Skip Navigation



JAC Advance Access published online on March 13, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg152
© 2003 by The British Society for Antimicrobial Chemotherapy
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
51/4/905    most recent
dkg152v1
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 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 Zelenitsky, S. A.
Right arrow Articles by Harding, G. K. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zelenitsky, S. A.
Right arrow Articles by Harding, G. K. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2003 The British Society for Antimicrobial Chemotherapy

Original article

AUC0-t/MIC is a continuous index of fluoroquinolone exposure and predictive of antibacterial response for Streptococcus pneumoniae in an in vitro infection model

Sheryl A. Zelenitsky 1*, Robert E. Ariano 1, Harris Iacovides 2, Siyao Sun 2, Godfrey K. M. Harding 3

1 Faculties of Pharmacy and Medicine, University of Manitoba; Pharmacy, St Boniface General Hospital, Winnipeg, MB, Canada
2 Faculty of Pharmacy, University of Manitoba
3 Faculty of Medicine, University of Manitoba; Infectious Diseases and Microbiology Laboratory, St Boniface General Hospital, Winnipeg, MB, Canada

* Corresponding author. E-mail: zelenits{at}ms.umanitoba.ca.

Received 27 August 2002 ; revised 26 November 2002 ; accepted 11 January 2003

Abstract

Objective: To conduct a comprehensive pharmacodynamic analysis of moxifloxacin and levofloxacin against Streptococcus pneumoniae in an in vitro infection model.

Methods: In dose escalation studies, single doses with peak concentrations equivalent to 1 x, 2 x, 4 x, 8 x, 16 x and 32 x MIC against two isolates of S. pneumoniae were studied over 24 h. Traditional pharmacodynamic indices, including peak concentration divided by MIC (peak/MIC), time of concentration above MIC (T > MIC) and AUC24/MIC, were estimated for all regimens. As a continuous index of fluoroquinolone exposure, AUC0-t/MIC was also calculated, as AUC from time 0 to 1, 2 and 6 h divided by MIC. Correlations between pharmacodynamic indices and antibacterial effects were examined using linear and non-linear methods. In validation experiments, the pharmacodynamic model was used to predict bacterial kill curves, produced by simulated clinical doses of moxifloxacin and levofloxacin against two other S. pneumoniae isolates.

Results: Peak/MIC was most predictive of early bacterial kill, whereas T > MIC was significantly associated with final bacterial counts at 24 h. Antibacterial effects were bacteriostatic when T > MIC was 48% and bactericidal when values exceeded 55%. AUC0-t/MIC was strongly associated with bacterial kill throughout the dosing interval. Bactericidal activity and bacterial eradication were associated with AUC0-t/MICs of 28 and 135, respectively. AUC0-t/MIC was also highly predictive of bacterial kill curves produced by simulated clinical doses of moxifloxacin and levofloxacin (precision 0.36 log10 cfu/mL, bias 0.02 log10 cfu/mL).

Conclusion: This study demonstrated the novel application of AUC0-t/MIC as a continuous index of antibiotic activity, and provided extensive characterization of fluoroquinolone pharmacodynamics against S. pneumoniae.

Keywords: moxifloxacin, levofloxacin, pharmacodynamics, pneumococcus
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.