Beyond the Antibiogram: Using Monte Carlo Analysis to Optimize Institution-Specific Antipseudomonal Therapy
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.
D. R. Burgess, None
D. S. Burgess, None
C. Martin, None