IN-VITRO ACTIVITIES OF LEVOFLOXACIN USED ALONE AND IN COMBINATION WITH FIRST-LINE AND 2ND-LINE ANTITUBERCULOUS DRUGS AGAINST MYCOBACTERIUM-TUBERCULOSIS

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 commerci ally available mixture containing equal amounts of DL-isomers (ofloxac in) against the Mycobacterium tuberculosis complex (type strain H37Rv, a panel of drug-susceptible and -resistant clinical isolates Includin g multidrug-resistant isolates of M. tuberculosis, as well as M. afric anum, M. bovis, and M. bovis BCG). Levofloxacin MICs (range, 0.50 to 0 .75 mu g/ml) were about 1 dilution lower than those of ofloxacin (MIC range, 0.75 to 1.00 mu g/ml) and 5 to 6 dilutions lower than those of the D isomer (MIC range, 32 to 60 mu g/ml). The MICs of levofloxacin, ofloxacin, and D-ofloxacin at which 90% of the strains are inhibited w ere 0.50, 1.00, and 6 1 mu g/ml, respectively, The multidrug-resistant M. tuberculosis strains resistant to first-line drugs were as suscept ible to quinolones as the wild-type drug-susceptible isolates, Levoflo xacin at 0.5 mu g/ml showed bactericidal activity comparable to the ac tivities of 1.0 mu g of ofloxacin per ml and 64 mu g of ofloxacin per ml, with MBCs within the range of 0.5 to 2.0 mu g/ml, compared with MB Cs of 0.75 to 4.0 mu g of ofloxacin per ml for M. tuberculosis, M. afr icanum, M. bovis, and M. bovis BCG, Combination testing of sub-MICs of levofloxacin with other first-line (isoniazid, rifampin, and ethambut ol) and second-line (amikacin and clofazimine) antituberculous drugs w as evaluated with various two-, three-, and four-drug combinations; en hanced drug activity was observed in 8 of 25, 12 of 20, and 8 of 15 te sts, respectively; indicating that levofloxacin acts in synergy with o ther antituberculous drugs.