Vol.69 No.6 November 2021

Antimicrobial susceptibilities of bacterial strains of the Streptococcus anginosus group and Streptococcus mitis group, and determination of the mutant prevention concentration and mutant selection window of lascufloxacin for oral streptococci

Akihiro Kaneko, Nobuhito Mizusawa, Ryuta Osaka and Daisuke Watanabe

Department of Oral Surgery, Ikegami General Hospital, 6-1-19 Ikegami, Ohta-ku, Tokyo, Japan

Abstract

Strains of the Streptococcus anginosus group (SAG) and Streptococcus mitis group (SMG) have been detected in the bronchoalveolar lavage fluid of pneumonia patients, however, the microbial susceptibilities of these bacterial species have not yet been sufficiently studied. In addition, reduction in the bacterial susceptibilities of these bacteria to levofloxacin (LVFX) has been reported. Therefore, the antimicrobial susceptibilities of strains of SAG and SMG were examined. Furthermore, the mutant prevention concentrations (MPC) and mutant selection windows (MSW) of lascufloxacin (LSFX), LVFX and garenoxacin (GRNX) were also determined.
The subjects were 10 strains each of SAG (S. anginosus, S. constellatus and S. intermedius) and SMG (S. mitis, S. oralis and S. sanguinis) isolated from patients with odontogenic infections between 2018 and 2019. The susceptibilities of these oral streptococci to eight antimicrobial agents (LSFX, LVFX, GRNX, moxifloxacin, tazobactam/piperacillin, ceftriaxone, meropenem and azithromycin) were examined.
The resistance rates to AZM of the SAG were in the range of 20-40% and those of the SMG were in the range of 40-60%. Among the strains, the MIC₉₀ for S. sanguinis was the highest (16 μg/mL). The MPC₉₀ value of LSFX was the lowest for S. anginosus, S. constellatus, S. intermedius and S. sanguinis, and the values of both LSFX and GRNX were the lowest for S. mitis and S. oralis. The MSW of LVFX tended to be wide, while those of LSFX and GRNX were comparable. The MPC₉₀/MIC₉₀ ratio of LVFX was 8 for both S. intermedius and S. sanguinis, whereas the ratios of LSFX and GRNX were 2-4 for all the strains.
The AUC/MIC and C_max/MIC were calculated using previously reported steady-state plasma concentrations. The AUC/MIC of LSFX, LVFX and GRNX for the SAG were 433.3, 99.3 and 1,848.3, respectively, and the corresponding values for the SMG were 216.7-433.3, 49.7-99.3 and 1,848.3, respectively. The C_max/MIC of LSFX, LVFX and GRNX for the SAG were 33.3, 12.6 and 184.3, respectively, and the corresponding values for the SMG were 16.6-33.3, 6.3-12.6 and 184.3, respectively. These data exceeded AUC/MIC=30 and C_max/MIC=5, respectively, which are considered as the target values. However, it has been reported that the LSFX concentrations in the epithelial lining fluid and alveolar macrophages after oral administration were higher than the plasma concentrations, 10 times higher than the MPC₉₀ values for SAG and SMG throughout a 24-hour period.

Key word

oral streptococci, antimicrobial susceptibility, lascufloxacin, mutant prevention concentration, mutant selection window

Received

August 30, 2021

Accepted

September 24, 2021

Jpn. J. Chemother. 69 (6): 417-424, 2021