Successful treatment of
inhalation anthrax,
pneumonic plague and
tularemia can be achieved with
fluoroquinolone antibiotics, such as
ciprofloxacin and
levofloxacin, and initiation of treatment is most effective when administered as soon as possible following exposure. Bacillus anthracis Ames, Yersinia pestis CO92, and Francisella tularensis SCHU S4 have equivalent susceptibility in vitro to
ciprofloxacin and
levofloxacin (minimal inhibitory concentration is 0.03 μg/ml); however, limited information is available regarding in vivo susceptibility of these infectious agents to the
fluoroquinolone antibiotics in small animal models. Mice, guinea pig, and rabbit models have been developed to evaluate the protective efficacy of
antibiotic therapy against these life-threatening
infections. Our results indicated that doses of
ciprofloxacin and
levofloxacin required to protect mice against
inhalation anthrax were approximately 18-fold higher than the doses of
levofloxacin required to protect against
pneumonic plague and
tularemia. Further, the critical period following
aerosol exposure of mice to either B. anthracis spores or Y. pestis was 24 h, while mice challenged with F. tularensis could be effectively protected when treatment was delayed for as long as 72 h postchallenge. In addition, it was apparent that prolonged
antibiotic treatment was important in the effective treatment of
inhalation anthrax in mice, but short-term treatment of mice with
pneumonic plague or
tularemia infections were usually successful. These results provide effective
antibiotic dosages in mice, guinea pigs, and rabbits and lay the foundation for the development and evaluation of combinational treatment modalities.