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Critically ill patients are frequently treated with empirical antibiotic therapy, including vancomycin and β-lactams. Recent evidence suggests an increased risk of acute kidney injury (AKI) in patients who received a combination of vancomycin and piperacillin-tazobactam (VPT) compared with patients who received vancomycin alone or vancomycin in combination with cefepime (VC) or meropenem (VM), but most studies were conducted predominately in the non-critically ill population. A retrospective cohort study that included 2,492 patients was conducted in the intensive care units of a large university hospital with the primary outcome being the development of any AKI. The rates of any AKI, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, were 39.3% for VPT patients, 24.2% for VC patients, and 23.5% for VM patients ( P  &lt; 0.0001 for both comparisons). Similarly, the incidences of stage 2 and stage 3 AKI were also significantly higher for VPT patients than for the patients in the other groups. The rates of stage 2 and stage 3 AKI, respectively, were 15% and 6.6% for VPT patients, 5.8% and 1.8% for VC patients, and 6.6% and 1.3% for VM patients ( P  &lt; 0.0001 for both comparisons). In multivariate analysis, the use of vancomycin in combination with piperacillin-tazobactam was found to be an independent predictor of AKI (odds ratio [OR], 2.161; 95% confidence interval [CI], 1.620 to 2.883). In conclusion, critically ill patients receiving the combination of VPT had the highest incidence of AKI compared to critically ill patients receiving either VC or VM.

Incidence of Acute Kidney Injury in Critically Ill Patients Receiving Vancomycin with Concomitant Piperacillin-Tazobactam, Cefepime, or Meropenem