Kemme D J, Daniel C I
Department of Medicine, Saint Joseph Hospital, Denver, Colo 80218.
South Med J. 1993 Jan;86(1):46-51. doi: 10.1097/00007611-199301000-00011.
Although clinical benefits for aminoglycoside dosing services have been suggested, this has not been clearly documented in a prospective fashion. Therefore, we randomly assigned patients to be dosed (1) by their physician (Physician dosing method), (2) by predicting an initial dosage (Predictive dosing method), or (3) by calculating an initial dosing regimen by measuring the pharmacokinetics for the individual patients after a loading dose (Individual dosing method). The patients' clinical response and nephrotoxicity were then evaluated. The individual dosing method resulted in erratic aminoglycoside levels, necessitating its elimination from the study. This group was not included in the final analysis. Of the 164 patients entering the study, 41 had a documented gram-negative infection, received aminoglycosides for more than 2 days, and had serum aminoglycoside levels measured. The predictive dosing method in these 41 patients produced statistically significant higher peak and lower trough levels, but there was no difference in the incidence of nephrotoxicity or clinical response. The 95% confidence intervals precluded any major clinical benefit in these patients with documented gram-negative infections. We question the previous findings of increased efficacy and decreased nephrotoxicity with the use of an aminoglycoside dosing service and suggest that larger studies be done.
尽管已有研究表明氨基糖苷类药物给药服务具有临床益处，但尚无前瞻性研究对此进行明确记录。因此，我们将患者随机分为三组给药：（1）由其医生给药（医生给药法）；（2）通过预测初始剂量给药（预测给药法）；（3）在给予负荷剂量后，通过测量个体患者的药代动力学来计算初始给药方案（个体给药法）。然后评估患者的临床反应和肾毒性。个体给药法导致氨基糖苷类药物水平不稳定，因此该组被排除在研究之外，未纳入最终分析。在164名参与研究的患者中，41名有革兰氏阴性菌感染记录，接受氨基糖苷类药物治疗超过2天，并测量了血清氨基糖苷类药物水平。这41名患者采用预测给药法产生的峰值水平在统计学上显著更高，谷值水平更低，但肾毒性发生率或临床反应并无差异。95%置信区间排除了这些有革兰氏阴性菌感染记录的患者有任何重大临床益处的可能性。我们对之前关于使用氨基糖苷类药物给药服务可提高疗效和降低肾毒性的研究结果表示质疑，并建议开展更大规模的研究。
