title: Pharmacodynamic profiling of imipenem, meropenem and ertapenem against clinical isolates of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp. from Brazil.
abstract: The pharmacodynamic potency of imipenem, meropenem and ertapenem against extended-spectrum beta-lactamase (ESBL)-producing isolates was investigated. Minimal inhibitory concentration (MIC) determination, confirmation of ESBLs by Etest and the disk approximation test were performed for 133 ESBL-producing isolates of Escherichia coli and Klebsiella spp. Pharmacodynamic exposure, measured as percent of the dosing interval during which free drug was above the MIC (% fT>MIC), was modelled via a 5000-subject Monte Carlo simulation. Bactericidal cumulative fraction of response (CFR), defined as 40% fT>MIC, was calculated against each bacterial population. All agents achieved high bactericidal CFR against all ESBL isolates as a group, but ertapenem (96.26%) was slightly less effective than imipenem (99.96%) and meropenem (99.90%) (P<0.05). Similar results were observed against Klebsiella spp. only (P<0.05). Against E. coli, CFRs were close to 100%. Ertapenem is probably an effective agent against ESBL-producing bacteria, although its ability to achieve bactericidal pharmacodynamic exposures will depend on the bacterial susceptibility.
authors.affiliation: Fleury Institute, São Paulo, Brazil. carlos.kiffer@fleury.com.br
authors.forename: Carlos R V
authors.initials: CR
authors.lastname: Kiffer
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Kuti
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Eagye
authors.forename: Caio
authors.initials: C
authors.lastname: Mendes
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D001938:Brazil; D024901:Drug Resistance, Multiple, Bacterial; D000077727:Ertapenem; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D015378:Imipenem / Q000493:pharmacokinetics* / Q000494:pharmacology; D007709:Klebsiella / Q000187:drug effects / Q000201:enzymology / Q000302:isolation & purification / Q000378:metabolism*; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009010:Monte Carlo Method; D013845:Thienamycins / Q000493:pharmacokinetics* / Q000494:pharmacology; D001618:beta-Lactamases / Q000378:metabolism*; D047090:beta-Lactams / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D013845:Thienamycins; D047090:beta-Lactams; D015378:Imipenem; D001618:beta-Lactamases; D000077731:Meropenem; D000077727:Ertapenem