PhD in BioMedical Engineering (Ohio St.), Masters in Electrical Engineering (Ohio St.), J.D. (Concord Law School)

Senior management positions with Pfizer, Baxter, American Hospital Supply

Author of more than 100 peer-reviewed papers, holds more than 50 patents

Reviewer for National Institute of Health

Dr. Colette Cozean

Failures of Current Hand Hygiene, and the Search for

SolutionsColette Cozean, PhD

Promise of Alcohol Sanitizers Failure of Alcohol Sanitizers Reasons for Failure The Ideal Product Potential Solutions

Summary

Alcohol Sanitizer showed more complete kill against bacteria than soap and water

Alcohol is much more convenient, with the potential to decrease time spent while increasing compliance

Promise of Alcohol Sanitizers

After more than 10 years of alcohol sanitizer use, 5% of patients get an HAI, 90,000 deaths

Studies – 7 comparison studies between handwashing and alcohol sanitizer in medical◦ 4 Studies show alcohol increases infections◦ 2 Studies report improvement in HAIs with alcohol◦ 1 Study shows no difference in surgical site

infections

Results of Alcohol Sanitizers

Fendler et al, The Impact of hand sanitizer use on infection rates in an extended care facility, AJIC, 30:4, 226-33, 2002Hilburn et al, Use of alcohol hand sanitizer as an infection control strategy in an acute care facility, AJIC, 31:2, 109-116, 2003Rupp M et al, Prospective, Controlled, Cross‐Over Trial of Alcohol‐Based Hand Gel in Critical Care Units, Infection Control and Hospital Epidemiology; 29:1, 2008Larsen E et al, Effect of Antiseptic Handwashing vs Alcohol Sanitizer on Health Care–Associated Infections in Neonatal Intensive Care Units, Arch Pediatr Adolesc Med. 2005;159(4):377-383

Is it blinded? Is it randomized? Is it a crossover design? Are there any potential confounding

factors? Is it large enough to be statistically

significant? Who sponsored the study?

Evaluating Clinical Trials

3 ICUs, crossover (multiple) study, 3,000+ pts, compared CHG handwash vs. alcohol sanitizer, sponsored by Calgon-Vestal

Shown significant increase in HAIs with alcohol

University of Iowa Study

Change with AlcoholOverall +33.4%

UTI +40.0%Skin

Infections+93.0%

GI Infections +436%Doebbeling BN, Stanley GL, Sheetz CT, et al. Comparative efficacy of alternative handwashing agents in reducing nosocomial infections in intensive care units, New England Journal of Medicine, 1992; 327: 88-93

Nearly 3,000 pts, 2 NICUs, crossover, comparison with 2% CHG handwash

Increase in HAIs of 27.3% overall, and in 4/5 categories, sponsored by 3M (Avagard)

New York Presbyterian Hospital Study

Change with AlcoholOverall +27.3%

Bloodstream +23.0%Pneumonia +29.4%

Skin Infections

+77.4%

CNS +6.0%Conjunctivitis -15.8%Larsen E et al, Effect of Antiseptic Handwashing vs Alcohol

Sanitizer on Health Care–Associated Infections in Neonatal Intensive Care Units, Arch Pediatr Adolesc Med. 2005;159(4):377-383

Two-year study, 2 ICUs, crossover, monitored compliance and HAIs, sponsored by GOJO, compared against PCMX soap

No improvement noted with addition of alcohol sanitizer

Worse than baseline in 4/6 categories, equivalent in 1/6, improvement in 1/6.

University of Nebraska

Rupp M et al, Prospective, Controlled, Cross‐Over Trial of Alcohol‐Based Hand Gel in Critical Care Units, Infection Control and Hospital Epidemiology; 29:1, 2008

Study in 6 surgical centers, randomized, crossover (multiple) 4,000+ pts

Compared alcohol vs. CHG or iodine as a surgical scrub in between patients, when hands were not visibly soiled

No difference between handwashing and alcohol rub (2.48% vs. 2.44%), concluded alcohol was equivalent.

