A comparison of the bactericidal activity of quinolone antibiotics in a Mycobacterium fortuitum model.
New agents are urgently needed to meet the threat of multiple drug-resistant tuberculosis and to manage infection with the naturally resistant non-tuberculosis mycobacteria. Earlier fluoroquinolones have been shown to have promising in-vitro activity, although mouse infection and clinical studies suggested that they lack sufficient bactericidal activity. Methods were evaluated to measure the bactericidal activity of fluoroquinolones and to compare the new agent moxifloxacin with other fluoroquinolones with M. fortuitum as a model system. The optimum bactericidal concentrations (OBC) for the fluoroquinolones were: moxifloxacin, 0.5 mg/L; ciprofloxacin and sparfloxacin, 2 mg/L and ofloxacin, 8 mg/L. The bactericidal indices (BI) for moxifloxacin, ciprofloxacin, sparfloxacin and ofloxacin were 1.8, 0.5, 0.2 and 0.2, respectively. Similar ranking was obtained when the time taken to produce one log10 reduction in viable count was calculated. These data indicate that moxifloxacin was the most bactericidal of the fluoroquinolones tested. Such methods provide a simple in-vitro measure that correlates with in-vivo models.
Gillespie
Stephen H
SH
Morrissey
Ian
I
Royal Free & University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF and *GR Micro Ltd, 7-9 William Road, London NW1 3ER.
Everett
Dean
D
D000890:Anti-Infective Agents / Q000494:pharmacology*; D001372:Aza Compounds; D002939:Ciprofloxacin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D024841:Fluoroquinolones; D006801:Humans; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D000077266:Moxifloxacin; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy*; D019907:Mycobacterium fortuitum / Q000187:drug effects*; D015242:Ofloxacin / Q000494:pharmacology; D011804:Quinolines
D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D002939:Ciprofloxacin; D015242:Ofloxacin; C061363:sparfloxacin; D000077266:Moxifloxacin