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Antimicrobial Agents and Chemotherapy, February 2003, p. 653-657, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.653-657.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Sterilizing Activities of Fluoroquinolones against Rifampin-Tolerant Populations of Mycobacterium tuberculosis

Yanmin Hu,1 Anthony R. M. Coates,2 and Denis A. Mitchison1*

Department of Medical Microbiology, St. George's Hospital Medical School, London,1 Biotherapies Ltd., Stockport, United Kingdom2

Received 18 July 2002/ Returned for modification 15 October 2002/ Accepted 12 November 2002

The bactericidal activities of ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, and gatifloxacin were tested in three models of rifampin-tolerant Mycobacterium tuberculosis persisters. Model 1 was a 100-day-old, unshaken, anaerobically adapted culture in which serial dilutions of the quinolones were incubated for 5 days and CFU counts were then done In models 2 and 3, 100 mg of rifampin/liter was added to the 100-day culture for 5 or 7 days to produce tolerant organisms that did not grow on plates; the rifampin was then washed off, fresh medium was added to allow recovery of growth on plates, and the culture was incubated for 7 days before CFU counts. In model 2, the quinolones were added after rifampin had been washed off, whereas in model 3 the quinolones were added to the cultures containing rifampin. In models 1 and 2, ciprofloxacin had the least bactericidal activity, ofloxacin and levofloxacin had greater activities, and moxifloxacin and gatifloxacin had the greatest activities. In model 3, ofloxacin had no detectable activity whereas moxifloxacin killed about log10 0.279 CFU of the persisters per ml at concentrations attainable in lesions; isoniazid had virtually no activity. These findings predict that ofloxacin will not be found to have effective sterilizing activity in clinical studies now planned whereas moxifloxacin will be able to shorten treatment.

* Corresponding author. Mailing address: Department of Medical Microbiology, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom. Phone: 44 208 725 5704. Fax: 44 208 672 0234. E-mail: dmitchis{at}sghms.ac.uk.

Antimicrobial Agents and Chemotherapy, February 2003, p. 653-657, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.653-657.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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