Determination of Antibiotic Efficacy Against Bacillus Anthracis in a Mouse Aerosol Challenge Model

摘要

An anthrax-spore aerosol infection mouse model was developed as a first test of in vivo efficacy of antibiotics identified as active against Bacillus anthracis. Whole-body, LD50 aerosol challenge doses in a range of 1.9 x10(3) to 3.4 x 10(4) with spores of the fully virulent Ames strain were established for three inbred and one outbred mouse strain (A/J, BALB/c, C57BL and Swiss Webster). The BALB/c strain was further developed as a model for antibiotic efficacy. Time-course microbiological examination of tissue burdens in mice after challenge showed that spores could remain dormant in the lungs while vegetative cells disseminated to the mediastinal lymph nodes and then to the spleen accompanied with bacteremia. For antibiotic efficacy studies, BALB/c mice were challenged with 50-100 LD50 of spores followed by intraperitoneal (i.p.) injection of either ciprofloxacin 30 mg/kg (q12h), or doxycycline 40 mg/kg (q6h). A control group was treated with PBS q6h. Treatment was begun 24 h after challenge in groups of 10 mice for 14 or 21 days. The PBS-treated control mice all succumbed (10/10) to inhalation anthrax infection within 72 h. Sixty- day survival rates for ciprofloxacin and doxycycline-treated groups were 8/10, 9/10 for 14-day treatment and 10/10, 7/10 for 21-day treatment. Delayed treatment with ciprofloxacin initiated 36- and 48-h postexposure resulted in 80% survival and was statistically no different than early postexposure (24 h) treatment. This mouse model correlates closely with clinical observations of inhalational anthrax in humans and with earlier antibiotic studies in the non- human primate inhalational-anthrax model.