Zinner Stephen H, Vostrov Sergey N, Alferova Irene V, Lubenko Irene Yu, Portnoy Yury A, Firsov Alexander A
Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, MA, USA.
Int J Antimicrob Agents. 2004 Aug;24(2):173-7. doi: 10.1016/j.ijantimicag.2004.02.026.
The killing kinetics of Escherichia coli and Pseudomonas aeruginosa were compared when exposed to ABT492 and ciprofloxacin. E. coli ATCC 25922 and a clinical isolate of P. aeruginosa 4226 were exposed to ABT492 (single dose) and ciprofloxacin (two 12 h doses) at the ratios of area under the curve (AUC) to MIC varying from 60 to 480 h and at clinically achievable AUC/MIC ratios of ABT492 (1,740 and 140 h, respectively) and ciprofloxacin (2,200 and 120 h, respectively) that correspond to a 400 mg dose of ABT492 and two 500 mg doses of ciprofloxacin. In addition, a double dose of ABT492 (800 mg; AUC/MIC 280 h) and two 12 h doses of ABT492 (2 x 400 mg) were used with P. aeruginosa. Maximal reductions in the starting inoculum of E. coli and P. aeruginosa were greater with ABT492 than with ciprofloxacin at a given AUC/MIC ratio (60-480 h), whereas the times to regrowth were shorter with ABT492. A specific AUC/MIC relationship of the antimicrobial effect was inherent in each quinolone-pathogen pair. With both E. coli and P. aeruginosa, AUC/MIC plots of the area between the control growth and the time-kill curves (I(E)) were steeper for ciprofloxacin than ABT492 and they were species-independent. The effect of ABT492 on E. coli at the clinically achievable AUC/MIC ratio (1740h) was more pronounced than the respective AUC/MIC of ciprofloxacin (2,200 h). With P. aeruginosa, a 140 h AUC/MIC of ABT492 (400 mg as a single dose) provided 1.8-fold less effect than a 120 h AUC/MIC of ciprofloxacin (2 x 500 mg). However, two 12 h doses of ABT492 (AUC/MIC 2 x 140 h) but not a double single dose (800 mg) were more efficient than ciprofloxacin. These findings predict comparable efficacies of clinically achievable AUC/MICs of ABT492 and ciprofloxacin against E. coli (q.d. versus b.i.d. quinolone dosing) and P. aeruginosa at b.i.d. but not at q.d. ABT492.
比较了大肠杆菌和铜绿假单胞菌暴露于ABT492和环丙沙星时的杀菌动力学。将大肠杆菌ATCC 25922和铜绿假单胞菌临床分离株4226分别暴露于ABT492（单剂量）和环丙沙星（两个12小时剂量），曲线下面积（AUC）与最低抑菌浓度（MIC）的比值范围为60至480小时，以及ABT492（分别为1740和140小时）和环丙沙星（分别为2200和120小时）在临床上可达到的AUC/MIC比值，这分别对应于400mg剂量的ABT492和两个500mg剂量的环丙沙星。此外，对铜绿假单胞菌使用了双倍剂量的ABT492（800mg；AUC/MIC 280小时）和两个12小时剂量的ABT492（2×400mg）。在给定的AUC/MIC比值（60 - 480小时）下，ABT492使大肠杆菌和铜绿假单胞菌初始接种量的最大减少幅度大于环丙沙星，而ABT492使细菌再生长的时间更短。每种喹诺酮 - 病原体对中抗菌作用都存在特定的AUC/MIC关系。对于大肠杆菌和铜绿假单胞菌，环丙沙星的对照生长与时间 - 杀菌曲线之间区域（I(E)）的AUC/MIC图比ABT492更陡峭，且与菌种无关。在临床上可达到的AUC/MIC比值（1740小时）下，ABT492对大肠杆菌的作用比环丙沙星相应的AUC/MIC（2200小时）更显著。对于铜绿假单胞菌，ABT492的140小时AUC/MIC（单剂量400mg）的效果比环丙沙星的120小时AUC/MIC（2×500mg）低1.8倍。然而，两个12小时剂量（AUC/MIC 2×140小时）的ABT492而非双倍单剂量（800mg）比环丙沙星更有效。这些发现预测了临床上可达到的ABT492和环丙沙星的AUC/MIC对大肠杆菌（喹诺酮每日一次给药与每日两次给药相比）以及对铜绿假单胞菌每日两次给药时具有相当的疗效，但对ABT492每日一次给药则不然。
