Skip Navigation


JAC Advance Access originally published online on April 27, 2006
Journal of Antimicrobial Chemotherapy 2006 58(1):112-116; doi:10.1093/jac/dkl159
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
58/1/112    most recent
dkl159v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Zhanel, G. G.
Right arrow Articles by Hoban, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhanel, G. G.
Right arrow Articles by Hoban, D. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Pharmacodynamic activity of garenoxacin against ciprofloxacin-resistant Streptococcus pneumoniae

George G. Zhanel1–,3,*, Joanne James1, Sheldon Derkatch1, Nancy Laing1,3, Ayman M. Noreddin4 and Daryl J. Hoban1,2

1 Department of Medical Microbiology, Faculty of Medicine, University of Manitoba 5th floor, Basic Medical Sciences Building, 730 William Avenue, Winnipeg, Canada R3E 0W3 2 Department of Clinical Microbiology, MS673 Health Sciences Centre 820 Sherbrook Street, Winnipeg, Canada R3A 1R9 3 Department of Medicine, MS673 Health Sciences Centre 820 Sherbrook Street, Winnipeg, Canada R3A 1R9 4 College of Pharmacy, University of Minnesota 1208 Kirby Drive, Duluth, MN 55812, USA

Received 31 January 2006; returned 13 March 2006; revised 30 March 2006; accepted 3 April 2006

*Correspondence address. Department of Microbiology, Health Sciences Centre, MS673, 820 Sherbrook Street, Winnipeg, Manitoba R3A 1R9, Canada. Tel: +1-204-787-4902; Fax: +1-204-787-4699; E-mail: ggzhanel{at}pcs.mb.ca

Background: The pharmacodynamic parameter that best correlates with bacteriological eradication for fluoroquinolones is the free (f) area under the 24 h serum concentration curve (AUC24) to MIC (fAUC24/MIC) ratio. This study assessed garenoxacin fAUC24/MIC against ciprofloxacin-resistant Streptococcus pneumoniae using an in vitro pharmacodynamic model.

Methods: A total of 14 S. pneumoniae including 1 fluoroquinolone-susceptible and 13 ciprofloxacin-resistant S. pneumoniae (ParC, efflux, ParC with efflux, and ParC and GyrA) were studied. The quinolone-resistance determining regions (QRDRs) of parC and gyrA were sequenced and efflux was assessed using a reserpine assay. S. pneumoniae with garenoxacin MICs (mg/L) [number of strains] studied were: 0.03 [1], 0.06 [2], 0.12 [2], 0.25 [2], 0.5 [3], 1 [2] and 2 [2]. The in vitro pharmacodynamic model was inoculated with 1 x 106 cfu/mL and garenoxacin was dosed once daily at 0 and 24 h to simulate fAUC24 and t1/2 obtained after standard oral doses in healthy volunteers (400 mg once daily, free AUC24 20 mg·h/L, t1/2 16 h). Sampling was performed over 48 h to assess viable growth.

Results: Garenoxacin fAUC24/MIC achieved in the model ranged from 12 to 800. Garenoxacin fAUC24/MIC 200–800 was bactericidal (≥3 log10 killing) at 6, 24 and 48 h against ciprofloxacin-resistant S. pneumoniae mutants including ParC mutants only, efflux mutants only and ParC/efflux mutants. Garenoxacin fAUC24/MIC 48–96 was bactericidal (≥3 log10 killing) at 24 and 48 h against all ciprofloxacin-resistant S. pneumoniae mutants. Garenoxacin fAUC24/MIC ≤ 24 (against ParC and GyrA mutants) resulted in a bacteriostatic effect with regrowth at 24 and 48 h.

Conclusions: Garenoxacin was bactericidal against ciprofloxacin-resistant S. pneumoniae at fAUC24/MIC ≥ 48. Garenoxacin fAUC24/MIC ≤ 24 resulted in a bacteriostatic effect with regrowth at 24 and 48 h.

Keywords: S. pneumoniae , resistance , fluoroquinolones


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.