280. Empirical Combination Antimicrobial Therapy for Bloodstream Infections (BSI) in an Intensive Care Unit (ICU) Setting: Using Pharmacodynamics (PD) to Make Predictions
Session: Poster Abstract Session: Antimicrobial Therapy: Clinical Studies
Friday, October 21, 2011
Room: Poster Hall B1
Handouts
  • 280_MaryTarka.pdf (1.2 MB)
  • Background: Although Monte Carlo Simulation (MCS) methods have been extensively used to predict the PD of single antimicrobials, data for combination therapies commonly used in clinical practice are scarce. Our goal was to conduct PD analyses of antibiotic combinations as empirical therapy for BSI in an ICU population.
    Methods: Using 2007-2010 CANWARD (ongoing national surveillance study assessing antimicrobial resistance in Canadian hospitals) data, ICU pathogens isolated from blood were identified and antimicrobial activity (broth dilution) was determined. Coagulase negative staphylococcus and fungi were excluded. Using MCS, population pharmacokinetics were applied to study cohorts (n=5,000), 70.0 + 9.9 kg, Clcr 60-120 mL/min. Cefepime (Cef, 2 g q6h), ciprofloxacin (Cip, 400 mg q8h), meropenem (Mer, 2 g q8h) and piperacillin-tazobactam (PT, 4.5 g q6h) were tested alone and in combination with vancomycin (Van, 1 g q8-12h) or linezolid (Lin 600 mg q12h) for enhanced Gram-positive coverage. MIC distributions were used to determine cumulative target attainment (CTA) or % achieving ƒT>MIC >50% for Cef, Mer and PT, AUC24/MIC >125 for Cip, AUC/MIC >400 for Van and AUC/MIC >80 for Lin. An acceptable CTA was defined as achieving PD target in at least 90% of the population.
    Results: 1,015 BSI pathogens were characterized with 23.6% S. aureus (including 5.9% MRSA), 22.0% E. coli, 14.3% Enterococcus spp (including 10.0% E. faecalis), 14.0% Klebsiella spp, 9.8% P. aeruginosa and 7.6% Enterobacter spp. CTA was 85%, 80%, 74% and 54% for Mer, PT, Cef and Cip alone, respectively. CTA was increased to 94% for Mer-Van, 89% for PT-Van, 96% for Cef-Van and 83% for Cip-Van. In comparison, CTA was 92%, 87%, 93% and 76%, respectively, for combinations with Lin. 
    Conclusion: As empirical therapy for BSI in ICU patients, meropenem or cefepime in combination with either vancomycin or linezolid reached PD targets in at least 90% of the population. Niether piperacillin-tazobactam nor ciprofloxacin achieved acceptable target attainment even when administered at the highest recommended doses and in combination with either vancomycin or linezolid.

    Subject Category: A. Antimicrobial agents and Resistance

    Sheryl Zelenitsky, PharmD, Pharmacy, University of Manitoba, Winnipeg, MB, Canada, Robert Ariano, PharmD, Pharmacy, St. Boniface General Hospital, Winnipeg, MB, Canada, Anand Kumar, MD, Internal Medicine and Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada and George G. Zhanel, PhD, Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada

    Disclosures:

    S. Zelenitsky, Pfizer Canada Inc.: Research, Research support

    R. Ariano, None

    A. Kumar, Pfizer Canada Inc.: Research, Research support

    G. G. Zhanel, Abbott Laboratories Ltd.: Research, Research support
    Astellas Pharma Canada Inc.: Research, Research support
    Bayer Schering Pharma : Research, Research support
    Merck Frosst Canada Ltd.: Research, Research support
    Pfizer Canada Inc.: Research, Research support
    Sepracor Pharmaceuticals Inc.: Research, Research support
    The Medicines Company: Research, Research support

    Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.