1837. Unit-specific Pharmacodynamic Modelling to Aid in Empiric Therapy Selection
Session: Poster Abstract Session: Treatment of HAIs/Antimicrobial Resistant Infections
Saturday, October 10, 2015
Room: Poster Hall
  • MCS poster FINAL.pdf (580.2 kB)
  • Background: Antibiograms are an important tool to determine appropriate empiric therapy based on local resistance patterns; however, antibiograms ignore the impact of pharmacodynamics (PD) in relation to the underlying MIC distribution. The purpose of this study was to explore differences in PD target attainment between multiple critical care units with different MIC distributions.

    Methods: Antimicrobial MIC results via Phoenix® and Etest® for Enterobacteriaceae and Pseudomonas aeruginosa isolates were obtained from the clinical microbiology laboratory and processed into unit-specific antibiograms. MIC distributions for aztreonam (ATM), cefepime (CFP), meropenem (MEM), and piperacillin/tazobactam (PTZ) were generated from the data. Pharmacokinetic parameters for each agent were derived from healthy subject literature. PD target attainment was modelled utilizing Monte Carlo Simulations for 4 different critical care units (Cardiovascular [CVICU], Medical [MICU], Neurosurigical [NSICU], and Surgical/Trauma [SICU]). Desired %fT>MIC was 40% for MEM, 50% for PTZ, and 60% for ATM and CFP.

    Results: 508 isolates (103 P. aeruginosa and 405 Enterobacteriaceae) across 4 units were included. SICU had the most isolates (178) and Enterobacteriaceae (150) isolates, while MICU had the most P. aeruginosa (38) isolates. In general, ATM had the lowest probability of achieving the PD target when compared to the other agents. All CFP and MEM regimens evaluated against Enterobacteriaceae were predicted to achieve the PD target >90% of the time. In contrast, CFP and MEM at 2g q8h prolonged infusion over 3 hours against P. aeruginosa were predicted to achieve the PD target >90% of the time in the NSICU, but not in other units. Decreases in overall PD target attainment for all agents were driven by P. aeruginosa MICs, as probability of target attainment was significantly higher for Enterobacteriaceae across all regimens and units. Prolonged infusion regimens outperformed the equivalent bolus regimen for each corresponding drug regimen.

    Conclusion: Differing MIC distributions among critical care units may lead to different optimal antimicrobial dosing regimens to achieve the desired PD target. Empiric beta-lactam monotherapy may be inadequate for P. aeruginosa infections in critical care units.

    W. Cliff Rutter, PharmD1, Donna R. Burgess, RPh2 and David S. Burgess, PharmD, FCCP1, (1)University of Kentucky, College of Pharmacy, Lexington, KY, (2)University of Kentucky HealthCare, Lexington, KY


    W. C. Rutter, None

    D. R. Burgess, None

    D. S. Burgess, None

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.