Assessing the pharmacodynamic profile of intravenous antibiotics against prevalent Gram-negative organisms collected in Colombia

Assessing the pharmacodynamic profile of intravenous antibiotics against prevalent Gram-negative organisms collected in Colombia

Author Villegas, Maria Virginia Google Scholar
Briceno, David Felipe Google Scholar
Ruiz, Sory Jamil Google Scholar
Furtado, Guilherme Henrique Campos Autor UNIFESP Google Scholar
Nicolau, David P. Google Scholar
Institution Int Ctr Med Res & Training CIDEIM
CIDEIM
Hartford Hosp
Universidade Federal de São Paulo (UNIFESP)
Abstract Objectives: This study was designed to simulate standard and optimized dosing regimens for intravenous antibiotics against contemporary populations of Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa using MIC distribution data to determine which of the tested carbapenem regimens provided the greatest opportunity for obtaining maximal pharmacodynamic (PD) activity. Methods: The isolates studied were obtained from the COMPACT-COLOMBIA surveillance program conducted between February and November 2009. Antimicrobial susceptibility testing was conducted by broth microdilution method according to the CLSI guidelines. Doripenem, imipenem-cilastatin, and meropenem, were the modeled antibiotics. A 5,000 patient Monte Carlo simulation was performed for each regimen and PD targets were defined as free drug concentrations above the MIC for at least 40% of the dosing interval. Results: All carbapenem regimens obtained optimal exposures against E. coli, unlike the other Enterobacteriaceae tested. Against P. aeruginosa, only a prolonged infusion of doripenem exceeded the 90% cumulative fraction of response (CFR) threshold. Worrisomely, no regimens for any of the drugs tested obtained optimal CFR against A. baumannii. For P. aeruginosa intensive care unit (ICU) isolates, CFR was approximately 20% lower for isolates collected in the respiratory tract compared with bloodstream or intra-abdominal for imipenem and meropenem. Noteworthy, all doripenem and meropenem regimens achieved greater than 90% CFR against bloodstream and respiratory isolates of K. pneumoniae. Conclusions: Our data suggests that higher dosing and prolonged infusion of doripenem or meropenem may be suitable for empirically treating ICU P. aeruginosa, while none of the carbapenems achieved optimal cumulative fraction of response against A. baumannii. Standard dosing regimens of all the carbapenems tested achieved optimal CFR against E. coli isolates, but higher carbapenem dosages might be required for empiric treatment of K. pneumoniae, particularly from an intra-abdominal source. Non-standard dosage regimens studied in this modeling should be proven effective in prospective clinical trials.
Keywords drug resistance
bacterial
Gram-negative bacteria
Monte Carlo Method
Colombia
pharmacology
Language English
Sponsor Janssen-Cilag Pharmaceuticals
Merck
Wyeth
Baxter
Janssen-Cilag
Pfizer
MSD
AstraZeneca
Novartis
Merck Co., Inc
Johnson & Johnson Pharmaceuticals
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Date 2011-09-01
Published in Brazilian Journal Of Infectious Diseases. Salvador: Contexto, v. 15, n. 5, p. 413-419, 2011.
ISSN 1413-8670 (Sherpa/Romeo, impact factor)
Publisher Contexto
Extent 413-419
Origin http://dx.doi.org/10.1590/S1413-86702011000500001
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000295936600001
SciELO ID S1413-86702011000500001 (statistics in SciELO)
URI http://repositorio.unifesp.br/11600/42889

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