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Antimicrobial Agents and Chemotherapy, January 2005, p. 276-280, Vol. 49, No. 1
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.1.276-280.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Pharmacodynamic Profile of Ertapenem against Klebsiella pneumoniae and Escherichia coli in a Murine Thigh Model

Dana Maglio,1 Mary Anne Banevicius,1 Christina Sutherland,1 Chinedum Babalola,1 Charles H. Nightingale,2 and David P. Nicolau1,3*

Center for Anti-Infective Research and Development,1 Office for Research Administration,2 Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut3

Received 29 April 2004/ Returned for modification 31 August 2004/ Accepted 25 September 2004

The pharmacodynamic profile of ertapenem was evaluated in a neutropenic mouse thigh infection model. Extended-spectrum beta-lactamase (ESBL)-positive and ESBL-negative clinical strains of Escherichia coli and Klebsiella pneumoniae were studied. MICs ranged from 0.0078 to 0.06 µg/ml with standard inoculum tests. Ertapenem doses were administered once to five times daily to achieve various exposures, reported as the percentage of the dosing interval that the concentration of free ertapenem was in excess of the MIC (%T>MICfree). Mean values for the static exposure and 80% maximally effective exposure (ED80) were 19% (range, 2 to 38%) and 33% (range, 13 to 65%) T>MICfree, respectively. Differences in exposure requirements based on the presence of an ESBL resistance mechanism or bacterial species were not evident. In addition, experiments using a 100-fold higher inoculum did not decrease the magnitude of the reduction in bacterial density from baseline achieved compared to lower-inoculum studies. The pharmacodynamic parameter of %T>MICfree correlated well with bactericidal activity for all isolates, and the static and ED80 exposures are consistent with those reported previously for carbapenems.

* Corresponding author. Mailing address: Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour St., Hartford, CT 06102. Phone: (860) 545-3940. Fax: (860) 545-3992. E-mail: dnicola{at}harthosp.org.

Antimicrobial Agents and Chemotherapy, January 2005, p. 276-280, Vol. 49, No. 1
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.1.276-280.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Eguchi, K., Kanazawa, K., Eriguchi, Y., Ueda, Y. (2009). Pharmacodynamics of SMP-601 (PTZ601) against Vancomycin-Resistant Enterococcus faecium and Methicillin-Resistant Staphylococcus aureus in Neutropenic Murine Thigh Infection Models. Antimicrob. Agents Chemother. 53: 3391-3398 [Abstract] [Full Text]  
  • 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. Antimicrob. Agents Chemother. 51: 1481-1486 [Abstract] [Full Text]  


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