Protection Afforded by Fluoroquinolones in Animal Models of Respiratory Infections with Bacillus anthracis, Yersinia pestis, and Francisella tularensis.
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.
Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610.
Johnny W
JW
Peterson
Scott T
ST
Moen
Daniel
D
Healy
Jennifer E
JE
Pawlik
Joanna
J
Taormina
Jason
J
Hardcastle
John M
JM
Thomas
William S
WS
Lawrence
Cindy
C
Ponce
Bagram M
BM
Chatuev
Bryan T
BT
Gnade
Sheri M
SM
Foltz
Stacy L
SL
Agar
Jian
J
Sha
Gary R
GR
Klimpel
Michelle L
ML
Kirtley
Tonyia
T
Eaves-Pyles
Ashok K
AK
Chopra