title: In vitro activities of levofloxacin used alone and in combination with first- and second-line antituberculous drugs against Mycobacterium tuberculosis.
abstract: By using the radiometric BACTEC 460-TB methodology, the inhibitory and bactericidal activity of the optically active L-isomer of ofloxacin (levofloxacin) was compared with those of the D-isomer and the commercially available mixture containing equal amounts of DL-isomers (ofloxacin) against the Mycobacterium tuberculosis complex (type strain H37Rv, a panel of drug-susceptible and -resistant clinical isolates including multidrug-resistant isolates of M. tuberculosis, as well as M. africanum, M. bovis, and M. bovis BCG). Levofloxacin MICs (range 0.50 to 0.75 microgram/ml) were about 1 dilution lower than those of ofloxacin (MIC range, 0.75 to 1.00 microgram/ml) and 5 to 6 dilutions lower than those of the D-isomer (MIC range, 32 to 60 micrograms/ml). The MICs of levofloxacin, ofloxacin, and D-ofloxacin at which 90% of the strains are inhibited were 0.50, 1.00, and 64 micrograms/ml, respectively. The multidrug-resistant M. tuberculosis strains resistant to first-line drugs were as susceptible to quinolones as the wild-type drug-susceptible isolates. Levofloxacin at 0.5 microgram/ml showed bactericidal activity comparable to the activities of 1.0 microgram of ofloxacin per ml and 64 micrograms of D-ofloxacin per ml, with MBCs within the range of 0.5 to 2.0 micrograms/ml, compared with MBCs of 0.75 to 4.0 micrograms of ofloxacin per ml for M. tuberculosis, M. africanum, M. bovis BCG. Combination testing of sub-MICs of levolofoxacin with other first-line (isoniazid, rifampin, and ethambutol) and second-line (amikacin and clofazimine) antituberculous drugs was evaluated with various two-, three-, and four-drug combinations; enhanced drug activity was observed in 8 of 25, 12 of 20, and 8 of 15 tests, respectively, indicating that levofloxacin acts in synergy with other antituberculous drugs.
authors.affiliation: Unité de la Tuberculose et des Mycobactéries, Institut Pasteur, Guadeloupe, French West Indies.
authors.forename: N
authors.initials: N
authors.lastname: Rastogi
authors.forename: K S
authors.initials: KS
authors.lastname: Goh
authors.forename: A
authors.initials: A
authors.lastname: Bryskier
authors.forename: A
authors.initials: A
authors.lastname: Devallois
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology; D000995:Antitubercular Agents / Q000494:pharmacology*; D004347:Drug Interactions; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D009163:Mycobacterium bovis / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D015242:Ofloxacin / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D000890:Anti-Infective Agents; D000995:Antitubercular Agents; D064704:Levofloxacin; D015242:Ofloxacin