Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy

Antibiotics

Sarah J. Tennant¹  Donna R. Burgess¹  Jeffrey M. Rybak¹  Craig A. Martin¹  David S. Burgess²  Jerod Nagel³ 

[1] Pharmacy Services, University of Kentucky HealthCare, 800 Rose Street, H110, Lexington, KY 40536, USA; E-Mails:;College of Pharmacy, University of Kentucky, Biological Pharmaceutical Building, 789 S. Limestone Street, Lexington, KY 40536, USA; E-Mail:Pharmacy Services, University of Kentucky HealthCare, 800 Rose Street, H110, Lexington, KY 40536, USA;

关键词: antimicrobial stewardship;    pharmacodynamics;    Pseudomonas aeruginosa;    pharmacokinetics;    modeling;   

DOI  :  10.3390/antibiotics4040643

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.