Mutant prevention concentrations of garenoxacin against Streptococcus pneumoniae isolates from otorhinolaryngological infections

Abstract

Objective In recent years, the appearance of drug-resistant strains of Streptococcus pneumoniae has been attracting close attention. When dealing with cases of severe infection with S. pneumoniae, it is now essential to review drug selection and the optimum dosing method/dose level to achieve satisfactory responses and prevent the appearance of drug-resistant strains. Garenoxacin (GRNX), a respiratory quinolone, has been shown to have excellent activity against S. pneumoniae. The present study was undertaken to examine the possibility of the appearance of S. pneumoniae strains having resistance to GRNX by analysing MIC and MPC. Methods The study involved analysis and comparison of the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of GRNX, levofloxacin (LVFX), and moxifloxacin (MFLX) against 78 strains of S. pneumoniae (45 PSSP strains, 26 PISP strains, and 7 PRSP strains) isolated in January to June 2007 from patients with otorhinolaryngological infections at nationwide medical facilities. Results MIC 90 and MPC 90 against the 78 strains of S. pneumoniae were lower with GRNX (0.06 and 0.12 μg/mL, respectively) than with LVFX and MFLX. MPC/MIC ratio for GRNX ranged from 1 to 4 and was 2 or less for 77 strains (99%), lower than the same ratio for LVFX and MFLX. Conclusion GRNX exerted antibacterial activity higher than that of the other quinolone antibacterial agents tested. GRNX had a narrow MSW (mutant selection window) and its tissue drug level/MPC 90 was high enough to achieve complete killing of the bacterium. Taken together, these results suggest that treatment with GRNX (400 mg/day) is expected to exert excellent clinical efficacy against S. pneumoniae infections in the field of otorhinolaryngology and that it is also useful in preventing development of resistance of S. pneumoniae to quinolone antibacterial agents.