Zelenitsky S A, Karlowsky J A, Hoban D J, Kabani A, Zhanel G G
Faculty of Pharmacy, University of Manitoba, Winnipeg, Canada.
Chemotherapy. 1998 Jan-Feb;44(1):1-6. doi: 10.1159/000007083.
The purpose of this study was to compare once daily (To24) and thrice daily (To8) tobramycin dosing regimens alone and in combination with ceftazidime, ciprofloxacin and imipenem against a clinical and ATCC strain of Pseudomonas aeruginosa. A one-compartment in vitro pharmacodynamic model was used to simulate bacteremic infection. Pharmacodynamic parameters, including rate of bacterial kill following the first dose or time to achieve a 99.9% reduction in bacterial counts (T99.9%), extent of bacterial kill with subsequent doses and bacterial count at 24 h were characterized for each regimen. Compared to To8 alone, the combination regimens had a shorter T99.9% (p = 0.045) and greater extent of bacterial kill following the first dose (p = 0.045). Compared to To24 alone, the combination regimens demonstrated similar rates (p = 0.067) and extents of bacterial kill following the first dose (p = 0.32), however, produced lower bacterial counts at 24 h (p = 0.045). The various combination regimens appeared equally effective considering rate and extent of bacterial kill following the first dose and residual inocula at 24 h. Ciprofloxacin-containing regimens demonstrated the most bacterial kill with subsequent doses, however, bacterial counts at 24 h were similar to those of other combination regimens.
本研究的目的是比较每日一次（To24）和每日三次（To8）的妥布霉素给药方案单独使用以及与头孢他啶、环丙沙星和亚胺培南联合使用时，对临床分离株和美国典型培养物保藏中心（ATCC）的铜绿假单胞菌菌株的抗菌效果。采用单室体外药效学模型模拟菌血症感染。对每种给药方案的药效学参数进行了表征，包括首剂后的细菌杀灭率或达到细菌计数降低99.9%的时间（T99.9%）、后续剂量的细菌杀灭程度以及24小时时的细菌计数。与单独使用To8相比，联合给药方案的T99.9%更短（p = 0.045），首剂后的细菌杀灭程度更大（p = 0.045）。与单独使用To24相比，联合给药方案首剂后的细菌杀灭率（p = 0.067）和程度（p = 0.32）相似，但24小时时的细菌计数更低（p = 0.045）。考虑到首剂后的细菌杀灭率和程度以及24小时时的残留接种量，各种联合给药方案似乎同样有效。含环丙沙星的给药方案后续剂量的细菌杀灭效果最佳，然而，24小时时的细菌计数与其他联合给药方案相似。
