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Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy

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 antipseu...

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Autores principales: Tennant, Sarah J., Burgess, Donna R., Rybak, Jeffrey M., Martin, Craig A., Burgess, David S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790317/
https://www.ncbi.nlm.nih.gov/pubmed/27025644
http://dx.doi.org/10.3390/antibiotics4040643
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author Tennant, Sarah J.
Burgess, Donna R.
Rybak, Jeffrey M.
Martin, Craig A.
Burgess, David S.
author_facet Tennant, Sarah J.
Burgess, Donna R.
Rybak, Jeffrey M.
Martin, Craig A.
Burgess, David S.
author_sort Tennant, Sarah J.
collection PubMed
description 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.
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spelling pubmed-47903172016-03-24 Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy Tennant, Sarah J. Burgess, Donna R. Rybak, Jeffrey M. Martin, Craig A. Burgess, David S. Antibiotics (Basel) Article 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. MDPI 2015-12-11 /pmc/articles/PMC4790317/ /pubmed/27025644 http://dx.doi.org/10.3390/antibiotics4040643 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tennant, Sarah J.
Burgess, Donna R.
Rybak, Jeffrey M.
Martin, Craig A.
Burgess, David S.
Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy
title Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy
title_full Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy
title_fullStr Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy
title_full_unstemmed Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy
title_short Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy
title_sort utilizing monte carlo simulations to optimize institutional empiric antipseudomonal therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790317/
https://www.ncbi.nlm.nih.gov/pubmed/27025644
http://dx.doi.org/10.3390/antibiotics4040643
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