Nephrotoxic Risk Associated With Combination Therapy of Vancomycin and Piperacillin-Tazobactam in Critically Ill Patients With Chronic Kidney Disease

Background: The combination of vancomycin and piperacillin-tazobactam (VPT) has been associated with acute kidney injury (AKI) in hospitalized patients when compared to similar combinations. Additional studies examining this nephrotoxic risk in critically ill patients have not consistently demonstrated the aforementioned association. Furthermore, patients with baseline renal dysfunction have been excluded from almost all of these studies, creating a need to examine the risk in this patient population. Methods: This was a retrospective cohort analysis of critically ill adults with baseline chronic kidney disease (CKD) who received vancomycin plus an anti-pseudomonal beta-lactam at Emory University Hospital. The primary outcome was incidence of AKI. Secondary outcomes included stage of AKI, time to development of AKI, time to return to baseline renal function, new requirement for renal replacement therapy, intensive care unit and hospital length of stay, and in-hospital mortality. Results: A total of 109 patients were included. There was no difference observed in the primary outcome between the VPT (50%) and comparator (58%) group (P = .4), stage 2 or 3 AKI (15.9% vs 6%; P = .98), time to AKI development (1.7 vs 2 days; P = .5), time to return to baseline renal function (4 vs 3 days; P = .2), new requirement for RRT (4.5% vs 1.5%; P = .3), ICU length of stay (7.3 vs 7.4 days; P = .9), hospital length of stay (19.3 vs 20.1 days; P = .87), or in-hospital mortality (15.9% vs 10.8%; P = .4). A significant difference was observed in the duration of antibiotic exposure (3.32 vs 2.62 days; P = .045 days). Conclusion: VPT was not associated with an increased risk of AKI or adverse renal outcomes. Our findings suggest that the use of this antibiotic combination should not be avoided in this patient population. More robust prospective studies are warranted to confirm these findings.