Pharmacodynamic profiling of imipenem, meropenem and ertapenem against clinical isolates of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp. from Brazil.
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.
Kiffer
Carlos R V
CR
Fleury Institute, São Paulo, Brazil. carlos.kiffer@fleury.com.br
Kuti
Joseph L
JL
Eagye
Kathryn J
KJ
Mendes
Caio
C
Nicolau
David P
DP
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
D013845:Thienamycins; D047090:beta-Lactams; D015378:Imipenem; D001618:beta-Lactamases; D000077731:Meropenem; D000077727:Ertapenem