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 Nicolau, D. P.
Right arrow Articles by Nightingale, C. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nicolau, D. P.
Right arrow Articles by Nightingale, C. H.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 2000, p. 1291-1295, Vol. 44, No. 5
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Pharmacodynamic Assessment of Cefprozil against Streptococcus pneumoniae: Implications for Breakpoint Determinations

David P. Nicolau,1,2,* Cyprian O. Onyeji,1 Mingkang Zhong,1 Pamela R. Tessier,1 Mary Anne Banevicius,1 and Charles H. Nightingale3

Department of Pharmacy Research1 and Division of Infectious Diseases,2 Office of Research Administration,3 Hartford Hospital, Hartford, Connecticut 06102

Received 7 July 1999/Returned for modification 12 September 1999/Accepted 10 February 2000

Cefprozil, an oral semisynthetic cephalosporin, is commonly utilized in the treatment of respiratory-tract infections in children. While this agent has provided acceptable clinical success over a number of years, this study was undertaken to better define its pharmacodynamic profile against Streptococcus pneumoniae. Nineteen clinical isolates of S. pneumoniae were utilized in the neutropenic murine thigh infection model. To simulate the pharmacokinetic profile of cefprozil in children, the renal function of mice was impaired with uranyl nitrate, and a commercially available cefprozil suspension (6 mg/kg of body weight) was administered orally every 12 h. Mice were infected with 106 to 107 CFU per thigh, and therapy was initiated 2 h later. At 0 and 24 h postinfection, thighs were harvested to determine bacterial density. Survival was assessed during 96 h of therapy. The magnitude of bacterial kill ranged from 0.5 to 4.4 log10 CFU per thigh over 24 h, and the extent of microbial eradication was dependent on the MIC. Killing of more than 2.6 log10 CFU per thigh was observed with MICs of <= 3 µg/ml, while either minimal killing or growth was detected with MICs of >= 4 µg/ml. Mortality in untreated control animals was 100%. Animals infected with strains for which the MICs were <= 2 µg/ml survived the infection, whereas MICs exceeding 2 µg/ml resulted in substantial mortality. These studies demonstrate the effectiveness of cefprozil against isolates of the pneumococcus for which the MICs are <= 2 µg/ml using a drug exposure typically observed in children. These data support a susceptibility breakpoint of <= 2 µg/ml for cefprozil.

* Corresponding author. Mailing address: Division of Infectious Diseases, Hartford Hospital, 80 Seymour St., Hartford, CT 06102. Phone: (860) 545-3941. Fax: (860) 545-5112. E-mail: dnicola{at}harthosp.org.

Antimicrobial Agents and Chemotherapy, May 2000, p. 1291-1295, Vol. 44, No. 5
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Tam, V. H., Schilling, A. N., Poole, K., Nikolaou, M. (2007). Mathematical modelling response of Pseudomonas aeruginosa to meropenem. J Antimicrob Chemother 60: 1302-1309 [Abstract] [Full Text]  
  • Andes, D., Craig, W. A. (2006). Pharmacodynamics of a New Cephalosporin, PPI-0903 (TAK-599), Active against Methicillin-Resistant Staphylococcus aureus in Murine Thigh and Lung Infection Models: Identification of an In Vivo Pharmacokinetic-Pharmacodynamic Target.. Antimicrob. Agents Chemother. 50: 1376-1383 [Abstract] [Full Text]  
  • Tam, V. H., Schilling, A. N., Neshat, S., Poole, K., Melnick, D. A., Coyle, E. A. (2005). Optimization of Meropenem Minimum Concentration/MIC Ratio To Suppress In Vitro Resistance of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 49: 4920-4927 [Abstract] [Full Text]  
  • Yershov, A. L., Jordan, B. S., Guymon, C. H., Dubick, M. A. (2005). Relationship between the inoculum dose of Streptococcus pneumoniae and pneumonia onset in a rabbit model. Eur Respir J 25: 693-700 [Abstract] [Full Text]  
  • Nicolau, D. P., Mattoes, H. M., Banevicius, M., Xuan, D., Nightingale, C. H. (2003). Pharmacodynamics of a Novel Des-F(6)-Quinolone, BMS-284756, against Streptococcuspneumoniae in the Thigh Infection Model. Antimicrob. Agents Chemother. 47: 1630-1635 [Abstract] [Full Text]  
  • Kerrn, M. B., Frimodt-Moller, N., Espersen, F. (2003). Effects of Sulfamethizole and Amdinocillin against Escherichia coli Strains (with Various Susceptibilities) in an Ascending Urinary Tract Infection Mouse Model. Antimicrob. Agents Chemother. 47: 1002-1009 [Abstract] [Full Text]  
  • Xuan, D., Banevicius, M., Capitano, B., Kim, M.-K., Nightingale, C., Nicolau, D. (2002). Pharmacodynamic Assessment of Ertapenem (MK-0826) against Streptococcuspneumoniae in a Murine Neutropenic Thigh Infection Model. Antimicrob. Agents Chemother. 46: 2990-2995 [Abstract] [Full Text]  
  • Mattoes, H. M., Banevicius, M., Li, D., Turley, C., Xuan, D., Nightingale, C. H., Nicolau, D. P. (2001). Pharmacodynamic Assessment of Gatifloxacin against Streptococcus pneumoniae. Antimicrob. Agents Chemother. 45: 2092-2097 [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»