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Bactericidal activities of meropenem and ertapenem against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a neutropenic mouse thigh model.
Antimicrob Agents Chemother. 2007 Apr; 51(4):1481-6.AA

Abstract

The purpose of this study was to examine the in vivo efficacies of meropenem and ertapenem against extended-spectrum-beta-lactamase (ESBL)-producing isolates with a wide range of MICs. Human-simulated dosing regimens in mice were designed to approximate the free drug percent time above the MIC (fT>MIC) observed for humans following meropenem at 1 g every 8 h and ertapenem at 1 g every 24 h. An in vivo neutropenic mouse thigh infection model was used to examine the bactericidal effects against 31 clinical ESBL Escherichia coli and Klebsiella pneumoniae isolates and 2 non-ESBL isolates included for comparison at a standard 10(5) inoculum. Three isolates were examined at a high 10(7) inoculum as well. Meropenem displayed greater in vitro potency, with a median MIC (range) (microg/ml) of 0.125 (0.03 to 32), than did ertapenem, with 0.5 (0.012 to 128). Seven of the 31 ESBL isolates were removed from the efficacy analysis due to their inability to establish infection in the mouse model. When MICs were<or=1.5 microg/ml for ertapenem (<or=0.5 microg/ml for meropenem), similar reductions in CFU (approximately 2-log kill) were observed for both ertapenem (fT>MIC>or=23%) and meropenem (fT>MIC>or=75%). Ertapenem showed bacterial regrowth for seven of eight isolates, with MICs of>or=2 microg/ml (fT>MIC<or=20%), while meropenem displayed antibacterial potency that varied from a static effect to a 1-log bacterial reduction in these isolates (fT>MIC=30 to 65%). At a 10(7) inoculum, both agents eradicated bacteria due to adequate exposures (fT>MIC=20 to 45%). Due to low MICs, no difference in bacterial kill was noted for the majority of ESBL isolates tested. However, for isolates with raised ertapenem MICs of>or=2 microg/ml, meropenem displayed sustained efficacy due to its greater in vitro potency and higher resultant fT>MIC.

Authors+Show Affiliations

Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA, and Department of Infectious Disease, Peking Union Medical College Hospital, Beijing, China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17283197

Citation

DeRyke, C Andrew, et al. "Bactericidal Activities of Meropenem and Ertapenem Against Extended-spectrum-beta-lactamase-producing Escherichia Coli and Klebsiella Pneumoniae in a Neutropenic Mouse Thigh Model." Antimicrobial Agents and Chemotherapy, vol. 51, no. 4, 2007, pp. 1481-6.
DeRyke CA, Banevicius MA, Fan HW, et al. Bactericidal activities of meropenem and ertapenem against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a neutropenic mouse thigh model. Antimicrob Agents Chemother. 2007;51(4):1481-6.
DeRyke, C. A., Banevicius, M. A., Fan, H. W., & Nicolau, D. P. (2007). Bactericidal activities of meropenem and ertapenem against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a neutropenic mouse thigh model. Antimicrobial Agents and Chemotherapy, 51(4), 1481-6.
DeRyke CA, et al. Bactericidal Activities of Meropenem and Ertapenem Against Extended-spectrum-beta-lactamase-producing Escherichia Coli and Klebsiella Pneumoniae in a Neutropenic Mouse Thigh Model. Antimicrob Agents Chemother. 2007;51(4):1481-6. PubMed PMID: 17283197.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bactericidal activities of meropenem and ertapenem against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a neutropenic mouse thigh model. AU - DeRyke,C Andrew, AU - Banevicius,Mary Anne, AU - Fan,Hong Wei, AU - Nicolau,David P, Y1 - 2007/02/05/ PY - 2007/2/7/pubmed PY - 2007/8/2/medline PY - 2007/2/7/entrez SP - 1481 EP - 6 JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 51 IS - 4 N2 - The purpose of this study was to examine the in vivo efficacies of meropenem and ertapenem against extended-spectrum-beta-lactamase (ESBL)-producing isolates with a wide range of MICs. Human-simulated dosing regimens in mice were designed to approximate the free drug percent time above the MIC (fT>MIC) observed for humans following meropenem at 1 g every 8 h and ertapenem at 1 g every 24 h. An in vivo neutropenic mouse thigh infection model was used to examine the bactericidal effects against 31 clinical ESBL Escherichia coli and Klebsiella pneumoniae isolates and 2 non-ESBL isolates included for comparison at a standard 10(5) inoculum. Three isolates were examined at a high 10(7) inoculum as well. Meropenem displayed greater in vitro potency, with a median MIC (range) (microg/ml) of 0.125 (0.03 to 32), than did ertapenem, with 0.5 (0.012 to 128). Seven of the 31 ESBL isolates were removed from the efficacy analysis due to their inability to establish infection in the mouse model. When MICs were<or=1.5 microg/ml for ertapenem (<or=0.5 microg/ml for meropenem), similar reductions in CFU (approximately 2-log kill) were observed for both ertapenem (fT>MIC>or=23%) and meropenem (fT>MIC>or=75%). Ertapenem showed bacterial regrowth for seven of eight isolates, with MICs of>or=2 microg/ml (fT>MIC<or=20%), while meropenem displayed antibacterial potency that varied from a static effect to a 1-log bacterial reduction in these isolates (fT>MIC=30 to 65%). At a 10(7) inoculum, both agents eradicated bacteria due to adequate exposures (fT>MIC=20 to 45%). Due to low MICs, no difference in bacterial kill was noted for the majority of ESBL isolates tested. However, for isolates with raised ertapenem MICs of>or=2 microg/ml, meropenem displayed sustained efficacy due to its greater in vitro potency and higher resultant fT>MIC. SN - 0066-4804 UR - https://www.unboundmedicine.com/medline/citation/17283197/Bactericidal_activities_of_meropenem_and_ertapenem_against_extended_spectrum_beta_lactamase_producing_Escherichia_coli_and_Klebsiella_pneumoniae_in_a_neutropenic_mouse_thigh_model_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&amp;pmid=17283197 DB - PRIME DP - Unbound Medicine ER -