Karlowsky J A, Zhanel G G, Davidson R J, Hoban D J
Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Antimicrob Agents Chemother. 1994 May;38(5):1165-8. doi: 10.1128/AAC.38.5.1165.
A novel, in vitro, pharmacodynamic comparison of single and divided daily dosing regimens of aminoglycosides is described. Experiments were conducted to evaluate the impact of gentamicin and tobramycin concentration on the time required for the MICs for five Pseudomonas aeruginosa strains to revert to their original values (MIC reversion time [MRT]) following single and multiple 2-h aminoglycoside exposures to 8 and 24 mg/liter. Single 2-h aminoglycoside exposures to 8 mg/liter produced culture MRTs (gentamicin, 21.5 +/- 4.0 h; tobramycin, 22.3 +/- 2.8 h) that were significantly (P < 0.05) shorter than those measured following identical exposures to 24 mg/liter (gentamicin, 28.9 +/- 3.8 h; tobramycin, 26.8 +/- 3.1 h). However, three sequential 2-h exposures to 8 mg/liter, one exposure every 8 h, produced MRTs following the third exposure (gentamicin, 68.1 +/- 5.2 h; tobramycin, 77.8 +/- 7.8 h) that were significantly longer (P < 0.005) than those determined following three 2-h exposures to 24 mg/liter, one exposure every 24 h (gentamicin, 36.1 +/- 3.0 h; tobramycin, 34.5 +/- 3.0 h). In addition, the once-daily exposure regimen to 24 mg/liter consistently produced cultures with significantly (P < 0.005) higher aminoglycoside concentration/MIC ratios compared with those for cultures reexposed to 8 mg/liter once every 8 h. These data support the concept of once-daily aminoglycoside dosing.
本文描述了一种新的体外氨基糖苷类药物单次给药与每日分次给药方案的药效学比较。进行实验以评估庆大霉素和妥布霉素浓度对5株铜绿假单胞菌菌株的最低抑菌浓度（MIC）在单次和多次2小时氨基糖苷类药物暴露于8和24mg/L后恢复到原始值所需时间（MIC恢复时间[MRT]）的影响。单次2小时氨基糖苷类药物暴露于8mg/L产生的培养物MRT（庆大霉素，21.5±4.0小时；妥布霉素，22.3±2.8小时）显著（P<0.05）短于相同暴露于24mg/L后测得的MRT（庆大霉素，28.9±3.8小时；妥布霉素，26.8±3.1小时）。然而，连续三次2小时暴露于8mg/L，每8小时一次，在第三次暴露后产生的MRT（庆大霉素，68.1±5.2小时；妥布霉素，77.8±7.8小时）显著长于（P<0.005）三次2小时暴露于24mg/L，每24小时一次后测得的MRT（庆大霉素，36.1±3.0小时；妥布霉素，34.5±3.0小时）。此外，与每8小时重新暴露于8mg/L的培养物相比，每日一次暴露于24mg/L的方案始终产生氨基糖苷类药物浓度/MIC比值显著（P<0.005）更高的培养物。这些数据支持了氨基糖苷类药物每日一次给药的概念。
