Alternate Lock Solutions in Patients Receiving Parenteral Nutrition

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Alternate Lock Solutions in Patients Receiving
Parenteral Nutrition

• Deborah Andris MSN APNP
• Division of Colorectal Surgery
• Medical College of Wisconsin

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Objectives

• Discuss alternate catheter lock solutions for
  central venous access devices
• List potential usefulness in patients receiving
  long-term PN

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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

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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 19942711598 Orsi GB, Infect
Control Hosp Epidemiol 200223190
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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

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Impact of CLABSI in Home PN Patient

• 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

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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

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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 2011521038

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Intraluminal Colonization and Biofilms

• 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

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Intraluminal Colonization and Biofilms

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

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Antibiotics
Antibodies
Phagocytes
PROTECTION
Glycocalyx Enclosed Microcolony
ADHERENCE
Catheter Surface
NUTRIENT TRAPPING
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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

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

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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 198812185

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Lock Therapy Defined

• Antimicrobial or antiseptic solution instilled
  into the CVAD
• Dwells intraluminally various times
• Commonly used antibiotics
• Prevention
• High risk patient populations
• Treatment

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Current Use of ABL

• Recent literature review
• ABL effective
• High concentration of antibiotic
• Dwell times gt 12 h
• Duration of 14 days of treatment
• Optimal concentration and duration unknown
• Donlan RM, CID 2011521038

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ABL Risks

• Antibiotic resistance
• Stability of antimicrobials
• Expense
• Availability

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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

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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

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Novel Catheter Lock Strategies

• Chelating Agents
• Disodium or Tetrasodium EDTA
• Sodium Citrate
• Ethanol
• Biofilm Dispersants
• Bacteriophage
• Donlan RM, CID 2011521038

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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 2011521038

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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

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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 199725149
• Kite P, J Clin Microbiol 2004423073
• Percival S, Inf Control and Hosp Epidemiol
  200526515
• Bookstaver PB, Annals of Pharmacotherapy
  200943210

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Ethanol Lock

• Validated in human studies
• Action
• Antimicrobial
• Penetrates the extracellular polymeric substance
• Denatures protein
• Donlan RM, CID 2011521038

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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

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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
  2009301096

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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
  200526708

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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 2007642480

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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 200731302

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Clinical Research

• John, 2012
• Retrospective review
• 31 adult home PN patients with history of
  recurrent infection all on prophylactic locks
• PICCs 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 201236603

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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

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Bacteriophage

• Used in the 1920s and 1930s to treat bacterial
  infections
• Not validated in human studies
• Action
• Virus infects bacteria and injects its genetic
  material
• Antibacterial properties
• Degrades the EPS

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Bacteriophage

• Potential Application
• Decrease bacterial attachment
• Kill biofilm associated cells
• Eradicate the biofilm matrix
• Pretreatment of the catheter
• Lock therapy

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Electron micrograph of Bacteriophages
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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

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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/preventio
  n of CLABSI that avoid use of antibiotics
• New therapy goals
• eliminate biofilm
• prevent regrowth of organisms
• resolve patient symptoms

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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

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