Impact of Antimicrobial Drug-Drug Interactions on Acute Kidney Injury after Allogeneic Hematopoietic Cell Transplantation

•Various antimicrobials were identified as high risk factors for acute kidney injury (AKI), which is related to significantly poorer overall survival.•Drug-drug interactions, including that between vancomycin and tazobactam/piperacillin, have been shown to synergistically increase the risk of AKI. Acute kidney injury (AKI) is one of the major complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The use of multiple antimicrobials is one of the major causes of post-transplantation AKI, owing to the potential nephrotoxicity of each agent and of drug-drug interactions (DDIs). No satisfactory reports on DDIs the field of allo-HSCT have been published. We performed a retrospective analysis to compare the incidence of AKI within 100 days post-transplantation. A total of 465 allo-HSCTs in 416 patients were analyzed, and the cumulative incidence of AKI was 40.0%. AKI was associated with significantly reduced overall survival (hazard ratio [HR], 2.66; 95% confidence interval [CI] 1.95 to 3.55; P < .01) and increased transplantation-related mortality (HR, 4.77, 95% CI, 2.90 to 7.88; P < .01). A higher incidence of AKI was significantly associated with the use of ciprofloxacin, cefepime, tazobactam/piperacillin, meropenem, vancomycin, liposomal amphotericin B, ganciclovir, and foscarnet. Among these drugs, combinations of vancomycin plus tazobactam/piperacillin (HR, 2.23; P = .09 for interaction), ganciclovir plus cefepime (HR, 5.93; P = .04), and ganciclovir plus meropenem (HR, 2.63; P = .12) synergistically increased the risk of AKI, whereas combinations involving teicoplanin did not. This is the first report dealing with DDIs after allo-HSCT, indicating that such combinations should be avoided to preserve renal function and reduce AKI-related morbidity and mortality.