Risk of Acute Kidney Injury and<i>Clostridioides difficile</i>Infection With Piperacillin/Tazobactam, Cefepime, and Meropenem With or Without Vancomycin

Abstract

BACKGROUND: Empiric antimicrobial therapy for healthcare-acquired infections often includes vancomycin plus an anti-pseudomonal beta-lactam (AP-BL). These agents vary in risk for adverse events, including acute kidney injury (AKI) and Clostrioides difficile infection (CDI). Studies have only examined these risks separately; thus, our objective was to evaluate AKI and CDI risks simultaneously with AP-BL in the same patient cohort. METHODS: This retrospective cohort study included 789 200 Veterans Health Administration medical admissions from 1 July 2010 through 30 June 2016. The antimicrobials examined were vancomycin, cefepime, piperacillin/tazobactam, and meropenem. Cox proportional hazards regression was used to contrast risks for AKI and CDI across individual target antimicrobials and vancomycin combination therapies, including adjustment for known confounders. RESULTS: With respect to the base rate of AKI among patients who did not receive a target antibiotic (4.6%), the adjusted hazards ratios for piperacillin/tazobactam, cefepime, and meropenem were 1.50 (95% CI: 1.43-1.54), 1.00 (.95-1.05), 0.92 (.83-1.01), respectively. Co-administration of vancomycin increased AKI rates (data not shown). Similarly, against the base rate of CDI (0.7%), these ratios were 1.21 (1.07-1.36), 1.89 (1.62-2.20), and 1.99 (1.55-2.56), respectively. Addition of vancomycin had minimal impact on CDI rates (data not shown). CONCLUSIONS: Piperacillin/tazobactam increased AKI risk, which was exacerbated by concurrent vancomycin. Cefepime and meropenem increased CDI risk relative to piperacillin/tazobactam. Clinicians should consider the risks and benefits of AP-BL when selecting empiric regimens. Further well-designed studies evaluating the global risks of AP-BL and patient specific characteristics that can guide empiric selection are needed.

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