Dallas, TX November 2–4, 2012 Alternate Lock Solutions in Patients Receiving Parenteral Nutrition Deborah Andris MSN APNP Division of Colorectal Surgery

Dallas, TX • November 2–4, 2012

Alternate Lock Solutions in

Patients Receiving Parenteral Nutrition

Deborah Andris MSN APNP

Division of Colorectal Surgery

Medical College of Wisconsin


Objectives

• Discuss alternate catheter lock solutions for central venous access devices

• List potential usefulness in patients receiving long-term PN


Parenteral Nutrition (PN)

• Nutrition given directly into bloodstream via CVC

• Bypasses normal digestion in the gut

• Complete nutritional needs met

• Can be short or long term

• Goal of Home PN– Maintain nutritional status; minimize

complications


Impact of CLABSI in Home PN Patient

• Most common infectious complication

• Compounded in patients with limited access sites

• Contributes to increased healthcare costs– $33,000 to $65,000 per episode– $2.3 billion annually in U.S.

• Estimated attributable mortality 12-35% per infection

Pitet D, JAMA 1994;271:1598Orsi GB, Infect Control Hosp Epidemiol 2002;23:190



• Increased Risk for CLABSI– pH and nutritional components– Dextrose supports bacterial growth– Fat emulsion supports growth of fungi– S. epidermidis most common organism

• Typical presentation

Beraud G, Eur J Clin Microbiol Infect Dis May 2012; Epub



• Frequent hospitalizations– Increased LOS

• Loss of work/family time

• Interruption of nutrition support

• Loss of access

• Depression

• Increased risk for septic complications, chronic thrombosis, and antibiotic resistance




Intraluminal Colonization and Biofilms

“Bacteria prefer a community based, surface bound, sedentary lifestyle to a nomadic existence”

W. Michael Dunne

• Costerton, 1978– First theory of biofilm adhesion


Biofilms Defined

• Sessile microbial community

• Organisms produce an extracellular polymeric substance (matrix)

• Forms within 3 days of catheter insertion

• Intraluminal biofilm formation predominates after 30 days

Donlan RM, CID 2011;52:1038



Influences on Biofilm Formation

• Catheter material

• Presence of conditioning film

• Hydrodynamics

• Physical/chemical properties of liquid in contact with device

• Properties of microbial cell surface



Organisms Commonly Associated with Biofilms• Candida albicans• Coagulase-negative staphylococci• Enterococcus spp.• Klebsiella pneumoniae• Pseudomonas aeruginosa• Staphylococcus aureus


AntibioticsAntibiotics

AntibodiesAntibodies

Glycocalyx EnclosedGlycocalyx EnclosedMicrocolonyMicrocolony

PROTECTIONPROTECTION

NUTRIENT TRAPPINGNUTRIENT TRAPPING

ADHERENCEADHERENCE

Catheter SurfaceCatheter Surface

PhagocytesPhagocytes


“Established” Biofilm• Patient symptoms elicited when

aggregates of cells, endotoxins or other pyrogenic substances are dispersed

• Extracellular polymeric substance matrix prevents perfusion of antimicrobial

• Organisms are dormant

• Biofilm environment adversely affects antimicrobial activity


SEM of S. epidermidis on intraluminal surface of SEM of S. epidermidis on intraluminal surface of Hickman catheterHickman catheter


TEM of S. epidermidis on intraluminal surface of Hickman TEM of S. epidermidis on intraluminal surface of Hickman cathetercatheter


Historical Perspective

• 1988 Messing reported use of ABL in home PN patients

• Initial studies/use focused on antibiotics

• Chelating agents and ethanol followed

• 1988-1994 - 6 papers

1994-2003 – 35 papers

2003-2012 – 122 papers


Rationale for Use of Antibiotic Lock

• Catheter is colonized intraluminally

• Allows for adequate drug to be delivered to site of colonization

• Goal of therapy– Sterilize catheter lumen– Eliminate biofilm

Messing B, JPEN 1988;12:185


“Lock” Therapy Defined

• Antimicrobial or antiseptic solution instilled into the CVAD

• Dwells intraluminally; various times

• Commonly used antibiotics

• Prevention– High risk patient populations

• Treatment


Current Use of ABL

• Recent literature review

• ABL effective– High concentration of antibiotic– Dwell times > 12 h– Duration of 14 days of treatment

• Optimal concentration and duration unknown



ABL Risks

• Antibiotic resistance

• Stability of antimicrobials

• Expense

• Availability


Lock Therapy

• CDC guidelines do not recommend use of prophylactic antibiotic lock except in patients with history of multiple CR-BSI

• Ethanol as a locking agent is not approved by the FDA or the IDSA


Novel Catheter Lock Strategies

• Avoid use of antimicrobial agents

• May combine with antimicrobials

• Potential Applications:– Eliminate biofilm formation on indwelling

catheters– Prevent re-growth of organisms on device– Resolve patient symptoms


Novel Catheter Lock Strategies

• Chelating Agents– Disodium or Tetrasodium EDTA– Sodium Citrate

• Ethanol

• Biofilm Dispersants

• Bacteriophage



Chelating Agents• Metal cations maintain the biofilm matrix

• Validated in human studies

• Action– Antimicrobial effects

• Chelates metal ions essential for structural integrity of gram negative organisms

