SAN DIEGO, CA—The combination of vancomycin plus piperacillin/tazobactam resulted in a significantly higher incidence of acute kidney injury than when vancomycin was combined with cefepime, a study reported at IDWeek 2015.

Jessica Cox, PharmD, of the University of Kentucky HealthCare in Lexington, Kentucky, and colleagues explained that vancomycin is the mainstay of treatment for methicillin-resistant Staphylococcus infections at their institution, while beta-lactams are used to treat serious gram-negative infections. However, recent reports point to an increase in acute kidney injury when vancomycin is combined with beta-lactams.

To compare the incidence of acute kidney injury associated with vancomycin plus piperacillin/tazobactam or cefepime, Dr. Cox evaluated “all adult patients who received vancomycin in combination with either piperacillin/tazobactam or cefepime for at least 48 hours at our institution between September 2010 and September 2014.” Patients were excluded if they had severe chronic or structural kidney disease, required dialysis, were pregnant, had cystic fibrosis, had received intravenous (IV) contrast, or had been transferred from another hospital.

Using data from the University of Kentucky Enterprise Data Trust, acute kidney injury was evaluated in 2,375 patients using the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) criteria. Patients in the vancomycin plus piperacillin/tazobactam group (n=1,758) were matched 3:1 with those in the vancomycin plus cefepime group (n=617) based on age, sex, Charlson Comorbidity Index, baseline creatinine clearance, hypotension, number of nephrotoxicity risk factors, and median days of combination therapy.

The investigators found that incidence of any acute kidney injury was significantly higher in patients receiving vancomycin plus piperacillin/tazobactam compared to patients receiving vancomycin plus cefepime (30% vs. 18%, P<0.0001). This resulted in an average treatment effect of -10.9% (95% CI; -13.4 to -8.2%) after matching and counterfactual simulations. Dr. Cox added, “Vancomycin plus piperacillin/tazobactam treatment was associated with 1.9 times the odds of acute kidney injury” when controlling for other significant confounders after matching.

Specifically, vancomycin plus piperacillin/tazobactam was significantly higher than vancomycin plus cefepime for risk (P=0.004), injury (P=0.004), and failure (P=0.04). These difference were observed “despite higher vancomycin daily doses in the vancomycin plus cefepime group (2,034mg vs. 2,198mg, P<0.0001),” they reported.

No significant differences were observed in time to acute kidney injury, length of stay, or in-hospital mortality.