This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xuan, D.
Right arrow Articles by Nicolau, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xuan, D.
Right arrow Articles by Nicolau, D.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, September 2002, p. 2990-2995, Vol. 46, No. 9
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.9.2990-2995.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Pharmacodynamic Assessment of Ertapenem (MK-0826) against Streptococcus pneumoniae in a Murine Neutropenic Thigh Infection Model

Dawei Xuan,1 Maryanne Banevicius,1 Blair Capitano,1 Myo-Kyoung Kim,1 Charles Nightingale,1,2 and David Nicolau1,3*

Department of Pharmacy Research,1 Division of Infectious Diseases,3 Office of Research Administration, Hartford Hospital, Hartford, Connecticut 061022

Received 21 August 2001/ Returned for modification 25 March 2002/ Accepted 10 May 2002

The objective of this study was to determine the susceptibility breakpoint of a new carbapenem, ertapenem (MK-0826), against Streptococcus pneumoniae strains based on bacterial density and survival studies in a murine thigh infection model. Sixteen S. pneumoniae isolates for which MICs ranged from 0.015 to 4.0 mg/liter were tested with neutropenic ICR mice. Animals were infected with bacteria at 105 to 106 CFU per thigh and were treated with ertapenem starting at 2 h postinfection for 4 days. Ertapenem was given subcutaneously at 50 mg/kg of body weight every 6 h, which simulates the human pharmacodynamic profile (in particular, the duration of time that the concentration of free drug remains above the MIC of 2 mg/liter). At 0 and 24 h postinfection, thighs were harvested for bacterial density determination. Survival was assessed during 4 days of therapy and 3 days after the therapy. A protein binding study was conducted with mice by use of the ultrafiltration method. Protein binding in mice was approximately 95%, which is comparable to that in humans. The average change in bacterial density ranged from -0.22 to -4.4 log CFU per thigh over 24 h compared to 0-h controls. The extent of microbial eradication was dependent on the MIC for the S. pneumoniae isolate. Substantial bactericidal activities (i.e., killing of approximately 2 log CFU per thigh) were consistently observed against isolates for which MICs were <=2 mg/liter, which also resulted in nearly 100% survival during the 4 days of drug dosing and 3 days after the therapy. Less-pronounced and highly variable bactericidal activities were detected against isolates for which the MIC was 4 mg/liter. Substantial enhancement in bactericidal activity was observed for CBA/J mice and is attributed to the contribution of the host defenses in the immunocompetent species. Assessment of the effectiveness of ertapenem by bacterial-density reduction over 24 h and by survival over 4 days of therapy in the murine thigh infection model reveals that the drug maintains maximal efficacy against S. pneumoniae isolates for which the MIC of this agent is <=2 mg/liter.

* Corresponding author. Mailing address: Division of Infectious Diseases, Hartford Hospital, 80 Seymour St., Hartford, CT 06102. Phone: (860) 545-3941. Fax: (860) 545-3992. E-mail: dnicola{at}harthosp.org.

Antimicrobial Agents and Chemotherapy, September 2002, p. 2990-2995, Vol. 46, No. 9
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.9.2990-2995.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • 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]  
  • Zhanel, G. G., Derkatch, S., Laing, N., Noreddin, A. M., Hoban, D. J. (2007). Pharmacodynamic activity of ertapenem versus penicillin-susceptible and penicillin-non-susceptible Streptococcus pneumoniae using an in vitro model. J Antimicrob Chemother 59: 144-147 [Abstract] [Full Text]  
  • Chen, M., Nafziger, A. N., Drusano, G. L., Ma, L., Bertino, J. S. Jr. (2006). Comparative pharmacokinetics and pharmacodynamic target attainment of ertapenem in normal-weight, obese, and extremely obese adults.. Antimicrob. Agents Chemother. 50: 1222-1227 [Abstract] [Full Text]  
  • Lemaire, S., Van Bambeke, F., Mingeot-Leclercq, M.-P., Tulkens, P. M. (2005). Activity of three {beta}-lactams (ertapenem, meropenem and ampicillin) against intraphagocytic Listeria monocytogenes and Staphylococcus aureus. J Antimicrob Chemother 55: 897-904 [Abstract] [Full Text]  
  • Maglio, D., Banevicius, M. A., Sutherland, C., Babalola, C., Nightingale, C. H., Nicolau, D. P. (2005). Pharmacodynamic Profile of Ertapenem against Klebsiella pneumoniae and Escherichia coli in a Murine Thigh Model. Antimicrob. Agents Chemother. 49: 276-280 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»