control guidelines; users must continue to follow all current
infection control practices, including those practices related to disinfection of
environmental surfaces.
Copper Alloy surfaces may be subject to recontamination and the level of active bacteria at
any particular time will depend on the frequency and timing of recontamination and
cleanliness of the surface (among other factors). In order for the copper alloy surface to
have proper antimicrobial effect, the product must be cleaned and maintained according to
the directions included on this label.
This product must not be waxed, painted, lacquered, varnished, or otherwise coated.
Routine cleaning to remove dirt and filth is necessary for good sanitation and to assure the
effective antibacterial performance of the Antimicrobial Copper Alloy surface. Cleaning
agents typically used for traditional touching surfaces are permissible; the appropriate
cleaning agent depends on the type of soiling and the measure of sanitization required.
[Normal tarnishing or wear of Antimicrobial Copper Alloy surfaces will not impair the
antibacterial effectiveness of the product.]
This product can not be used for any direct food contact or food packaging uses.
[Antimicrobial Copper Alloys may be used in hospitals, other healthcare facilities, and
various public, commercial, and residential buildings for the non-food contact surfaces
listed below.] [The following statement will appear on the label if the use involves potential
exposure to outdoor conditions: Surfaces that may be exposed to outdoor environmental
conditions (e.g., handrails, shopping carts, child seats and ATM machines) are not
representative of indoor laboratory test conditions, and therefore, may impart reduced
efficacy if not cleaned when visibly soiled.]
Healthcare Facilities
o Bedrails, footboards
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o Over-bed tables
o Bed-side tables in hospitals, extended care facilities, senior housing etc.
(knobs, pulls, handles; surfaces)
o Handrails, (corridor/hallways) ( Senior housing), automatic door push
plates
o Stair rails, handrails, tubular railing, and supports, rail fittings T‘s, elbows
and brackets
o Bedrails, assistance rails,
o Toilet safety rails
o Carts
Hospital carts (table surfaces, handles, legs)
Computer carts
Record carts
Phlebotomy carts
Other Carts (tables/surfaces, shelving, railings, handles, pulls)
o Equipment carts (horizontal surfaces, frames, handles)
o Door push plates, kick plates, mop plates, stretcher plates
o Sinks: spigots, drains, sinks themselves
o Faucet: handles, spigot, drain control lever
o Water fountains: bubbler head, drain strainer, handle
o Alcohol sanitizer dispenser, handle
o Paper towel holders, facial tissue holders, toilet paper holders
o Air hand dryer, controls and push buttons on air hand dryers
o Hydrotherapy tanks (whirlpool tanks): shells, covers, headrests, drain
fittings (outer surfaces without water contact)
o Door handles, doorknobs (outer touch surfaces)
o Grab bars in bathrooms showers and bathtubs
o Panic bars on emergency room doors
o Towel bars
o Showerheads
o Countertops and tabletops (non-food use only)
o Hinges, locks, latches, and trim
o Door stops, door pulls, and protector guards
o Toilet and urinal hardware, levers, push buttons
o Toilet seat inlay for lifting of seat
o Closures
o Vertical locking arms
o Vertical cover guards
o Protection bars
o Light switches, switch plates
o Visitor chairs: armrests, metal frames
o Thermostat covers, control knobs and wheels
o Telephone handsets and surfaces (housings), keypad
o Kitchen surfaces (non-food contact only): table tops, counter tops, handles
(microwave, refrigerator, stove), cabinet doors, cabinet hinges, pulls,
backsplash, hoods, control knobs (appliances, fans)
119
o Floor tiles
o Ceiling tiles
o Wall decorative tiles
o Textiles (uniforms, curtains, sheets, pillow cases, etc.)
