Acute Kidney Injury Associated with Combination Antimicrobial Therapy in the Medical Information Mart for Intensive Care (MIMIC) III Database

BACKGROUND: Increased acute kidney injury (AKI) incidence is linked with coadministration of vancomycin (VAN) and piperacillin-tazobactam (TZP) in the general hospital population when compared with VAN and cefepime (FEP); however, this phenomenon was not found in critically ill patients. METHODS: Patients receiving VAN in combination with FEP or TZP for at least 48 hours during an intensive care unit stay were included in this retrospective review. AKI was defined with the Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria. Exposure to common nephrotoxins was captured within 24 hours of combination therapy initiation through the entire treatment window. Basic descriptive statistics were performed, along with bivariable and multivariable logistic regression models of AKI odds. RESULTS: In total, 2230 patients were included, with 773 receiving FEP+VAN and 1457 receiving TZP+VAN. The groups were well balanced at baseline in most covariates, with the exception of hepatorenal syndrome diagnosis (TZP+VAN 1.4% vs. FEP+VAN 0.3%, P = 0.02) and vasopressor exposure (TZP+VAN 26.2% vs 21.5%, P = 0.01) being more common in the TZP+VAN group. Patients in the FEP+VAN group had a higher underlying severity of disease (Charlson comorbidity index [CCI] 2.7 vs. 2.3, P =0.0002). AKI incidence was higher in the TZP+VAN cohort (35.1% vs. 26.5%, P = 0.00004), with each stratification of the RIFLE criteria being higher. The time until onset of AKI was similar between groups (TZP+VAN median 1 [0–3] days vs. FEP+VAN 1 [0–4] days, P =0.2). After multivariable logistic regression, TZP+VAN therapy was associated with an adjust odds ratio (aOR) of AKI of 1.54 (95% confidence interval [CI] 1.25–1.89) compared with FEP+VAN. Other variables associated with increased odds of AKI included: age >= 65, duration of antibiotic therapy, higher baseline renal function, sepsis, endocarditis, hepatorenal syndrome, thiazide diuretic exposure, and increased CCI. CONCLUSION: Treatment with TZP+VAN is associated with significant increases in AKI incidence among critically ill patients, independent of other risks for AKI. DISCLOSURES: All authors: No reported disclosures.