Kidney Injury in Critically Ill Patients Treated with Vancomycin and Zosyn or an Alternative: A Systematic Review and Meta-Analysis

Background: Zosyn® (piperacillin-tazobactam; Pfizer Medical, New York, NY), a valuable antibiotic against gram-negative bacteria, combined with vancomycin (Z+V) is known for its high incidence of acute kidney injury (AKI), particularly in the intensive care unit (ICU), leading to the frequent use of alternatives for gram-negative coverage (Alt+V). Because there are limited data describing AKI on these alternative antibiotic agents, a systematic review and meta-analysis was conducted to determine if these regimens were indeed associated with decreased rates of AKI. Patients and Methods: A literature review was performed electronically from its inception to November 1, 2018, screening for relevant literature by title, abstract and full text according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines within the following databases: PubMed/Medline, CINAHL, Scopus, and Cochrane Central Register of Controlled Trials. Studies were included if they contained adults who had been admitted to the ICU for treatment and had received a combination of intravenous Z + V or Alt+V as well as had AKI measured during administration of these antibiotic agents. Studies were excluded if they represented pediatric populations, did not receive care in an ICU during their hospital admission, only received monotherapy for antibiotic treatment or received antibiotic treatment for less than 48 hours. Independent extraction was performed by two reviewers. Risk of bias was assessed using the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) methodology for retrospective studies. Random-effects models were used to calculate any differences between rates of AKI after Z + V or Alt + V. Results: Fourteen articles (totaling 30,399 patients) were included. All studies available were retrospective in design. Compared with Alt + V, Z + V was associated with a higher risk ratio of AKI (1.79; 95% confidence interval [CI], 1.46-2.19; p < 0.001). Cefepime (C + V) was the most common alternative to Zosyn, and Z + V was associated with higher rates of kidney injury compared with C + V (1.70; 95% CI, 1.36-2.12; p < 0.00001). However, there was substantial heterogeneity in the data collected as well as high risk of bias. Conclusions: Zosyn plus vancomycin is associated with more risk of AKI compared with Alt+V coverage in ICU adult populations. However, the conclusions were limited by the retrospective nature of the studies, high bias of included articles, and heterogeneity of the included studies.