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: H Tomioka, K Sato, H Kajitani, T Akaki, S Shishido
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 44 Issue 2 Pg. 283-6 (Feb 2000) ISSN: 0066-4804 [Print] United States
• PMID: 10639351 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-Quinolones
• Aminopyridines
• Anti-Infective Agents
• Antitubercular Agents
• Fluoroquinolones
• Quinolones
• Rifamycins
• WQ 3034
• KRM 1648
• Ciprofloxacin
• Levofloxacin
• Ofloxacin
• sparfloxacin

Topics

• 4-Quinolones
• Aminopyridines (pharmacology)
• Anti-Infective Agents (pharmacology)
• Antitubercular Agents (pharmacology)
• Ciprofloxacin (pharmacology)
• Fluoroquinolones
• Humans
• Levofloxacin
• Microbial Sensitivity Tests
• Mycobacterium avium Complex (drug effects)
• Mycobacterium tuberculosis (drug effects)
• Ofloxacin (pharmacology)
• Quinolones (pharmacology)
• Rifamycins (pharmacology)