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Antimicrobial Agents and Chemotherapy, February 2000, p. 283-286, Vol. 44, No. 2
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Comparative Antimicrobial Activities of the Newly Synthesized Quinolone WQ-3034, Levofloxacin, Sparfloxacin, and Ciprofloxacin against Mycobacterium tuberculosis and Mycobacterium avium Complex

Haruaki Tomioka,1,* Katsumasa Sato,1 Hiroko Kajitani,1 Tatsuya Akaki,1,2 and Shinji Shishido3

Department of Microbiology and Immunology1 and Department of Dermatology,2 Shimane Medical University, Izumo, Shimane 693-8501, and National Sanatorium Matsue Hospital, Matsue, Shimane 690-8556,3 Japan

Received 8 March 1999/Returned for modification 7 June 1999/Accepted 10 November 1999

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 (MIC50s, and MIC90s, respectively) for the test quinolones for rifampin (RMP)-susceptible M. tuberculosis strains were in the order SPFX < LVFX less-or-equivalent  WQ-3034 less-or-equivalent  CPFX, while those for RMP-resistant M. tuberculosis strains were in the order SPFX less-or-equivalent  WQ-3034 less-or-equivalent  LVFX < CPFX. 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 MIC50s and MIC90s of the test drugs for M. avium were in the order KRM < SPFX < CPFX less-or-equivalent  WQ-3034 less-or-equivalent  LVFX, while those for M. intracellulare were in the order KRM < SPFX < WQ-3034 ≒ LVFX less-or-equivalent  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-Mphi s) 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-Mphi s 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-Mphi s. 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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Shimane Medical University, Izumo, Shimane 693-8501, Japan. Phone: 81 (853) 20-2146. Fax: 81 (853) 20-2145. E-mail: tomioka{at}shimane-med.ac.jp.

Antimicrobial Agents and Chemotherapy, February 2000, p. 283-286, Vol. 44, No. 2
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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