Smith H J, Noreddin A M, Siemens C G, Schurek K N, Greisman J, Hoban C J, Hoban D J, Zhanel G G
Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Canada.
Antimicrob Agents Chemother. 2004 Sep;48(9):3630-5. doi: 10.1128/AAC.48.9.3630-3635.2004.
We determined fluoroquinolone microbiological resistance breakpoints for Streptococcus pneumoniae by using genetic instead of pharmacokinetic-pharmacodynamic parameters. The proposed microbiological breakpoints define resistance as the MIC at which >50% of the isolates carry quinolone resistance-determining region mutations and/or, if data are available, when Monte Carlo simulations demonstrate a <90% chance of bacteriological eradication. The proposed microbiological resistant breakpoints are as follows (in micrograms per milliliter): gatifloxacin, >0.25; gemifloxacin, >0.03; levofloxacin, >1; and moxifloxacin, >0.12. Monte Carlo simulations of the once daily 400-mg doses of gatifloxacin and 750-mg doses levofloxacin demonstrated a high level of target attainment (free-drug area under the concentration-time curve from 0 to 24 h/MIC ratio of 30) by using these new genetically derived breakpoints.
我们通过使用遗传学参数而非药代动力学-药效学参数来确定肺炎链球菌对氟喹诺酮类药物的微生物学耐药性断点。提议的微生物学断点将耐药性定义为：当超过50%的分离株携带喹诺酮耐药决定区突变时的最低抑菌浓度（MIC），和/或（如果有数据）当蒙特卡洛模拟显示细菌清除几率小于90%时的MIC。提议的微生物学耐药断点如下（以微克/毫升计）：加替沙星，>0.25；吉米沙星，>0.03；左氧氟沙星，>1；莫西沙星，>0.12。使用这些新的基于遗传学得出的断点，对每日一次400毫克剂量的加替沙星和750毫克剂量的左氧氟沙星进行蒙特卡洛模拟，结果显示达到目标的水平较高（0至24小时浓度-时间曲线下的游离药物面积/MIC比值为30）。
