WQ-3034 and HSR-903 are newly synthesized fluoroquinolones with potent antimicrobial activity against common gram-positive cocci. We assessed the
in vitro activity of WQ-3034 and HSR-903 against
Mycobacterium tuberculosis (MTB) and
Mycobacterium avium complex (MAC) by using levofloxacin (LVFX), ciprofloxacin (CPFX), sparfloxacin (SPFX), gatifloxacin (GFLX), and sitafloxacin (STFX) as reference drugs. First, the MICs of all of these drugs were determined by the agar dilution method with 7H11 medium. The MICs at which 50% and 90% of the test MTB strains were inhibited (MIC
50 and MIC
90, respectively) by the test quinolones were: rifampicin (RFP)-susceptible MTB, STFX (0.1, 0.2μg/mL)≤GFLX (0.1, 0.39μg/mL)≤SPFX (0.2, 0.39μg/mL)<LVFX (0.39, 1.56μg/mL)≤WQ-3O34≅HSR-903≅CPFX (0.78, 1.56μg/mL); RFP-resistant MTB, STFX≅GFLX (0.39, 1.56 μg/mL)<SPFX (1.56, 3.13μg/mL)≤WQ-3034 (1.56, 6.25μg/mL)<LVFX (3.13, 6.25μg/mL)≤HSR-903 (3.13, 25μg/mL)≅CPFX (6.25, 12.5 μg/mL). On the other hand, the MIC
90 and MIC
90 of the test quinolones for MAC isolates were: RFP-susceptible MAC, STFX≅GFLX (6.25, 6.25μg/mL)<SPFX≅HSR-903 (12.5, 12.5μg/mL)<WQ-3034≅LVFX≅CPFX (25, 25μg/mL); RFP-resistant MAC, STFX≅SPFX (1.56, 1.56μg/mL)<GFLX≅WQ-3034>HSR-903≅CPFX (3.13, 3.13μg/mL)<LVFX (6.25, 6.25μg/mL). Second, we compared the antimicrobial activity of the test drugs against the MTB 93062 strain residing in the Mono Mac 6 macrophage cell line (MM6-Mφs) and the A-549 type II alveolar cell line (A-549 cells). When the drugs were added at the blood C
max, progressive killing or inhibition of the MTB residing in MM6-Mφs and A-549 cells was observed in the order: SPFX LVFX>WQ-3034>CPFX. The efficacy of all of the quinolones against intracellular MTB was significantly lower in the A-549 cells than in the MM6-M-s. WQ-3034, HSR-903, and LVFX at their MIC caused growth inhibition of intramacrophage MTh Kurono strain in the order: WQ-3034>HSR-903>LVFX. These findings indicate that the anti-MTB and anti-MAC activity of WQ-3034 is greater than that of CPFX and comparable to that of LVFX, while the activity of HSR-903 is somewhat greater than or comparable to that of CPFX. It thus appears that an increase in the activity of a given quinolone against gram-positive cocci does not necessarily mean increased activity of that drug against MTB organisms. Third, we examined the activity of WQ-3034 and HSR-903 alone and in combination with other antimycobacterial drugs against extracellularly growing MAC. The activity of these quinolones was reduced by combination with either clarithromycin or RFP but significantly potentiated by combination with isoniazid.
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