Sponsored by Rivardis Laboratories

Surgical Site Infection Study

Parienti JJ et al, Hand-rubbing with an aqueous alcoholic solution vs. traditional surgical hand-scrubbing and 30-day surgical site infection rates: a randomized equivalence study, JAMA, 2002; 288:722-727

Showed a 30% decrease, sponsored by GOJO Compared against a PCMX soap, not CHG or

other top-tier antimicrobial No crossover design Significant differences between control and

experimental groups◦ Exp. group only in residential wards◦ Control group on main floor, with cafeteria, dialysis,

recreation/activity area, and rehab room – all common areas where germs can be transmitted

◦ Control group (1:8.5 staff/pt), Exp. group (1:4.5)

Extended Care Facility Study

Fendler et al, The impact of alcohol hand sanitizer use on infection rates in an extended care facility, AJIC, 30:4, 226-233, 2002

Showed 36% decrease, sponsored by GOJO Also compared against PCMX soap No crossover design Gave additional education to staff, including

in-service, posters, brochures, and reminders, that were not given to controls

Gave patients individual bottles of hand sanitizer and additional education

Only performed in orthopedic surgery suite, not in general ward (SS infections and UTIs)

Ortho Surgery Study

Hillburn et al, Use of alcohol hand sanitizer as an infection control strategy in an acute care facility, AJIC, 31:2, 109-166, 2003

Randomized/Crossover

Confounding Factors

Valid Comparison Product

Sponsor Result

Doebbeling Yes No Yes Calgon-Vestal

Increase of 33%

Larsen Yes No Yes Avagard Increase of 27%

Parienti Yes No Yes Rivardis No difference

Rupp Yes No No GOJO Slight increase

Fendler No Yes No GOJO Decrease of 30%

Hillburn No Yes No GOJO Decrease of 36%

Improves compliance and skin condition No improvement in HAIs Never shown in a crossover study to offer

improvement Never shown in any trial to be better than top-

tier antiseptic handwashes (CHG, iodine, etc.), only PCMX◦ “PCMX had the weakest immediate and residual

activity of any of the agents studied…studies (2) demonstrated the immediate and residual activity of PCMX was inferior to both CHG and povidone-iodine.” – CDC Hand Hygiene Guidelines, 2002

Results in Hospitals

Study of 61 long-term care facilities, sponsored by the CDC, largest multi-center look at medical infections ever done.

Showed that facilities that rely on alcohol sanitizers were six times more likely to have an illness outbreak (Norovirus) than ones relying on soap and water alone.

Only study unfunded by sanitizer company, and truly “real-world” situation

Other Medical Trials

Blaney D et al, Use of alcohol-based hand sanitizers as a risk factor for norovirus outbreaks in long-term care facilities in northern New England: December 2006 to March 2007, American Journal of Infection Control, 39 (4) 296-301, 2011CDC, Vessel Sanitation Program, http://www.cdc.gov/nceh/vsp/surv/gilist.htm

Alcohol sanitizers kill bacteria faster and more completely than soap and water. They are more convenient and more widely used.

Why have we not seen the anticipated drop in infection and illness?

Reasons for Failure

“Antiseptic handwash….[should be] broad-spectrum, fast-acting, and if possible

persistent.” CDC Guidelines, 2002

“Persistence, defined as prolonged activity, is a valuable attribute that assures antimicrobial

activity during the interval between washings, and is important to a safe and effective

healthcare personnel handwash”FDA Tentative Final Monograph, 1994

Persistence

“Alcohols are rapidly germicidal when applied to the skin, but they have no appreciable

persistent (i.e., residual) activity.”CDC Hand Hygiene Guidelines, 2002

Kills the bacteria on the skin, but hands can immediately become recontaminated by the next surface or patient touched.

Compliance has to be perfect in order to eliminate risk of transmission

1. Lack of Persistence

Determine if preparations with persistent antimicrobial activity reduce infection rates

more effectively than do preparations whose activity is limited to immediate effectCDC Hand Hygiene Guidelines, 2002,

“Hand Hygiene Research Agenda”

CDC Hand Hygiene Research Agenda

Because HCWs <health care workers> may wash their hands….as many as 30 times per shift, the tendency of products to cause skin irritation and dryness is a substantial

factor that influences acceptance, and ultimate usage

CDC Hand Hygiene Guidelines, 2002

2. Lack of Compliance

Studies show that healthcare workers only comply with hand hygiene protocols 40-50% of the time

CDC studies have shown that 25% of HCWs have contact dermatitis from their hand hygiene products. Other studies put this number closer to 50%. Overall, 85% of HCWs have reported skin problems

Without persistence, each failure leaves the patient and worker open to pathogen transmission.

