Department of Pharmacy Services, Sinai-Grace Hospital, Detroit Medical Center, Michigan, USA.
Clin Infect Dis. 2011 Nov;53(9):879-84. doi: 10.1093/cid/cir611. Epub 2011 Sep 7.
Colistin, originally abandoned due to high rates of nephrotoxicity, has been recently reintroduced due to activity against carbapenem-resistant Gram-negative organisms. Recent literature, largely obtained from outside the United States, suggests a lower rate of nephrotoxicity than historically reported.
A retrospective cohort of all patients who received colistin for ≥ 48 hours at the Detroit Medical Center over a 5-year period was performed to determine the rate of colistin-associated nephrotoxicity as defined by the RIFLE criteria.
Fifty-four (43%) patients in the cohort developed nephrotoxicity. Patients who experienced nephrotoxicity after colistin administration were in the Risk (13%), Injury (17%), or Failure (13%) categories per RIFLE criteria. Patients who developed nephrotoxicity received significantly higher mean doses than those who did not (5.48 mg/kg per day vs 3.95 mg/kg per day; P < .001), and the toxicity occurred in a dose-dependent fashion. Independent predictors for nephrotoxicity were a colistin dose of ≥ 5.0 mg/kg per day of ideal body weight (odds ratio [OR], 23.41; 95% confidence interval [CI], 5.3-103.55), receipt of concomitant rifampin (OR, 3.81; 95% CI, 1.42-10.2), and coadministration of ≥ 3 concomitant nephrotoxins (OR, 6.80; 95% CI, 1.42-32.49).
In this retrospective cohort, nephrotoxicity (as defined by RIFLE criteria) occurred among 43% of treated patients in a dose-dependent manner. Higher colistin doses, similar to those commonly used in the United States, led to a relatively high rate of nephrotoxicity. These data raise important questions regarding the safe use of colistin in the treatment of multidrug-resistant pathogens.
多黏菌素最初因肾毒性高而被弃用,但由于其对碳青霉烯类耐药的革兰氏阴性菌具有活性,最近又重新被使用。近期的文献主要来自美国以外的地区,表明其肾毒性低于历史报道。
对底特律医疗中心在 5 年内接受多黏菌素治疗超过 48 小时的所有患者进行回顾性队列研究,以确定符合 RIFLE 标准的多黏菌素相关性肾毒性的发生率。
队列中有 54 例(43%)患者发生肾毒性。根据 RIFLE 标准,接受多黏菌素治疗后发生肾毒性的患者处于风险(13%)、损伤(17%)或衰竭(13%)状态。发生肾毒性的患者接受的平均剂量明显高于未发生肾毒性的患者(5.48 毫克/千克/天比 3.95 毫克/千克/天;P<.001),且毒性呈剂量依赖性。肾毒性的独立预测因素为多黏菌素剂量≥5.0 毫克/千克/理想体重/天(比值比[OR],23.41;95%置信区间[CI],5.3-103.55)、同时使用利福平(OR,3.81;95% CI,1.42-10.2)和同时使用≥3 种肾毒性药物(OR,6.80;95% CI,1.42-32.49)。
在这项回顾性队列研究中,接受治疗的患者中有 43%(按 RIFLE 标准定义)发生了剂量依赖性肾毒性。较高的多黏菌素剂量与美国常用剂量相似,导致肾毒性发生率相对较高。这些数据对多黏菌素治疗多重耐药病原体的安全使用提出了重要问题。