Accession Number:

ADA443612

Title:

Effective Antimicrobial Regimens for Use in Humans for Therapy of Bacillus anthracis Infections and Postexposure Prophylaxis

Descriptive Note:

Journal article

Corporate Author:

ORDWAY RESEARCH INST ALBANY NY

Report Date:

2005-12-01

Pagination or Media Count:

10.0

Abstract:

Expanded options for treatments directed against pathogens that can be used for bioterrorism are urgently needed. Treatment regimens directed against such pathogens can be identified only by using data derived from in vitro and animal studies. It is crucial that these studies reliably predict the efficacy of proposed treatments in humans. The objective of this study was to identify a levofloxacin treatment regimen that will serve as an effective therapy for Bacillus anthracis infections and postexposure prophylaxis. An in vitro hollow-fiber infection model that replicates the pharmacokinetic profile of levofloxacin observed in humans half-life t12, 7.5 h or in animals, such as the mouse or the rhesus monkey t12, approximately 2 h, was used to evaluate a proposed indication for levofloxacin 500 mg once daily for the treatment of Bacillus anthracis infections. The results obtained with the in vitro model served as the basis for the doses and the dose schedules that were evaluated in the mouse inhalational anthrax model. The effects of levofloxacin and ciprofloxacin treatment were compared to those of no treatment untreated controls. The main outcome measure in the in vitro hollow-fiber infection model was a persistent reduction of culture density or 4 log10 reduction and prevention of the emergence of levofloxacin-resistant organisms. In the mouse inhalational anthrax model the main outcome measure was survival. The results indicated that levofloxacin given once daily with simulated human pharmacokinetics effectively sterilized Bacillus anthracis cultures. By using a simulated animal pharmacokinetic profile, a once-daily dosing regimen that provided a human-equivalent exposure failed to sterilize the cultures. Dosing regimens that partially humanized levofloxacin exposures within the constraints of animal pharmacokinetics reproduced the

Subject Categories:

  • Anatomy and Physiology
  • Microbiology
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE