title: Moxifloxacin and gatifloxacin in an acid model of persistent Mycobacterium tuberculosis.
abstract: Studies in the mouse and in humans suggest that use of moxifloxacin and gatifloxacin may shorten the duration of treatment of pulmonary tuberculosis. We describe here the in vitro findings with gatifloxacin and moxifloxacin in regimens similar to those that might be used in the treatment of tuberculosis. The bactericidal activities of moxifloxacin and gatifloxacin were measured alone and in different combinations with isoniazid, rifampicin and pyrazinamide against a 30-day, stationary phase culture, at a pH of 5.9. There was a rapid, irregular fall in colony counts during the first 4 days followed by a slower consistent kill during days 4-21 with a mean kill of -0.36 (SD=2.74) and -0.106 (SD=0.011) log(10)CFU/ml/day, respectively. The 4-21-day kill is considered the best assessment of bactericidal activity against persisting bacilli that prolong treatment. The substitution of either of the quinolones for isoniazid in the control regimen of rifampicin, pyrazinamide and isoniazid did not increase bactericidal activity with log CFU of 5.00 and 4.88, but did result in increased bactericidal action with the log CFU of 4.11 and 4.10 for moxifloxacin and gatifloxacin respectively. Moxifloxacin and gatifloxacin had closely similar activities in all drug combinations. Adding moxifloxacin or gatifloxacin to the control regimen resulted in a significant increase in bactericidal action, considered sufficient to reduce the treatment duration.
authors.affiliation: Tuberculosis Research Center (ICMR), Chennai, India.
authors.forename: G
authors.initials: G
authors.lastname: Kubendiran
authors.forename: C N
authors.initials: CN
authors.lastname: Paramasivan
authors.forename: S
authors.initials: S
authors.lastname: Sulochana
authors.forename: D A
authors.initials: DA
authors.lastname: Mitchison
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D001372:Aza Compounds / Q000494:pharmacology*; D015169:Colony Count, Microbial; D004357:Drug Synergism; D024841:Fluoroquinolones / Q000494:pharmacology*; D000077734:Gatifloxacin; D006863:Hydrogen-Ion Concentration; D007538:Isoniazid / Q000494:pharmacology; D000077266:Moxifloxacin; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D011718:Pyrazinamide / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000995:Antitubercular Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D011718:Pyrazinamide; D000077734:Gatifloxacin; D000077266:Moxifloxacin; D007538:Isoniazid; D012293:Rifampin