Mutant selection window of four quinolone antibiotics against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis

Abstract

Community-acquired pneumonia and otitis media are caused by several bacterial species, including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. For the treatment of these diseases, various quinolones are frequently used. We determined the mutant prevention concentration (MPC) of four quinolones, levofloxacin, sitafloxacin, tosufloxacin, and garenoxacin, using 92 clinical isolates and evaluated each mutant selection window (MSW). Furthermore, the DNA sequence of the quinolone resistance-determining region (QRDR) for the resistant mutant selected based on the MSW was determined. The MIC₉₀ and MPC₉₀ of levofloxacin were 0.781 μg/mL and 6.250 μg/mL for S. pneumoniae and 0.049 μg/mL and 1.563 μg/mL for M. catarrhalis and were higher than those for the other three quinolones. In addition, 5 strains of 30 S. pneumoniae (16.7%) selected based on the MSW of levofloxacin acquired resistance to only levofloxacin. In these 5 strains, a mutation of gyrA and/or parC was detected. In this study, no resistant mutant was selected in the MSW of any of the other three quinolones. On the other hand, clinical isolates of H. influenzae showed no resistance by all quinolone exposure. Finally, The MIC value and the mutation status in the QRDR did not change after 14 passages in antibiotic-free medium. In conclusion, our findings suggest that the increased use of levofloxacin may contribute to the increased quinolone-resistance of S. pneumoniae and M. catarrhalis.

Keywords: Haemophilus influenzae; Moraxella catarrhalis; Mutant selection window; Quinolone resistance-determining region; Streptococcus pneumoniae.