Comparative antimicrobial activities of the newly synthesized quinolone WQ-3034, levofloxacin, sparfloxacin, and ciproffoxacin against Mycobacterium tuberculosis and mycobacterium avium complex

WQ-3034 is a newly synthesized acidic fluoroquinolone. We assessed its in v itro activity against Mycobacterium tuberculosis and M. avium complex using levofloxacin (LVFX), ciprofloxacin (CPFX), sparfloxacin (SPFX), and KRM-16 48 (KRM) as reference drugs. The MICs of these agents were determined by th e agar dilution method with 7H11 medium. The MICs at which 50 and 90% of th e test strains were inhibited (MIC(50)s, and MIC(90)s, respectively) for th e test quinolones for rifampin (RMP)-susceptible M. tuberculosis strains we re in the order SPFX < LVFX less than or equal to WQ-3034 less than or equa l to CPFX, while those for RMP-resistant M. tuberculosis strains were in th e order SPFX less than or equal to WQ-3034 less than or equal to LVFX < CPF X, The MICs of KRM for RMP-susceptible M. tuberculosis were much lower than those of the test quinolones, while the MIC90 of KRM for RMP-resistant M. tuberculosis strains was higher than those of the quinolones. The MIC(50)s and MIC(90)s of the test drugs for M. avium were in the order KRM < SPFX < CPFX less than or equal to WQ-3034 less than or equal to LVFX, while those for M. intracellulare were in the order KRM < SPFX < WQ-3034 is approximate ly equal to LVFX less than or equal to CPFX. Next, we compared the antimicr obial activities of the test drugs against M. tuberculosis organisms residi ng in cells of the Mono Mac 6 macrophage (M phi)-like cell line (MM6-M phi s) and of the A-549 type II alveolar cell line (A-549 cells), When drugs we re added at the concentration that achieves the maximum concentration in bl ood, progressive killing or inhibition of the M. tuberculosis organisms res iding in MM6-M phi s and A-549 cells was observed in the order KRM > SPFX g reater than or equal to LVFX > WQ-3034 > CPFX. The efficacies of all quinol ones against intracellular M. tuberculosis organisms were significantly Low er in A-549 cells than in MM6-M phi s. WQ-3034 at the MIC caused more marke d growth inhibition of intramacrophage M. tuberculosis than did LVFX. These findings indicate that the in vitro anti-M. tuberculosis activity of WQ-30 34 is greater than that of CPFX and is comparable to that of LVFX.