2020 Volume 73 Issue 1 Pages 9-17
Antibacterial activities of garenoxacin (GRNX), levofloxacin (LVFX) and lascufloxacin (LSFX) against Streptococcus pneumoniae isolated from respiratory tract infection between 2016 and 2017 were measured. Based on pharmacokinetics–pharmacodynamics theory, we investigated the predicted efficacy and resistant selectivity of oral quinolones using the Monte Carlo simulation method. Mutant prevention concentration (MPC), which is the minimum concentration restricting the selection of resistance was measured.
MIC90 of GRNX against 28 strains of S. pneumoniae was 0.0625 μg/mL, being the lowest among quinolones tested, followed by 0.125 μg/mL of LSFX, and 1 μg/mL of LVFX.
The probability of target attainment at free-drug area under the curve (fAUC, f: ratio of protein-unbound)/MIC ratio (fAUC/MIC)=30 was calculated, and was assessed as the efficacy. The probabilities of GRNX, LSFX and LVFX were 100, 76.9, and 62.8%, respectively. At fCmax/ MIC=5, considered target value of resistance prevention, GRNX, LVFX and LSFX showed a probability of 100, 60.4, and 0.31%, respectively.
MPC90 of GRNX, LSFX and LVFX were 0.25 μg/mL, 2 μg/mL and 4 μg/mL, respectively, and GRNX showed the lowest MPC90 among quinolones tested. Mutant selection window (MSW) of GRNX, LSFX and LVFX were 0.19 μg/mL, 1.9 μg/mL and 3.0 μg/mL, respectively. GRNX had a narrower MSW than LSFX and LVFX.
The findings of this study suggest that the efficacy and resistant selectivity differ among oral quinolones, and GRNX is useful in terms of efficacy and resistant prevention.
