Nicolau D P, Freeman C D, Belliveau P P, Nightingale C H, Ross J W, Quintiliani R
Department of Pharmacy, Hartford Hospital, Connecticut 06102, USA.
Antimicrob Agents Chemother. 1995 Mar;39(3):650-5. doi: 10.1128/AAC.39.3.650.
Once-daily aminoglycoside (ODA) regimens have been instituted to maximize bacterial killing by optimizing the peak concentration/MIC ratio and to reduce the potential for toxicity. We initiated an ODA program at our institution that utilizes a fixed 7-mg/kg intravenous dose with a drug administration interval based on estimated creatinine clearance: > or = 60 ml/min every 24 h (q24h), 59 to 40 ml/min q36h, and 39 to 20 ml/min q48h. Subsequent interval adjustments are made by using a single concentration in serum and a nomogram designed for monitoring of ODA therapy. Since initiation of the program, 2,184 patients have received this ODA regimen. The median dose was 450 (range, 200 to 925) mg, while the median length of therapy was 3 (range, 1 to 26) days. The median age of the population was 46 (range, 13 to 97) years. Gentamicin accounted for 94% of the aminoglycoside use, and the majority (77%) of patients received the drug q24h. The 36-, 48-, and > 48-h intervals were used for 15, 6, and 2% of this population, respectively. Three patients exhibited clinically apparent ototoxicity. Twenty-seven patients (1.2%) developed nephrotoxicity (the Hartford Hospital historical rate is approximately 3 to 5%) after a median of 7 (range, 3 to 19) days of therapy. On the basis of a prospective evaluation of 58 patients and follow-up of additional patients via clinician reports, we have noted no apparent alterations in clinical response with our ODA program. This ODA program appears to be clinically effective, reduces the incidence of nephrotoxicity, and provides a cost-effective method for administration of aminoglycosides by reducing ancillary service time and serum aminoglycoside determinations.
每日一次氨基糖苷类(ODA)给药方案已被采用,通过优化峰浓度/最低抑菌浓度(MIC)比值来最大化细菌杀伤效果,并降低毒性风险。我们在本机构启动了一项ODA计划,该计划采用固定的7mg/kg静脉给药剂量,给药间隔根据估计的肌酐清除率确定:肌酐清除率≥60ml/min时每24小时(q24h)给药一次,59至40ml/min时每36小时给药一次,39至20ml/min时每48小时给药一次。随后通过测定血清中的单一浓度并使用专为监测ODA治疗设计的列线图来调整给药间隔。自该计划启动以来,已有2184例患者接受了这种ODA给药方案。中位剂量为450(范围200至925)mg,而中位治疗时长为3(范围1至26)天。患者的中位年龄为46(范围13至97)岁。庆大霉素占氨基糖苷类药物使用量的94%,大多数(77%)患者每24小时接受一次该药治疗。该人群中分别有15%、6%和2%的患者采用了每36小时、每48小时和超过48小时的给药间隔。3例患者出现了临床明显的耳毒性。27例患者(1.2%)在中位治疗7(范围3至19)天后出现了肾毒性(哈特福德医院的历史发生率约为3%至5%)。基于对58例患者的前瞻性评估以及通过临床医生报告对其他患者的随访,我们发现我们的ODA计划在临床反应方面没有明显变化。这种ODA计划似乎在临床上是有效的,降低了肾毒性的发生率,并且通过减少辅助服务时间和血清氨基糖苷类药物测定,提供了一种具有成本效益的氨基糖苷类药物给药方法。