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

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dc.contributor.authorVillegas, Maria Virginia
dc.contributor.authorBriceno, David Felipe
dc.contributor.authorRuiz, Sory Jamil
dc.contributor.authorFurtado, Guilherme Henrique Campos [UNIFESP]
dc.contributor.authorNicolau, David P.
dc.contributor.institutionInt Ctr Med Res & Training CIDEIM
dc.contributor.institutionCIDEIM
dc.contributor.institutionHartford Hosp
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2018-06-15T14:04:34Z
dc.date.available2018-06-15T14:04:34Z
dc.date.issued2011-09-01
dc.description.abstractObjectives: 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.en
dc.description.affiliationInt Ctr Med Res & Training CIDEIM, Bacterial Resistance Grp, Cali 19225, Colombia
dc.description.affiliationCIDEIM, Bacterial Resistance Grp, Cali, Colombia
dc.description.affiliationHartford Hosp, Ctr Antiinfect Res & Dev, Hartford, CT 06115 USA
dc.description.affiliationUniv Fed Sao Paulo, Div Infect Dis, Hosp Sao Paulo, Sao Paulo, Brazil
dc.description.affiliationHartford Hosp, Div Infect Dis, Hartford, CT 06115 USA
dc.description.affiliationUnifespUniv Fed Sao Paulo, Div Infect Dis, Hosp Sao Paulo, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipJanssen-Cilag Pharmaceuticals
dc.description.sponsorshipMerck
dc.description.sponsorshipWyeth
dc.description.sponsorshipBaxter
dc.description.sponsorshipJanssen-Cilag
dc.description.sponsorshipPfizer
dc.description.sponsorshipMSD
dc.description.sponsorshipAstraZeneca
dc.description.sponsorshipNovartis
dc.description.sponsorshipMerck Co., Inc
dc.description.sponsorshipJohnson & Johnson Pharmaceuticals
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.format.extent413-419
dc.identifierhttp://dx.doi.org/10.1590/S1413-86702011000500001
dc.identifier.citationBrazilian Journal Of Infectious Diseases. Salvador: Contexto, v. 15, n. 5, p. 413-419, 2011.
dc.identifier.doi10.1590/S1413-86702011000500001
dc.identifier.fileS1413-86702011000500001.pdf
dc.identifier.issn1413-8670
dc.identifier.scieloS1413-86702011000500001
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/42889
dc.identifier.wosWOS:000295936600001
dc.language.isoeng
dc.publisherContexto
dc.relation.ispartofBrazilian Journal Of Infectious Diseases
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectdrug resistanceen
dc.subjectbacterialen
dc.subjectGram-negative bacteriaen
dc.subjectMonte Carlo Methoden
dc.subjectColombiaen
dc.subjectpharmacologyen
dc.titleAssessing the pharmacodynamic profile of intravenous antibiotics against prevalent Gram-negative organisms collected in Colombiaen
dc.typeinfo:eu-repo/semantics/article
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