BACKGROUND Acute kidney injury is a major complication of vancomycin treatment, especially when it is co-administered with other nephrotoxins. OBJECTIVES This meta-analysis aims to comparatively assess the nephrotoxicity of antipseudomonal β-lactams when combined with vancomycin. DATA SOURCES Medline, Scopus, CENTRAL and Clinicaltrials.gov databases were systematically searched from inception through 20 August 2019. STUDY ELIGIBILITY CRITERIA Studies evaluating acute kidney injury risk following the concurrent use of antipseudomonal β-lactams and vancomycin were selected. PARTICIPANTS Adult and paediatric patients treated in hospital or intensive care unit. INTERVENTIONS Administration of vancomycin combined with any antipseudomonal β-lactam. METHODS Acute kidney injury incidence was defined as the primary outcome. Secondary outcomes included severity, onset, duration, need of renal replacement therapy, length of hospitalization and mortality. Quality of evidence was assessed using the ROBINS-I tool and the Confidence In Network Meta-Analysis approach. RESULTS Forty-seven cohort studies were included, with a total of 56 984 patients. In the adult population, the combination of piperacillin-tazobactam and vancomycin resulted in significantly higher nephrotoxicity rates than vancomycin monotherapy (odds ratio (OR) 2.05, 95% confidence intervals (CI) 1.17-3.46) and its concurrent use with meropenem (OR 1.84, 95% CI 1.02-3.10) or cefepime (OR 1.80, 95% CI 1.13-2.77). In paediatric patients, acute kidney injury was significantly higher with vancomycin plus piperacillin-tazobactam than vancomycin alone (OR 4.18, 95% CI 1.01-17.29) or vancomycin plus cefepime OR 3.71, 95% CI 1.08-11.24). No significant differences were estimated for the secondary outcomes. Credibility of outcomes was judged as moderate, mainly due to imprecision and inter-study heterogeneity. CONCLUSIONS The combination of vancomycin and piperacillin-tazobactam is associated with higher acute kidney injury rates than its parallel use with meropenem or cefepime. Current evidence is exclusively observational and is limited by inter-study heterogeneity. Randomized controlled trials are needed to verify these results and define preventive strategies to minimize nephrotoxicity risk.

中文翻译：

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同时使用抗假性β-内酰胺类和万古霉素引起的急性肾损伤：网络荟萃分析。

背景技术急性肾损伤是万古霉素治疗的主要并发症，特别是当其与其他肾毒素共同给药时。目的这项荟萃分析旨在比较评估与万古霉素合用时抗假性β-内酰胺类药物的肾毒性。数据来源从开始到2019年8月20日，系统地搜索了Medline，Scopus，CENTRAL和Clinicaltrials.gov数据库。研究合格标准选择了同时使用抗伪β-内酰胺和万古霉素后评估急性肾损伤风险的研究。参加者在医院或重症监护病房接受治疗的成年和儿科患者。干预措施万古霉素与任何抗假性β-内酰胺联用。方法急性肾损伤发生率定义为主要结局。次要结局包括严重程度，发作，持续时间，需要肾脏替代治疗，住院时间长短和死亡率。证据的质量使用ROBINS-I工具和网络中的置信度分析方法进行评估。结果纳入了47项队列研究，总共56 984例患者。在成年人群中，哌拉西林-他唑巴坦和万古霉素的组合产生的肾毒性比万古霉素单药治疗（比值比（OR）为2.05，95％置信区间（CI）为1.17-3.46）明显更高，并且与美罗培南同时使用（OR 1.84） ，95％CI 1.02-3.10）或头孢吡肟（OR 1.80，95％CI 1.13-2.77）。在儿科患者中，万古霉素加哌拉西林-他唑巴坦的急性肾损伤明显高于单独使用万古霉素（OR 4.18，95％CI 1.01-17）。29）或万古霉素加头孢吡肟或3.71，95％CI 1.08-11.24）。次要结局没有明显差异。结果的可信度被判断为中等，主要是由于不精确和研究间的异质性。结论万古霉素和哌拉西林-他唑巴坦的联合使用比美罗培南或头孢吡肟的并行使用具有更高的急性肾损伤率。当前的证据仅是观察性的，并且受到研究间异质性的限制。需要随机对照试验来验证这些结果并确定预防策略，以最大程度地降低肾毒性风险。结论万古霉素和哌拉西林-他唑巴坦的联合使用比美罗培南或头孢吡肟的并行使用具有更高的急性肾损伤率。当前的证据仅是观察性的，并且受到研究间异质性的限制。需要随机对照试验来验证这些结果并确定预防策略，以最大程度地降低肾毒性风险。结论万古霉素和哌拉西林-他唑巴坦的联合使用比美罗培南或头孢吡肟的并行使用具有更高的急性肾损伤率。当前的证据仅是观察性的，并且受到研究间异质性的限制。需要随机对照试验来验证这些结果并确定预防策略，以最大程度地降低肾毒性风险。