关于接受多黏菌素治疗患者肾毒性和神经毒性估计发生率的系统评价。
Systematic review on estimated rates of nephrotoxicity and neurotoxicity in patients treated with polymyxins.
作者信息
Wagenlehner Florian, Lucenteforte Ersilia, Pea Federico, Soriano Alex, Tavoschi Lara, Steele Victoria R, Henriksen Anne Santerre, Longshaw Christopher, Manissero Davide, Pecini Raymond, Pogue Jason M
机构信息
Clinic for Urology, Pediatric Urology and Andrology, Justus-Liebig-University, Giessen, Germany.
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
出版信息
Clin Microbiol Infect. 2021 Jan 6. doi: 10.1016/j.cmi.2020.12.009.
BACKGROUND
Nephrotoxicity and neurotoxicity are commonly associated with polymyxin treatment; however, the emergence of multidrug-resistant Gram-negative bacteria with limited therapeutic options has resulted in increased use of polymyxins.
OBJECTIVES
To determine the rates of nephrotoxicity and neurotoxicity during polymyxin treatment and whether any factors influence these.
DATA SOURCES
Medline, Embase and Cochrane Library databases were searched on 2 January 2020.
STUDY ELIGIBILITY CRITERIA
Studies reporting nephrotoxicity and/or neurotoxicity rates in patients with infections treated with polymyxins were included. Reviews, meta-analyses and reports not in English were excluded.
PARTICIPANTS
Patients hospitalized with infections treated with systemic or inhaled polymyxins were included. For comparative analyses, patients treated with non-polymyxin-based regimens were also included.
METHODS
Meta-analyses were performed using a random-effects model; subgroup meta-analyses were conducted where data permitted using a mixed-effects model.
RESULTS
In total, 237 reports of randomized controlled trials, cohort and case-control studies were eligible for inclusion; most were single-arm observational studies. Nephrotoxic events in 35,569 patients receiving polymyxins were analysed. Overall nephrotoxicity rate was 0.282 (95% confidence interval (CI) 0.259-0.307). When excluding studies where >50% of patients received inhaled-only polymyxin treatment or nephrotoxicity assessment was by methods other than internationally recognized criteria (RIFLE, KDIGO or AKIN), the nephrotoxicity rate was 0.391 (95% CI 0.364-0.419). The odds of nephrotoxicity were greater with polymyxin therapies compared to non-polymyxin-based regimens (odds ratio 2.23 (95% CI 1.58-3.15); p < 0.001). Meta-analyses showed a significant effect of polymyxin type, dose, patient age, number of concomitant nephrotoxins and use of diuretics, glycopeptides or vasopressors on the rate of nephrotoxicity. Polymyxin therapies were not associated with a significantly different rate of neurotoxicity than non-polymyxin-based regimens (p 0.051). The overall rate of neurotoxicity during polymyxin therapy was 0.030 (95% CI 0.020-0.043).
CONCLUSIONS
Polymyxins are associated with a higher risk of nephrotoxicity than non-polymyxin-based regimens.
背景
肾毒性和神经毒性通常与多粘菌素治疗相关；然而，由于治疗选择有限的多重耐药革兰氏阴性菌的出现，多粘菌素的使用有所增加。
目的
确定多粘菌素治疗期间肾毒性和神经毒性的发生率，以及是否有任何因素影响这些发生率。
数据来源
2020年1月2日检索了Medline、Embase和Cochrane图书馆数据库。
研究入选标准
纳入报告多粘菌素治疗感染患者肾毒性和/或神经毒性发生率的研究。排除综述、荟萃分析和非英文报告。
参与者
纳入接受全身或吸入多粘菌素治疗感染的住院患者。为进行比较分析，还纳入接受非多粘菌素方案治疗的患者。
方法
采用随机效应模型进行荟萃分析；在数据允许的情况下，使用混合效应模型进行亚组荟萃分析。
结果
总共237篇随机对照试验、队列研究和病例对照研究报告符合纳入标准；大多数是单臂观察性研究。分析了35569例接受多粘菌素治疗患者的肾毒性事件。总体肾毒性发生率为0.282（95%置信区间（CI）0.259 - 0.307）。当排除超过50%的患者仅接受吸入多粘菌素治疗或肾毒性评估采用国际认可标准（RIFLE、KDIGO或AKIN）以外方法的研究时，肾毒性发生率为0.391（95% CI 0.364 - 0.419）。与非多粘菌素方案相比，多粘菌素治疗导致肾毒性的几率更高（优势比2.23（95% CI 1.58 - 3.15）；p < 0.001）。荟萃分析表明多粘菌素类型、剂量、患者年龄、同时使用的肾毒性药物数量以及利尿剂、糖肽类或血管加压药的使用对肾毒性发生率有显著影响。多粘菌素治疗与非多粘菌素方案相比，神经毒性发生率无显著差异（p = 0.051）。多粘菌素治疗期间的总体神经毒性发生率为0.030（95% CI 0.020 - 0.043）。
结论
与非多粘菌素方案相比，多粘菌素导致肾毒性的风险更高。
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