Internal Medicine, Department of Cardiothoracic Sciences, University of Naples S.U.N. and AORN Ospedali dei Colli, Monaldi Hospital, Naples, Italy.
Medical Statistics, Department of Medicine and Public Health, University of Naples S.U.N., Naples, Italy.
Clin Microbiol Infect. 2016 Dec;22(12):984-989. doi: 10.1016/j.cmi.2016.08.004. Epub 2016 Aug 18.
The study aimed to prospectively assess incidence and risk factors for colistin-associated nephrotoxicity. This is a secondary analysis of a multicentre, randomized clinical trial, comparing efficacy and safety of colistin versus the combination of colistin plus rifampicin in severe infections due to extensively drug-resistant (XDR) Acinetobacter baumannii. The primary end point was acute kidney injury (AKI) during colistin treatment, assessed using the AKI Network Criteria, and considering death as a competing risk. A total of 166 adult patients without baseline kidney disease on renal replacement therapy were studied. All had life-threatening infections due to colistin-susceptible XDR A. baumannii. Patients received colistin intravenously at the same initial dose (2 million international units (MIU) every 8 h) with predefined dose adjustments according to the actual renal function. Serum creatinine was measured at baseline and at days 4, 7, 11, 14 and 21 (or last day of therapy when discontinued earlier). Outcomes assessed were 'time to any kidney injury' (AKI stages 1-3) and 'time to severe kidney injury' (considering only AKI stages 2-3 as events). When evaluating overall mortality, AKI occurrence was modelled as a time-dependent variable. AKI was observed in 84 patients (50.6%, stage 1 in 40.4%), with an incidence rate of 5/100 person-days (95% CI 4-6.2). Risk estimates of AKI at 7 and 14 days were 30.6% and 58.8%. Age and previous chronic kidney disease were significantly associated with any AKI in multivariable analysis. Neither 'any' nor 'severe AKI' were associated with on-treatment mortality (p 0.32 and p 0.54, respectively). AKI occurs in one-third to one-half of colistin-treated patients and is more likely in elderly patients and in patients with kidney disease. As no impact of colistin-associated AKI on mortality was found, this adverse event should not represent a reason for withholding colistin therapy, whenever indicated.
本研究旨在前瞻性评估黏菌素相关性肾毒性的发生率和危险因素。这是一项多中心、随机临床试验的二次分析，比较了黏菌素与黏菌素联合利福平治疗广泛耐药（XDR）鲍曼不动杆菌引起的严重感染的疗效和安全性。主要终点是黏菌素治疗期间急性肾损伤（AKI），使用 AKI 网络标准评估，并考虑死亡为竞争风险。共纳入 166 名无基线肾脏疾病且未接受肾脏替代治疗的成年患者。所有患者均患有因黏菌素敏感的 XDR 鲍曼不动杆菌引起的危及生命的感染。所有患者均接受静脉注射黏菌素，初始剂量相同（每 8 小时 200 万国际单位（MIU）），并根据实际肾功能进行预设剂量调整。在基线时和第 4、7、11、14 和 21 天（或提前停止治疗时的最后一天）测量血清肌酐。评估的结局是“任何肾脏损伤时间”（AKI 1-3 期）和“严重肾脏损伤时间”（仅将 AKI 2-3 期视为事件）。在评估总死亡率时，将 AKI 发生作为时间依赖性变量进行建模。84 名患者（50.6%，其中 40.4%为 AKI 1 期）出现 AKI，发生率为 5/100 人-日（95%CI 4-6.2）。7 天和 14 天时 AKI 的风险估计分别为 30.6%和 58.8%。多变量分析显示，年龄和既往慢性肾脏病与任何 AKI 显著相关。无论“任何”还是“严重 AKI”均与治疗期间死亡率无关（p 值分别为 0.32 和 0.54）。黏菌素治疗患者中有三分之一到一半会发生 AKI，老年患者和有肾脏疾病的患者更有可能发生 AKI。由于未发现黏菌素相关性 AKI 对死亡率有影响，因此只要有指征，这种不良事件不应成为拒绝黏菌素治疗的理由。
