Program Schedule

Beyond the Antibiogram: Using Monte Carlo Analysis to Optimize Institution-Specific Antipseudomonal Therapy

Session: Poster Abstract Session: PK/PD Studies
Thursday, October 9, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
  • IDweek-3.pdf (431.7 kB)
  • Background: Pseudomonas aeruginosa is the 5th most common pathogen implicated in nosocomial infections with increasing resistance to a limited arsenal of antibiotics. Monte Carlo Simulations (MCS) provide clinicians with an additional tool to guide empiric therapy by determining the probability that an antibiotic regimen will reach a certain pharmacodynamic target to optimize bactericidal activity. This study determined which antibiotic regimens will achieve a goal probability of target attainment (PTA) of 90% against P. aeruginosa at our institution.

    Methods: This study was a retrospective review of microbiological data from first cultures positive for P. aeruginosa at University of Kentucky HealthCare for 2012. Minimum inhibitory concentrations (MICs) for the following antibiotics were analyzed: aztreonam, cefepime, meropenem, and piperacillin/tazobactam administered via intermittent and prolonged infusion, amikacin, gentamicin, and tobramycin. Using MICs from UKHC specific isolates, and pharmacokinetic and pharmacodynamic parameters from previously published studies, a 10,000-subject MCS was run for each antimicrobial regimen to determine PTA.

    Results: Two-hundred seventy two isolates were included for analysis. For studied antibiotics against P. aeruginosa, the MIC50/MIC90 were 8/8 mcg/mL for amikacin, 8/32 mcg/mL for aztreonam, 4/16 mcg/mL for cefepime, 2/16 mcg/mL for gentamicin, 1/8 mcg/mL for meropenem, 8/128 mcg/mL for piperacillin/tazobactam, and 2/8 mcg/mL for tobramycin. None of the tested β-lactam regimens administered over 30 minutes reached a PTA > 90%.  Three-hour infusions of cefepime 2g every 8 hours, meropenem 1g every 8 hours, and meropenem 2g every 8 hours had a PTA of 93%, 92%, and 100%, respectively. Amikacin 25 mg/kg/day had a PTA of 94%.

    Conclusion: In patients with kinetics similar to healthy subjects, standard doses of β-lactam antibiotics administered via intermittent infusion do no reach PD targets against P. aeruginosa isolates at UK HC. Amikacin 25 mg/kg/day and some prolonged infusions of β-lactams achieved PD targets against P. aeruginosa. There are opportunities for further study to examine the clinical application of MCS in designing empiric antimicrobial therapy.

    Sarah Tennant, PharmD1, Jeffrey M. Rybak, PharmD1,2, Donna R. Burgess, RPh1, David S. Burgess, PharmD, FCCP3 and Craig Martin, PharmD4, (1)University of Kentucky HealthCare, Lexington, KY, (2)University of Kentucky Healthcare, Lexington, KY, (3)University of Kentucky, College of Pharmacy, Lexington, KY, (4)UK Healthcare, Lexington, KY


    S. Tennant, None

    J. M. Rybak, None

    D. R. Burgess, None

    D. S. Burgess, None

    C. Martin, None

    See more of: PK/PD Studies
    See more of: Poster Abstract Session

    Findings in the abstracts are embargoed until 12:01 a.m. EDT, Oct. 8th with the exception of research findings presented at the IDWeek press conferences.

    Sponsoring Societies:

    © 2014, All Rights Reserved.

    Follow IDWeek