o Instrument handles
Medical equipment knobs, pulls and handles for:
Drug delivery systems
Monitoring systems
Hospital beds
Office equipment
Operating room equipment
Stands and fixtures
Types of knobs: e.g. Prong, fluted, knurled, push/pull, T-handle,
tapered, and ball knobs
o Intravenous (IV) poles, bases, hangers, clips
o Trays (instruments, non-food contact)
o Pans (bed)
o Walkers, wheelchair handles, and tubular components
o Computer keyboards: keys, housings, computer mouse surfaces
o Exercise and rehabilitation equipment, handles, bars
o Physical therapy equipment: physical therapy tables, treatment chairs and
portable taping tables
o Chairs (shower chairs, patient chairs, visitor chairs): rails, backs, legs, seats
o Lighting products: X-ray illuminators, operating rooms, patient
examination rooms, surgical suites, and reading lamps for hospital rooms
and assisted living facilities etc. Components can include bases, arms,
housings, handles, hinges)
o Headwall systems: the unit themselves, outlet covers, knobs and dials,
lighting units (lamp housings and adjustable arms), CRT monitors with
rotating knobs and levers and adjustments. Baskets, monitor housings,
knobs, baskets, tables, IV poles
o Critical care cart: Table top, drawer, drawer pull, lock, copper wire baskets
for storage of equipment and charts.
o Bedside lavatory: sink, faucet, handles, drawer pulls, toilet seat, toilet seat
cover, toilet handle, door and cabinet facings, counter tops
o Medical records: Chart holders, clipboards, filing systems
o Storage Shelving: wire shelving etc. for medical supplies
o Grab handles on privacy curtains
o Lids of laundry hampers, trash canisters, and other containers
o Closet rods and hangers
o Television controls: knobs, buttons, remote
o Monitor (television, computer, etc.) housing
o Soap holder
o Magazine rack
o Signage
o Coat rack and hooks
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o Shower curtain rings
o Radiator cover
o Bracelets
o Pens
o Badge clips
o Name tags
o Patient gown snaps
o Window sills, pulls and locks
o Electrical wallplates
Community Facilities (including various public and commercial buildings)
o Shopping cart handles, child seats, handrails
o Cash registers: housing, keypads
o ATM machines: keys, housing
o Gym/Health club lockers, locker handles, locker shelving, trainers‘ tables,
o Ice and water dispensers (outer surfaces without water contact)
o Elevator: handrail, control panel, buttons, interior walls, floor tiles, exterior
call button plate
o Paper towel dispensers. Housing itself, (turn) handle, (push) handle
o Soap holder
o Soap dispenser (wall mounted): push bar and dispenser itself
o Soap dispenser (sitting on counter): dispenser housing itself, push
mechanism
o Toilet paper dispenser (housing)
o Windows (crank), Locking mechanism, pull handles
o Window treatments (cord pulls), Venetian blinds (wands, cord pulls)
o Jalousie Windows (crank)
o Casement (cranks, levers, hinges)
o Single and double-hung windows (locks and pulls)
o Light switches, switch plates
o Lids of laundry hampers, trash canisters, and other containers
o Magazine rack
o Signage
o Coat rack and hooks
o Shower curtain rings
o Radiator cover
o Bracelets
o Badge clips
o Name tags
o Vending machines (non-food contact only)
o Window sills
o Electrical wallplates
o Clip boards
o Office supplies: paper clips, staplers, tape dispensers
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Residential Buildings (including homes, apartments, apartment buildings and
other residences
o Kitchen surfaces (non-food contact only): table tops, counter tops, handles
(microwave, refrigerator, stove), cabinet doors, cabinet hinges, pulls,
backsplash, hoods, control knobs (appliances, fans)
o Bedrails, footboards
o Handrails
o Stair rails
o Door push plates
o Sinks: spigots, drains, sinks themselves
o Faucet: handles, spigot, drain control lever
o Paper towel holders, facial tissue holders, toilet paper holders
o Door handles, doorknobs (outer touch surfaces)
o Grab bars in bathrooms showers and bathtubs
o Towel bars
o Showerheads
o Countertops and tabletops
o Hinges, locks, latches, and trim
o Door stops, door pulls, and protector guards
o Toilet and urinal hardware, levers, push buttons
o Toilet seat inlay for lifting of seat
o Light switches, switch plates
o Thermostat covers, control knobs and wheels
o Telephone handsets and surfaces (housings), keypad
o Floor tiles
o Ceiling tiles
o Wall decorative tiles
o Computer keyboards: keys, housings, computer mouse surfaces
o Exercise equipment, handles, bars
o Windows (crank), Locking mechanism, pull handles
o Window treatments (cord pulls), Venetian blinds (wands, cord pulls)
o Jalousie Windows (crank)
o Casement (cranks, levers, hinges)
o Single and double-hung windows (locks and pulls)
o Television control knobs and buttons
o Lids of laundry hampers, trash canisters, and other containers
o Closet rods and hangers
o Television remote
o Soap holder
o Magazine rack
o Coat rack and hooks
o Shower curtain rings
o Radiator cover
o Window sills
o Electrical wallplates
o Office supplies: paper clips, staplers, tape dispensers
122
o Monitor (television, computer, etc.) housing
Mass Transit Facilities o Handrails
o Stair rails, tubular railing, and supports; elbows and brackets
o Door push plates, kick plates
o Door handles, door knobs (outer touch surfaces)
o Grab bars and handles
o Tiles: wall, floor, ceiling (non-porous)
o Chairs and benches: rails, backs, legs, seats
o Window sills, pulls, and handles
o Signage
o Vending machines (non-food contact only)
Other o Playground equipment (outdoor): bars, handles, chains, push plates,
handrails, stair rails and risers, wheels, knobs, flooring
o Chapel pews
o Eye glass frames and protective eye wear
o Pens
o Combs
o Ashtrays
Outdoor uses are limited to those specified in the above list.
