Journal des maladies infectieuses et de la thérapie

Abstrait

Efficacy Testing of Orally Administered Antibiotics against an Inhalational Bacillus anthracis Infection in BALB/C Mice

Graham J Hatch, Simon R Bate, Anthony Crook, Nicola Jones, Simon G Funnell and Julia Vipond

Anthrax is a potentially fatal disease in man, and events of the last decade have highlighted the possibility for Bacillus anthracis to be used as a biological weapon through deliberate release. Whilst outbreaks of anthrax occur in several countries, there are only a few areas in which outbreaks of inhalational anthrax occur, so it is not possible to test therapies using conventional clinical trials. To overcome these problems, the FDA published the ‘Animal Rule’ in 2002; a rule designed to permit licensure of drugs and biologics intended to reduce or prevent serious conditions caused by exposure to biological and other agents. Due to limited proven post-exposure prophylaxis after inhalational exposure for use in humans, it is essential to have a robust animal model of disease. In a series of three studies conducted in BALB/c mice, the efficacy of postexposure, orally administered antibiotics in preventing disease following inhalational exposure to B. anthracis was evaluated. Mice treated with either azithromycin or clarithromycin displayed a near identical disease progression to the control, untreated mice; in contrast, those treated with levofloxacin, amoxicillin and co-amoxiclav were generally protected with survival of 97%, 95% and 79%, respectively. The details of the assessments and future direction of these studies are presented.