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 Azoulay-Dupuis, E.
Right arrow Articles by Köhler, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Azoulay-Dupuis, E.
Right arrow Articles by Köhler, T.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2004, p. 765-773, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.765-773.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Activities of Garenoxacin against Quinolone-Resistant Streptococcus pneumoniae Strains In Vitro and in a Mouse Pneumonia Model

E. Azoulay-Dupuis,1* J. P. Bédos,1 J. Mohler,1 G. Peytavin,1 R. Isturiz,1 P. Moine,1 V. Rieux,1 C. Cherbuliez,2 J. C. Péchère,2 B. Fantin,1 and T. Köhler2

INSERM EMI-9933, Faculté de Médecine Xavier Bichat, Paris, France,1 Department of Microbiology, University of Geneva, Geneva, Switzerland2

Received 20 February 2003/ Returned for modification 16 July 2003/ Accepted 18 November 2003

Garenoxacin is a novel des-F(6) quinolone with enhanced in vitro activities against both gram-positive and gram-negative bacteria. We compared the activity of garenoxacin with that of trovafloxacin (TVA) against Streptococcus pneumoniae, together with their efficacies and their capacities to select for resistant mutants, in a mouse model of acute pneumonia. In vitro, garenoxacin was more potent than TVA against wild-type S. pneumoniae and against a mutant with a single mutation (parC), a mutant with double mutations (gyrA and parC), and a mutant with triple mutations (gyrA, parC, and parE). Swiss mice were infected with 105 CFU of virulent, encapsulated S. pneumoniae strain P-4241 or its derived isogenic parC, gyrA, gyrA parC, and efflux mutants and 107 CFU of poorly virulent clinical strains carrying a parE mutation or gyrA, parC, and parE mutations. The drugs were administered six times, every 12 h, beginning at either 3 or 18 h postinfection. The pulmonary pharmacokinetic parameters in mice infected with strain P-4241 and treated with garenoxacin or TVA (25 mg/kg of body weight) were as follows: maximum concentration of drug in serum (Cmax; 17.3 and 21.2 µg/ml, respectively), Cmax/MIC ratio (288 and 170, respectively), area under the concentration-time curve (AUC; 48.5 and 250 µg · h/ml, respectively), and AUC/MIC ratio (808 and 2,000, respectively). Garenoxacin at 25 and 50 mg/kg was highly effective (survival rates, 85 to 100%) against the wild-type strain and mutants harboring a single mutation. TVA was as effective as garenoxacin against these strains. TVA at 200 mg/kg and garenoxacin at 50 mg/kg were ineffective against the mutant with the parC and gyrA double mutations and the mutant with the gyrA, parC, and parE triple mutations. The efficacy of garenoxacin was reduced only when strains bore several mutations for quinolone resistance.

* Corresponding author. Mailing address: INSERM EMI-U 9933, Faculté Xavier Bichat, 16 rue Henri Huchard, 75870 Paris Cedex 18, France. Phone: (33) 1 44 85 61 53. Fax: (33) 1 44 85 61 47. E-mail: eazoulay{at}bichat.inserm.fr.

Antimicrobial Agents and Chemotherapy, March 2004, p. 765-773, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.765-773.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zhanel, G. G., James, J., Derkatch, S., Laing, N., Noreddin, A. M., Hoban, D. J. (2006). Pharmacodynamic activity of garenoxacin against ciprofloxacin-resistant Streptococcus pneumoniae. J Antimicrob Chemother 58: 112-116 [Abstract] [Full Text]  
  • Poole, K. (2005). Efflux-mediated antimicrobial resistance. J Antimicrob Chemother 56: 20-51 [Abstract] [Full Text]  
  • Azoulay-Dupuis, E., Bedos, J. P., Mohler, J., Moine, P., Cherbuliez, C., Peytavin, G., Fantin, B., Kohler, T. (2005). Activity of Gemifloxacin against Quinolone-Resistant Streptococcus pneumoniae Strains In Vitro and in a Mouse Pneumonia Model. Antimicrob. Agents Chemother. 49: 1046-1054 [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»