Efficacy of Oritavancin in a Murine Model of Bacillus anthracis Spore Inhalation Anthrax
ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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The inhaled form of Bacillus anthracis infection may be fatal to humans. The current standard of care for inhalational anthrax postexposure prophylaxis is ciprofloxacin therapy twice daily for 60 days. The potent in vitro activity of oritavancin, a semisynthetic lipoglycopeptide, against B. anthracis MIC against Ames strain, 0.015 microgml prompted us to test its efficacy in a mouse aerosol-anthrax model. In postexposure prophylaxis dose-ranging studies, a single intravenous i.v. dose of oritavancin of 5, 15, or 50 mgkg 24 h after a challenge with 50 to 75 times the median lethal dose of Ames strain spores provided 40, 70, and 100 proportional survival, respectively, at 30 days postchallenge. Untreated animals died within 4 days of challenge, whereas 90 of control animals receiving ciprofloxacin at 30 mgkg intraperitoneally twice daily for 14 days starting 24 h after challenge survived. Oritavancin demonstrated significant activity post symptom development a single i.v. dose of 50 mgkg administered 42 h after challenge provided 56 proportional survival at 30 days. In a preexposure prophylaxis study, a single i.v. oritavancin dose of 50 mgkg administered 1, 7, 14, or 28 days before lethal challenge protected 90, 100, 100, and 20 of mice at 30 days mice treated with ciprofloxacin 24 h or 24 and 12 h before challenge all died within 5 days. Efficacy in pre- and postexposure models of inhalation anthrax, together with a demonstrated low propensity to engender resistance, promotes further study of oritavancin pharmacokinetics and efficacy in nonhuman primate models.
- Medicine and Medical Research