WQ-3034 is a newly synthesized acidic fluoroquinolone. We assessed its in vitro activity against Mycobacterium tuberculosis and M. avium complex using levofloxacin (LVFX), ciprofloxacin (CPFX), sparfloxacin (SPFX), and KRM-1648 (KRM) as reference drugs. The MICs of these agents were determined by the agar dilution method with 7H11 medium. The MICs at which 50 and 90% of the test strains were inhibited (MIC 50 The recent epidemic of AIDS has caused a worldwide increase in intractable mycobacterial infections including multidrug-resistant tuberculosis (MDR-TB) and disseminated Mycobacterium avium complex (MAC) infections (8, 23). New quinolones are recommended for use for clinical control of MDR-TB (6), since they exhibit good bactericidal activity against Mycobacterium tuberculosis, achieve effective levels in serum, in tissue, and inside cells following oral administration, and produce few adverse effects (2, 7, 10). Quinolones including ofloxacin (OFLX), levofloxacin (LVFX), ciprofloxacin (CPFX), and sparfloxacin (SPFX) exhibited good therapeutic efficacy against experimental M. tuberculosis infection in mice (11, 13) and also exerted clinical efficacy against tuberculosis including MDR-TB when they were given in combination with other drugs including rifampin (RMP), isoniazid, pyrazinamide, ethambutol, and some aminoglycosides (2, 7).WQ-3034, a new acidic fluoroquinolone (Fig. 1), has been reported to possess a broad spectrum of action against common bacteria. This drug has much stronger activity than other fluoroquinolones, including CPFX, LVFX, SPFX, grepafloxacin, gatifloxacin, and moxifloxacin, against Antimicrob. Agents Chemother., abstr. F-164, 1997). Moreover, WQ-3034 exhibits potent therapeutic efficacy against S. pneumoniae infection induced in mice (Ohshita et al., 38th ICAAC). In the present study, the in vitro antimicrobial activities of WQ-3034 against M. tuberculosis and MAC were compared with those of LVFX, CPFX, and SPFX, which have been shown to possess potent antimycobacterial activities (9,11,13,16,17). In Japan, OFLX and LVFX (which is the L isomer of OFLX and which is twice as active as OFLX) (16, 17) have been used by preference for the clinical control of intractable tuberculosis, since they have good pharmacokinetic properties and potent antimycobacterial activities (2, 5, 10). We therefore mainly compared the activity of WQ-3034 with that of LVFX. We also used a new benzoxazinorifamycin, KRM-1648 (KRM), which has strong activity against M. tuberculosis (21), as a comparison drug.
MATERIALS AND METHODSOrganisms. M. tuberculosis (45 strains), M. avium (20 strains), and Mycobacterium intracellulare (20 strains) isolated from sputum specimens of patients with tuberculosis or MAC infections in Japan were grown in 7H9 medium. The M. tuberculosis and MAC strains were isolated in several hospitals in different districts of Japan. The M. tuberculosis strains were divided into two groups on the basis of their susceptibilities to RMP, as follows. One is RMP-susceptible MTB
