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. © The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
CITATION STYLE
Zhanel, G. G., Baudry, P., Vashisht, V., Laing, N., Noreddin, A. M., & Hoban, D. J. (2008). Pharmacodynamic activity of ertapenem versus multidrug-resistant genotypically characterized extended-spectrum β-lactamase-producing Escherichia coli using an in vitro model. Journal of Antimicrobial Chemotherapy, 61(3), 643–646. https://doi.org/10.1093/jac/dkm533
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