2. Lack of Compliance

Erasmus V et al. Systematic Review of Studies on Compliance with Hand Hygiene Guidelines in Hospital Care, Infection Control and Hospital Epidemiology, 31(3) 2010CDC Guidelines for Hand Hygiene, 2002

Approximately 22% of HAIs are viral, though we typically think of them as bacterial

Alcohol sanitizers are relatively ineffective against non-enveloped viruses

3. Lack of efficacy against viruses

Researchers at Emory University showed that rinsing the hands with water alone was more effective than using an alcohol sanitizer against Norovirus

3. Lack of efficacy against viruses

Lack of Persistence◦ Every failure to use product leaves HCW exposed

Lack of Compliance◦ Drying effects of alcohol cause skin irritation,

reducing usage and compliance Lack of Efficacy against Viruses

◦ Viruses cause 22% of HAIs, and a high percentage of visitor illnesses (flu, colds, stomach flu, etc.). Alcohol sanitizers less effective than water rinse against many non-enveloped viruses

Failures of Alcohol Sanitizers

The Ideal SanitizerIdeal

SanitizerAlcohol

SanitizerFast-acting

Effective against bacteria

Effective against viruses Less effective than water rinse

Persistent No persistence

Non-irritating (compliance) 40-50% compliance. 25-50% of HCWs report contact dermatitis

Non-alcohol sanitizers

Alcohol-plus sanitizers

Other Alternatives

“Immediate efficacy occurs more slowly than that of alcohols” – CDC Guidelines

“It has in-vivo efficacy against enveloped viruses…but substantially less activity against non-enveloped viruses” - CDC

High skin irritation Some persistence

CHG

  HibiClens (4% CHG)*

Acinetobacter baumannii 1 minBacteroides fragilis 10 minutesEnterococcus faecalis 10 minutesEnterococcus faecium 10 minutesStaphylococcus aureus 10 minutesStaphylococcus epidermis 3 minStaphylococcus saprophyticus

3 min

Streptococcus pyogenes 10 minutes

Serious health concerns, lawsuits against FDA and Dial, unable to pass the new FDA regulations governing soaps

Slower immediate activity than alcohol Relatively ineffective against gram-negative

bacteria, even resulting in contamination High skin irritation Persistent

Triclosan

Slow-killing (2+ minutes) Relatively weak against gram-negative

bacteria Good antiviral activity Persistent Well-tolerated on the skin

QATs

BZT (0.2%)

Iodine (7.5%)

CHG (0.75%)

PCMX (1.0%

)

CHG (4.0%)

Triclosan (0.3%)

-25

-20

-15

-10

-5

0

5

10

Dermal Moisture after 100 Uses

Day 1 Day 2 Day 3 Day 4 Day 5

Skin Irritation

BZT (0.2%) CHG (0.75%) PCMX (1.0%) Triclosan (0.3%) CHG (4.0%)0

1 1 1

3.5

Skin Irritation after 5 Day Dermal Test

Non-alcohol sanitizersIdeal Alcohol CHG Triclosa

nQATs

Fast-actingBacteriaVirusesPersistenceNon-irritating

Use a combination of alcohol (immediate kill) and another antimicrobial (persistence)

Avagard (61% ethanol, 1% CHG), ChloraPrep (70% isopropyl alcohol, 2% CHG)

Surgicept (70% alcohol, BZK, CHG) Typically used only as surgical scrubs,

increase skin irritation (alcohol + additional irritating ingredient)

Alcohol-Plus Products

Overall Comparison

Ideal Alcohol Non-alcohol

Alcohol + (CHG, QAT)

Fast-actingBacteriaVirusesPersistenceNon-irritating

CDC Recommendations“Selection committees must consider factors that can affect the overall efficacy of such products, including the relative efficacy of antiseptic agents against various pathogens and acceptance of hand hygiene products by personnel. Because HCWs may wash their hands….as many as 30 times per shift, the tendency of products to cause skin irritation and dryness is a substantial factor that influences acceptance, and ultimate usage”

“An antiseptic…(should be) broad-spectrum, fast-acting, and if possible, persistent.”