STORAGE AND DISPOSAL
ANTIMICROBIAL COPPER ALLOYS should be disposed in a responsible manner,
including recycling.
WARRANTY STATEMENT
If used as intended, ANTIMICROBIAL COPPER ALLOYS are wear-resistant and the
durable antibacterial* properties will remain effective for as long as the product remains in
place and is used as directed.
Note: With the exception of the product name and the percentage of active ingredient,
the EPA approved Master Labels for the six groups of registered alloys are identical.
123
XXII
EPA Registered Antimicrobial Copper Alloys
Please note that this list of registered alloys will continue to expand. For the most up to
date listing, please visit antimicrobialcopperalloys.org.
Antimicrobial Copper Alloys Group I (137 Alloys)
UNS No. Cu% UNS No. Cu% UNS No. Cu%
C10100 99.99 C14530 99.97 C19700 99.0
C11040 99.9 C14700 99.6 C19710 99.6
C11045 99.9 C15000 99.8 C19720 99.6
C10200 99.95 C15100 99.8 C19750 98.6
C10300 99.99 C15500 99.8 C19800 97.3
C10400 99.95 C15715 99.7 C19900 96.9
C10500 99.95 C15720 99.6 C40400 97.0
C10700 99.95 C15725 99.5 C40810 95.5
C10800 99.99 C15760 98.8 C40820 96.6
C10910 99.95 C15815 98.4 C40850 95.5
C10920 99.9 C16200 99.0 C50100 99.4
C10930 99.9 C16500 98.6 C50200 98.8
C10940 99.9 C17000 98.3 C50500 98.7
C11000 99.96 C17200 98.1 C50510 98.3
C11010 99.9 C17410 98.6 C50580 98.5
C11020 99.9 C17450 98.7 C50590 98.0
C11030 99.9 C17460 98.5 C50700 98.3
C11100 99.96 C17500 96.9 C50705 98.0
C11300 99.96 C17510 97.8 C50710 97.8
C11400 99.96 C17530 96.0 C50715 97.9
C11500 99.96 C18661 99.6 C50725 95.6
C11600 99.96 C18665 99.3 C50780 97.8
C11700 99.9 C18835 99.2 C50900 96.7
C12000 99.99 C18900 98.7 C51100 95.6
C12100 99.99 C18980 98.0 C51180 95.5
C12200 99.98 C19000 98.6 C51190 95.2
C12210 99.98 C19002 97.4 C64710 95.8
C12220 99.95 C19010 98.4 C64740 95.6
C12300 99.98 C19015 98.1 C64750 97.2
C12500 99.9 C19020 98.0 C64760 97.0
C12510 99.9 C19025 98.0 C64770 96.2
C12900 99.9 C19030 97.1 C64900 97.6
C13100 99.8 C19200 99.0 C65100 98.5
124
UNS No. Cu% UNS No. Cu% UNS No. Cu%
C14180 99.9 C19210 99.9 C65500 97.0
C14181 99.9 C19215 97.5 C65600 96.6
C14300 99.9 C19220 99.5 C70100 96.5
C14410 99.8 C19260 99.0 C70200 97.5
C14415 99.9 C19280 97.9 C70230 95.2
C14420 99.9 C19400 97.4 C70240 96.1
C14500 99.5 C19410 97.1 C70250 96.1
C14510 99.5 C19450 96.2 C70260 97.6
C14520 99.5 C19500 97.0 C70265 97.0
