title: Comparative antimicrobial activities of the newly synthesized quinolone WQ-3034, levofloxacin, sparfloxacin, and ciprofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex.
abstract: 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)s, and MIC(90)s, respectively) for the test quinolones for rifampin (RMP)-susceptible M. tuberculosis strains were in the order SPFX < LVFX </= WQ-3034 </= CPFX, while those for RMP-resistant M. tuberculosis strains were in the order SPFX </= WQ-3034 </= LVFX < CPFX. The MICs of KRM for RMP-susceptible M. tuberculosis were much lower than those of the test quinolones, while the MIC(90) 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 </= WQ-3034 </= LVFX, while those for M. intracellulare were in the order KRM < SPFX < WQ-3034 LVFX </= CPFX. Next, we compared the antimicrobial activities of the test drugs against M. tuberculosis organisms residing in cells of the Mono Mac 6 macrophage (Mphi)-like cell line (MM6-Mphis) and of the A-549 type II alveolar cell line (A-549 cells). When drugs were added at the concentration that achieves the maximum concentration in blood, progressive killing or inhibition of the M. tuberculosis organisms residing in MM6-Mphis and A-549 cells was observed in the order KRM > SPFX >/= LVFX > WQ-3034 > CPFX. The efficacies of all quinolones against intracellular M. tuberculosis organisms were significantly lower in A-549 cells than in MM6-Mphis. WQ-3034 at the MIC caused more marked growth inhibition of intramacrophage M. tuberculosis than did LVFX. These findings indicate that the in vitro anti-M. tuberculosis activity of WQ-3034 is greater than that of CPFX and is comparable to that of LVFX.
authors.affiliation: Department of Microbiology and Immunology, Shimane Medical University, Izumo, Shimane 693-8501, Japan. tomioka@shimane-med.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Tomioka
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Kajitani
authors.forename: T
authors.initials: T
authors.lastname: Akaki
authors.forename: S
authors.initials: S
authors.lastname: Shishido
mesh_terms: D042462:4-Quinolones; D000631:Aminopyridines / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D024841:Fluoroquinolones; D006801:Humans; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D015269:Mycobacterium avium Complex / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D015242:Ofloxacin / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D012294:Rifamycins / Q000494:pharmacology
chemical_list: D042462:4-Quinolones; D000631:Aminopyridines; D000890:Anti-Infective Agents; D000995:Antitubercular Agents; D024841:Fluoroquinolones; D015363:Quinolones; D012294:Rifamycins; C405494:WQ 3034; C068980:KRM 1648; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin; C061363:sparfloxacin