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Antibiotics 2015, 4(4), 643-652;

Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy

Pharmacy Services, University of Kentucky HealthCare, 800 Rose Street, H110, Lexington, KY 40536, USA
College of Pharmacy, University of Kentucky, Biological Pharmaceutical Building, 789 S. Limestone Street, Lexington, KY 40536, USA
College of Graduate Health Sciences, University of Tennessee, 920 Madison Avenue, Suite 407, Memphis, TN 38163, USA
These authors contributed equally to this work.
This work was completed while Dr. Rybak was a trainee at University of Kentucky HealthCare.
Author to whom correspondence should be addressed.
Academic Editors: Jerod Nagel and Angela Huang
Received: 29 September 2015 / Revised: 24 November 2015 / Accepted: 3 December 2015 / Published: 11 December 2015
(This article belongs to the Special Issue Antimicrobial Stewardship)
Full-Text   |   PDF [709 KB, uploaded 11 December 2015]   |  


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. View Full-Text
Keywords: antimicrobial stewardship; pharmacodynamics; Pseudomonas aeruginosa; pharmacokinetics; modeling antimicrobial stewardship; pharmacodynamics; Pseudomonas aeruginosa; pharmacokinetics; modeling

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Tennant, S.J.; Burgess, D.R.; Rybak, J.M.; Martin, C.A.; Burgess, D.S. Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy. Antibiotics 2015, 4, 643-652.

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