C70270 96.3 C70350 96.3 C81100 99.7
C70280 97.0 C70370 95.8 C81200 99.95
C70290 95.8 C80100 99.95 C82200 97.9
C70310 96.6 C80410 99.9
Antimicrobial Copper Alloys Group II (54 Alloys)
UNS No. Cu% UNS No. Cu%
C21000 95.0 C61000 92.0
C22000 90.0 C61300 90.3
C22600 87.5 C61400 91.0
C40500 95.0 C61500 90.0
C40860 94.8 C61550 92.0
C41000 92.0 C61800 89.0
C41120 90.5 C63800 95.0
C42000 89.5 C64730 94.6
C42200 87.5 C64780 94.5
C42220 89.5 C64785 88.1
C42500 88.5 C66200 88.8
C42520 89.8 C70400 92.4
C42600 88.5 C70500 93.2
C51000 94.8 C70600 88.6
C51080 94.5 C70610 87.3
C51800 94.8 C70620 88.0
C51900 93.8 C70690 90.0
C51980 93.5 C70700 90.0
C52100 92.0 C70800 88.5
C52180 91.8 C72500 88.2
C52400 90.0 C72650 87.5
C52480 89.6 C89320 89.0
C55180 95.0 C95200 87.7
C55181 92.8 C95210 87.8
C55280 91.0 C95300 89.0
C55281 89.0 C95600 90.3
C55282 88.3 C96200 88.6
125
Antimicrobial Copper Alloys Group III (48 Alloys)
UNS No. Cu% UNS No. Cu%
C23000 85.0 C66420 84.2
C23030 84.5 C66430 84.4
C23400 82.5 C69100 82.5
C24000 80.0 C71000 79.0
C43600 81.5 C72700 84.8
C55283 86.8 C72800 82.0
C55284 80.0 C89510 87.0
C55385 86.7 C89520 86.0
C61900 86.5 C89835 87.0
C62200 84.8 C90800 87.0
C62300 87.0 C95220 86.8
C62400 86.0 C95400 83.2
C62500 82.7 C95410 82.7
C62580 83.5 C95420 85.2
C62581 82.5 C95500 80.0
C62582 81.5 C95510 82.0
C63000 82.0 C95520 79.2
C63010 82.0 C95800 81.0
C63020 79.7 C95820 79.2
C63200 82.0 C95900 83.3
C63280 80.3 C96300 81.9
C66300 86.0 C96800 81.6
C66400 86.5 C96950 79.1
C66410 86.5 C96970 85.0
Antimicrobial Copper Alloys Group IV (29 Alloys)
UNS No. Cu% UNS No. Cu%
C25600 72.0 C69050 72.5
C26000 70.0 C69300 75.0
C26130 70.0 C71100 77.0
C26200 68.5 C71300 75.0
C44250 74.5 C71500 69.5
C44300 71.0 C71580 69.0
C44400 71.0 C71581 68.9
C44500 71.0 C71590 70.0
C55285 76.0 C72900 77.0
C63380 74.6 C72950 73.9
C66700 70.0 C95700 73.2
C66950 69.8 C95710 74.5
C68700 77.5 C96400 68.2
C68800 73.5 C96900 76.8
126
UNS No. Cu% UNS No. Cu%
C99300 71.3
Antimicrobial Copper Alloys Group V (8 Alloys)
UNS No. Cu% UNS No. Cu%
C71520 67.7 C75700 65.0
C71640 65.0 C89940 66.0
C71700 67.8 C96600 67.4
C75200 65.0 C96700 67.1
Antimicrobial Copper Alloys Group VI (6 alloys)
UNS No. Cu% UNS No. Cu%
C27200 63.5 C66900 63.5
C28000 60.0 C74400 64.0
C49300 60.0 C76400 60.0
127
XXIII
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