[Susceptibility of clinically-isolated bacteria strains to respiratory quinolones and evaluation of antimicrobial agent efficacy by Monte Carlo simulation].

Abstract

Respiratory quinolones (RQs) are broad-spectrum antimicrobial agents used for the treatment of a wide variety of community-acquired and nosocomial infections. However, bacterial resistance to quinolones has been on the increase. In this study, we investigated the predicted efficacy of RQs for various strains of 9 bacterial species clinically isolated at our university hospital using the Monte Carlo simulation (MCS) method based on pharmacokinetics/pharmacodynamics modeling. In addition, the influence of the patients' renal function on the efficacy of RQs was evaluated. We surveyed antimicrobial susceptibility testing of 9 bacterial species (n = number of strains) [Streptococcus pneumoniae (n = 15), Streptococcus pyogenes (n = 14), Streptococcus agalactiae (n = 19), methicillin-susceptible Staphylococcus aureus (MSSA) (n = 24), Escherichia coli (n = 35), Haemophilus influenzae (n = 17), Klebsiella pneumoniae (n = 14), Pseudomonas aeruginosa (n = 31), and Moraxella catarrhalis (n = 11)] to 4 RQs [garenoxacin (GRNX), levofloxacin (LVFX), sitafloxacin (STFX), and moxifloxacin (MFLX)]. We found that compared with the other RQs, Gram-positive cocci was most resistant to LVFX, and that the minimum inhibitory concentration (MIC₉₀) values for S. pneumoniae, S. pyogenes, S. agalactiae, and MSSA were high (2, 16, > 16, and 8 µg/mL, respectively). In regard to Gram-negative rods, the susceptibility of E. coli to RQs was found to be decreased, with the MIC₉₀ values of GRNX, LVFX, STFX, and MFLX being > 16, 16, 1, and 16 µg/mL, respectively. MCS revealed that the target attainment rate of the area under the unbound concentration-time curve divided by the MIC₉₀ (ƒ · AUC/MIC ratio), against S. pneumoniae was 86.9-100%, but against E. coli was low (52.1-66.2%). The ƒ · AUC/MIC target attainment rate of LVFX against S. pneumoniae, S. pyogenes, and S. agalactiae tended to decrease due to increased creatinine clearance, and that of LVFX and STFX against MSSA also tended to decrease. The findings of this study suggest that the drug susceptibility distribution of each RQ varies, even within the same bacterial species, and that the expected efficacy also varies between the drugs. Moreover, the influence of the patient's renal function on the efficacy differed among the 3 renal excretory drugs (GRNX, LVFX, and STFX), thus suggesting that the efficacy also differs. In conclusion, the findings of this study show that for the administration of RQs, it is desirable to select agents in consideration of surveyed sensitivity within the population and the pharmacokinetic characteristics.