Abstract
Background
Empiric antimicrobial therapy for healthcare-acquired infections often includes vancomycin plus an antipseudomonal beta-lactam (AP-BL). These agents vary in risk for adverse events, including acute kidney injury (AKI) and Clostridium difficile infection (CDI). Studies have only examined these risks separately; thus, our objective was to simultaneously evaluate AKI and CDI risks with AP-BL in the same patient cohort.
Methods
This retrospective cohort study included 789,200 Veterans Health Administration medical admissions from July 1, 2010 through June 30, 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 (0.95-1.05), 0.92 (0.83-1.01), 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.
Influence of Beta-Lactam Infusion Strategy on Acute Kidney Injury
