title: Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy.
abstract: Pseudomonas aeruginosa is a common pathogen implicated in nosocomial infections with increasing resistance to a limited arsenal of antibiotics. Monte Carlo simulation provides antimicrobial stewardship teams with an additional tool to guide empiric therapy. We modeled empiric therapies with antipseudomonal β-lactam antibiotic regimens to determine which were most likely to achieve probability of target attainment (PTA) of ≥90%. Microbiological data for P. aeruginosa was reviewed for 2012. Antibiotics modeled for intermittent and prolonged infusion were aztreonam, cefepime, meropenem, and piperacillin/tazobactam. Using minimum inhibitory concentrations (MICs) from institution-specific isolates, and pharmacokinetic and pharmacodynamic parameters from previously published studies, a 10,000-subject Monte Carlo simulation was performed for each regimen to determine PTA. MICs from 272 isolates were included in this analysis. No intermittent infusion regimens achieved PTA ≥90%. Prolonged infusions of cefepime 2000 mg Q8 h, meropenem 1000 mg Q8 h, and meropenem 2000 mg Q8 h demonstrated PTA of 93%, 92%, and 100%, respectively. Prolonged infusions of piperacillin/tazobactam 4.5 g Q6 h and aztreonam 2 g Q8 h failed to achieved PTA ≥90% but demonstrated PTA of 81% and 73%, respectively. Standard doses of β-lactam antibiotics as intermittent infusion did not achieve 90% PTA against P. aeruginosa isolated at our institution; however, some prolonged infusions were able to achieve these targets.
authors.affiliation: Pharmacy Services, University of Kentucky HealthCare, 800 Rose Street, H110, Lexington, KY 40536, USA. sarah.tennant@uky.edu.|College of Pharmacy, University of Kentucky, Biological Pharmaceutical Building, 789 S. Limestone Street, Lexington, KY 40536, USA. sarah.tennant@uky.edu.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Tennant
authors.affiliation: Pharmacy Services, University of Kentucky HealthCare, 800 Rose Street, H110, Lexington, KY 40536, USA. donna.burgess@uky.edu.|College of Pharmacy, University of Kentucky, Biological Pharmaceutical Building, 789 S. Limestone Street, Lexington, KY 40536, USA. donna.burgess@uky.edu.
authors.forename: Donna R
authors.initials: DR
authors.lastname: Burgess
authors.affiliation: Pharmacy Services, University of Kentucky HealthCare, 800 Rose Street, H110, Lexington, KY 40536, USA. jrybak@uthsc.edu.|College of Graduate Health Sciences, University of Tennessee, 920 Madison Avenue, Suite 407, Memphis, TN 38163, USA. jrybak@uthsc.edu.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Rybak
authors.affiliation: Pharmacy Services, University of Kentucky HealthCare, 800 Rose Street, H110, Lexington, KY 40536, USA. cmart2@uky.edu.|College of Pharmacy, University of Kentucky, Biological Pharmaceutical Building, 789 S. Limestone Street, Lexington, KY 40536, USA. cmart2@uky.edu.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Martin
authors.affiliation: College of Pharmacy, University of Kentucky, Biological Pharmaceutical Building, 789 S. Limestone Street, Lexington, KY 40536, USA. david.burgess@uky.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Burgess
keywords: Pseudomonas aeruginosa; antimicrobial stewardship; modeling; pharmacodynamics; pharmacokinetics