• Releases endogenous phospholipases• Mechanism against gram positive organisms

unknown

– Destabilizes biofilm structureDonlan RM, CID 2011;52:1038


Chelating Agents

• Potential Application– Lock to remove established biofilm,

bacteria, and fungi– Used in combination with antimicrobial

agents– 40 mg/mL concentration– Tetrasodium EDTA may have improved

spectrum of activity– Resistance does not develop over time


Research

• Raad, 1997– EDTA with minocycline showed to impact on the prevention of CLABSI in

patients with recurrent infections– Suggested EDTA alone may be effective

• Kite, 2004– Demonstrated efficacy of tetrasodium EDTA to eradicate biofilm from

hemodialysis catheters in vivo

• Percival, 2005– In vitro model demonstrating tetrasodium EDTA could eradicate biofilms

• Brookstaver, 2009 – In vitro model demonstrated significant reduction of biofilms from

staphylococcus spp and P. aeruginosa in hickman catheter segments with disodium EDTA in combination with a variety of antibiotics

Raad I, CID 1997;25:149

Kite P, J Clin Microbiol 2004;42:3073

Percival S, Inf Control and Hosp Epidemiol 2005;26:515

Bookstaver PB, Annals of Pharmacotherapy 2009;43:210


Ethanol Lock

• Validated in human studies

• Action – Antimicrobial – Penetrates the extracellular polymeric

substance – Denatures protein



Ethanol Lock

• Potential Application– Lock treatment to remove established biofilm and

bacteria– Emerged as preventive strategy

• Benefits over ABL– No concern for resistance– Bacteriacidal/fungicidal properties– Not dependent on sensitivity to antimicrobials– Inexpensive– Increased value in multi-drug resistant organisms


Ethanol Lock Technique

• 3 mL 70% ethanol solution; compounded in pharmacy and placed in pre-filled syringe

• Begin use immediately after CVC placed• Administer after cycled PN and allow to dwell

maximum time patient disconnected from infusion

• Use only in silicone catheters• Flush line with NS• Incompatible with heparin or citrated liquids

Maiefski M, Inf Control and Hosp Epidem 2009;30:1096


Research - Safety

• Crinch, 2005– Studied mechanical properties of

polyurethane and silicone catheters in vitro– Exposed catheters to 70% ethanol for 10

weeks– Negligible impact on integrity – Results suggest use of ethanol lock safe in

both catheter typesCrinch CJ, Infect Control Hosp Epidemiol 2005;26:708


Research - Stability

• Cober, 2007

• Studied stability of 70% ethanol in syringes

• Concluded solution stable for 14 days

• According to USP Chapter 797 guidelines - stable for 9 days

Cober MP, Am J Health Syst Pharm 2007;64:2480


Clinical Research

• Opilla, 2007

• Retrospective review

• 9 adult home PN patients with history of recurrent infection

• 70% ethanol; 2-4 hour dwell time

• Demonstrated decrease in infection rate from 8.3/1000 days to 0.3/1000 days with use of prophylactic lock

Opilla MT, JPEN 2007;31:302


Clinical Research

• John, 2012• Retrospective review• 31 adult home PN patients with history of recurrent infection; all

on prophylactic locks• PICC’s and Tunneled catheters• Outcomes were compared pre and post ethanol lock with each

patient serving as their own control• 70% ethanol; dwell times varied• Results:

– 273 CLABSI related admissions pre ethanol lock vs 47 post ethanol lock– Decrease in positive quantitative cultures from 96 pre-lock to 12 post-lock– Reduction in need for catheter change

Bijo J, JPEN 2012;36:603


Biofilm Dispersants

• Not validated in human studies

• Action: disperses cells from the biofilm surface

• Potential Application– Lock to remove established biofilm,

bacteria, and fungi– Used in combination with antimicrobial

agents


Bacteriophage

• Used in the 1920’s and 1930’s to treat bacterial infections

• Not validated in human studies• Action:

– Virus infects bacteria and injects it’s genetic material

– Antibacterial properties– Degrades the EPS


Bacteriophage

• Potential Application– Decrease bacterial attachment– Kill biofilm associated cells– Eradicate the biofilm matrix

• Pretreatment of the catheter

• Lock therapy

Dallas, TX • November 2–4, 2012Electron micrograph of Bacteriophages


The Future• Nitric Oxide

– Releases NO from coated catheter surface– Augments immune system

• GlmU Enzyme Inhibitor– Antimicrobial; anti-adhesin– Pre-treat catheter to prevent adhesion

• RIP Quorum-Sensing Inhibitor– Inhibits quorum sensing needed for S.

aureus biofilm formation– Injection


Application to the Infusion Therapy

Nurse• Understanding of the impact of biofilms on treatment

of CLABSI will help practitioners to plan and evaluate their care

• Elimination of biofilms remains a challenge• Important to have increased awareness of alternative

approaches for the treatment/prevention of CLABSI that avoid use of antibiotics

• New therapy goals: – eliminate biofilm – prevent regrowth of organisms– resolve patient symptoms


Application to the Infusion Therapy Nurse

Research Opportunities

• Questions related to technique– Optimal concentration– Dwell times– “To flush or not to flush”

• Cost savings analysis

• Impact on QOL in Home PN patients


Documents

Dallas, TX November 2–4, 2012 Alternate Lock Solutions in Patients Receiving Parenteral Nutrition Deborah Andris MSN APNP Division of Colorectal Surgery