CONFLICT OF INTEREST ANTIMICROBIAL LOCK SOLUTIONS INCREASE BACTEREMIA

Transcription

1 CONFLICT OF INTEREST ANTIMICROBIAL LOCK SOLUTIONS INCREASE BACTEREMIA NONE Vandana Dua Niyyar, MD Associate Professor of Medicine, Division of Nephrology, Emory University. OBJECTIVES Role of biofilm in CRB Antimicrobial locks in the management of CRB Are they effective? Are they safe? ROLE OF BIOFILM Predisposing factors for biofilm formation A source of bacterial contamination Intra-luminal A foreign surface for bacterial adherence Catheter A fluid environment Blood Dasgupta. Biofilms and Infection in Dialysis Patients. Seminars In Dialysis 2002 Bacterial contact with a foreign surface Irreversible adherence of bacteria Bacterial proliferation Biofilm generated Coating of exo-polysaccharide Sticky glycocalyx matrix Dasgupta. Biofims and Infection in Dialysis Patients.Seminars In Dialysis

2 BIOFILMS: Shield bacteria and prevents diffusion of antibiotics Promote resistance to antibiotics (altered phenotype) BIOFILMS: May be eradicated by the use of highly concentrated solutions of antibiotics Antibiotic concentration should exceed the MIC needed for bactericidal effect Antimicrobial locks should be used in conjunction with systemic antibiotics Dasgupta. Biofims and Infection in Dialysis Patients. Seminars In Dialysis 2002 CATHETER LOCK SOLUTIONS ANTI-MICROBIAL Antiseptic Inhibits the growth of microorganisms NO development of resistance Antibiotic Kills microorganisms May induce resistant strains FOR TREATMENT OF CRB Anti-microbial locks may be used for eradication of CRB to attempt to preserve vascular access sites Clinical success highly dependent on bacterial pathogen 87% for gram negative 40% for Staphylococcus aureus Short follow-up Small sample sizes Potential for systemic toxicity Potential for resistance Poole et al. Treatment of CRB with abx lock protocol: effect of bacterial pathogen. NDT

3 All patients with CRB Receive systemic antibiotics Are already exposed to an increased risk of developing subsequent resistant organisms To determine the additional risk associated with antimicrobial locks, comparison should be Systemic abx alone Systemic abx and AML Observational retrospective cohort study Treatment Systemic Vancomycin + Gentamicin Antimicrobial Lock Solution Controls (n=265 positive blood cultures) Yes No Study Group (n=662 positive blood cultures) Yes Vancomycin 10 mg Gentamicin 8 mg Heparin 5000 units/ml Aims Incidence of CRB Incidence of anti-microbial resistance Study end-points Need for catheter removal Relapse rates Culture of anti-microbial resistant organisms BUT Incidence of CRB (8.50 to 3.80/1000 catheter days) 3

4 CHANGING PATTERNS INCREASED RESISTANCE Controls (n=265) Systemic antibiotics only Study Group (n=662) Systemic antibiotics and antimicrobial locks P-value Relapses 13.2% 6.8% Gram Positive 64.5% 76.1% < Gram Negative 33.2% 23.3% < Increased gentamicin resistance in Gram negative organisms Enterobacter species resistant to gentamicin and ciprofloxacin CLINICAL IMPLICATIONS Most important predictor of early treatment failure Organism isolated Increased incidence of highly pathogenic organisms like Staphylococcus aureus and gentamicin-resistant Enterobacter Increased complications Increased mortality Limitations Retrospective nature of study Unaddressed confounding factors Change in microbial profile over time No control for correlated data Once a patient gets a CRB, more likely to get infected again SUMMARY Antimicrobial catheter lock solutions may potentially colonization biofilm formation the risk of catheter related bacteremia Antibiotic lock solutions concerning for Systemic side effects Potential for drug resistance SUMMARY Well-designed, long-term randomized controlled trials needed to establish safety and efficacy Best prophylaxis Minimize catheter use 4

5 SUMMARY The greatest risk.to human health comes in the form of antibiotic-resistant bacteria. We live in a bacterial world where we will never be able to stay ahead of the mutation curve. A test of our resilience is just how far behind the curve we allow ourselves to fall. World Economic Forum THANK YOU! Spellberg et al. The Future of Antibiotics And Resistance. NEJM 2013; 368: CATHETER LOCK SOLUTIONS EFFECT ON BIOFILM FOR OF CRB Heparin induces biofilm formation in the presence of Staphylococcus aureus Shanks et al. Catheter lock solutions influence biofilm formation. NDT 2006 CATHETER LOCK SOLUTIONS EFFECT ON BIOFILM Antimicrobial catheter lock solutions may potentially colonization biofilm formation the risk of catheter related bacteremia Antibiotic lock solutions concerning for Systemic side effects Potential for drug resistance Jones et al. Biofilm characterization in Tunneled HD catheters. AJKD

6 Meta-analysis of 7 trials 819 catheters in 624 patients 5 studies - antibiotic lock 1-30% citrate 1 - taurolidine 7.72 X less risk of catheter-related bacteremia as compared to heparin Jaffer et al. A meta-analysis of catheter locking solutions in prevention of CRB. AJKD 2008 Allon. Prophylaxis against CRB a glimmer of hope. AJKD 2008 Short follow-up of the original studies Potential for systemic toxicity Potential for resistance Economic ramifications Regulatory issues None are FDA approved Another meta-analysis evaluated 8 RCTs 3 X less risk of catheter-related bacteremia as compared to heparin BUT Achieved incidence of CRB in the groups with antimicrobial catheter locks was similar to published reports from HD units With low CRB incidence And presumably stricter hygienic measures Allon. Prophylaxis against CRB a glimmer of hope. AJKD 2008 Bleyer AJ. Use of antimicrobial catheter lock solutions to prevent CB. CJASN 2007 Recommended Intensifying the education of all dialysis staff on adequate catheter care Reserving antibiotic lock solutions for patients At high-risk of infection Or those in whom a catheter-related bacteremia would have devastating consequences Bleyer AJ. Use of antimicrobial catheter lock solutions to prevent CRB. CJASN