Transcript Presentation Title

Alternate Lock
Solutions in Patients
Receiving Parenteral
Nutrition
Deborah Andris MSN APNP
Division of Colorectal Surgery
Medical College of Wisconsin
Dallas, TX • November 2–4, 2012
Objectives
• Discuss alternate catheter lock solutions
for central venous access devices
• List potential usefulness in patients
receiving long-term PN
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
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;271:1598
Orsi GB, Infect Control Hosp Epidemiol 2002;23:190
Dallas, TX • November 2–4, 2012
Impact of CLABSI in Home PN Patient
• 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
Dallas, TX • November 2–4, 2012
Impact of CLABSI in Home PN Patient
• Frequent hospitalizations
– Increased LOS
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Loss of work/family time
Interruption of nutrition support
Loss of access
Depression
Increased risk for septic complications,
chronic thrombosis, and antibiotic
resistance
Dallas, TX • November 2–4, 2012
Dallas, TX • November 2–4, 2012
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
Intraluminal Colonization and Biofilms
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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
Dallas, TX • November 2–4, 2012
Intraluminal Colonization and Biofilms
Organisms Commonly Associated with Biofilms
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Candida albicans
Coagulase-negative staphylococci
Enterococcus spp.
Klebsiella pneumoniae
Pseudomonas aeruginosa
Staphylococcus aureus
Dallas, TX • November 2–4, 2012
Antibiotics
Antibodies
Phagocytes
PROTECTION
Glycocalyx Enclosed
Microcolony
ADHERENCE
Catheter Surface
NUTRIENT TRAPPING
Dallas, TX • November 2–4, 2012
“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
Dallas, TX • November 2–4, 2012
SEM of S. epidermidis on intraluminal surface of
Hickman catheter
Dallas, TX • November 2–4, 2012
TEM of S. epidermidis on intraluminal surface of Hickman
catheter
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
“Lock” Therapy Defined
• Antimicrobial or antiseptic solution
instilled into the CVAD
• Dwells intraluminally; various times
• Commonly used antibiotics
• Prevention
– High risk patient populations
• Treatment
Dallas, TX • November 2–4, 2012
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
Donlan RM, CID 2011;52:1038
Dallas, TX • November 2–4, 2012
ABL Risks
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Antibiotic resistance
Stability of antimicrobials
Expense
Availability
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
Novel Catheter Lock
Strategies
• Chelating Agents
– Disodium or Tetrasodium EDTA
– Sodium Citrate
• Ethanol
• Biofilm Dispersants
• Bacteriophage
Donlan RM, CID 2011;52:1038
Dallas, TX • November 2–4, 2012
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 structure
Donlan RM, CID 2011;52:1038
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
Ethanol Lock
• Validated in human studies
• Action
– Antimicrobial
– Penetrates the extracellular polymeric
substance
– Denatures protein
Donlan RM, CID 2011;52:1038
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
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 types
Crinch CJ, Infect Control Hosp Epidemiol 2005;26:708
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
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, 2012
Electron micrograph of Bacteriophages Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
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
Dallas, TX • November 2–4, 2012
Dallas, TX • November 2–4, 2012