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Antimicrobial Agents and Chemotherapy, April 2007, p. 1481-1486, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.00752-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Bactericidal Activities of Meropenem and Ertapenem against Extended-Spectrum-ß-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in a Neutropenic Mouse Thigh Model{triangledown}

C. Andrew DeRyke,1 Mary Anne Banevicius,1 Hong Wei Fan,1,3 and David P. Nicolau1,2*

Center for Anti-Infective Research and Development,1 Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut 06102,2 Department of Infectious Disease, Peking Union Medical College Hospital, Beijing 100730, China3

Received 21 June 2006/ Returned for modification 31 October 2006/ Accepted 25 January 2007

The purpose of this study was to examine the in vivo efficacies of meropenem and ertapenem against extended-spectrum-ß-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 105 inoculum. Three isolates were examined at a high 107 inoculum as well. Meropenem displayed greater in vitro potency, with a median MIC (range) (µg/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 ≤1.5 µg/ml for ertapenem (≤0.5 µg/ml for meropenem), similar reductions in CFU ({approx} 2-log kill) were observed for both ertapenem (fT>MIC ≥ 23%) and meropenem (fT>MIC ≥ 75%). Ertapenem showed bacterial regrowth for seven of eight isolates, with MICs of ≥2 µg/ml (fT>MIC ≤ 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 107 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 ≥2 µg/ml, meropenem displayed sustained efficacy due to its greater in vitro potency and higher resultant fT>MIC.

* Corresponding author. Mailing address: Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102. Phone: (860) 545-3941. Fax: (860) 545-3992. E-mail: dnicola{at}harthosp.org

{triangledown} Published ahead of print on 5 February 2007.

Antimicrobial Agents and Chemotherapy, April 2007, p. 1481-1486, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.00752-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • 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 {beta}-lactamase-producing Escherichia coli using an in vitro model. J Antimicrob Chemother 61: 643-646 [Abstract] [Full Text]  


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