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- Title
Pharmacodynamic activity of ertapenem versus multidrug-resistant genotypically characterized extended-spectrum {beta}-lactamase-producing Escherichia coli using an in vitro model.
- Authors
George G. Zhanel; Patricia Baudry; Vibhu Vashisht; Nancy Laing; Ayman M. Noreddin; Daryl J. Hoban
- Abstract
: Background This study assessed the pharmacodynamic activity of ertapenem against multidrug-resistant (MDR) genotypically characterized extended-spectrum β-lactamase (ESBL)-producing Escherichia coli using an in vitro model. : Methods Six ESBL-producing E. coli with the CTX-M-15 genotype were studied. All six strains were MDR (defined as resistance to third-generation cephalosporins and ≥two other unrelated antimicrobial classes). The in vitro pharmacodynamic model was inoculated with 1 × 106 cfu/mL, and ertapenem was dosed once daily at 0 and 24 h to simulate free (f) Cmax and t1/2 obtained after a standard 1 g intravenous once-daily dose in healthy volunteers (fCmax, 15 mg/L; t1/2, 4 h). Sampling was performed over 48 h to assess viable growth and resistance selection. : Results Ertapenem T>MIC ≥98% (ertapenem MICs ≤0.25 mg/L) resulted in bactericidal (≥3 log10 killing) activity at 6, 12, 24 and 48 h against all strains. Eradication of organisms from the in vitro model (below the level of detection) occurred at 2 h followed by slow regrowth of the majority of the strains (5 of 6) over 12, 24 and 48 h time points. Despite limited regrowth, ertapenem achieved a bactericidal effect against all strains (all time points) over the 48 h study period. : Conclusions Ertapenem was rapidly bactericidal (in ∼2 h) against MDR ESBL (CTX-M-15)-producing E. coli (ertapenem MICs ≤0.25 mg/L) when simulating free drug after 1 g intravenous once-daily dosing. This bactericidal activity was maintained over the 48 h experimental period with only minor regrowth, which was not associated with MIC increase from baseline.
- Subjects
DRUG resistance in microorganisms; ESCHERICHIA coli; CEPHALOSPORINS; LACTAMS
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2008, Vol 61, Issue 3, p643
- ISSN
0305-7453
- Publication type
Article
- DOI
10.1093/jac/dkm533