RESEARCH ARTICLE


Protection Afforded by Fluoroquinolones in Animal Models of Respiratory Infections with Bacillus anthracis, Yersinia pestis, and Francisella tularensis



Johnny W Peterson1, *, Scott T Moen2, Daniel Healy3, Jennifer E Pawlik4, Joanna Taormina5, Jason Hardcastle6, John M Thomas7, William S Lawrence8, Cindy Ponce9, Bagram M Chatuev10, Bryan T Gnade11, Sheri M Foltz12, Stacy L Agar13, Jian Sha14, Gary R Klimpel15, Michelle L Kirtley16, Tonyia Eaves-Pyles17, Ashok K Chopra18
1 Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610
2 Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610
3 James Winkle College of Pharmacy, University of Cincinnati Health Sciences Center, Cincinnati, OH 45267-0004
4 Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610
5 Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610
6 Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610
7 Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610
8 Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610
9 Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610
10 Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610
11 Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610
12 Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610
13 Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610
14 Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610
15 Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610
16 Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610
17 Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610
18 Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610


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© Peterson et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd. Galveston, Texas 77555-0610, USA; Tel: (409) 266-6917; Fax: (409) 266-6810; E-mail johnny.peterson@utmb.edu


Abstract

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.

Keywords: Anthrax, plague, tularemia, ciprofloxacin, levofloxacin, animal models.