Piperacillin-Tazobactam Plus Vancomycin Equals Acute Kidney Injury: Does It Add Up?*
In this issue of Pediatric Critical Care Medicine, Holsen et al (4) retrospectively compared the rate of AKI in critically ill children receiving vancomycin plus either piperacillin-tazobactam (PTZ) or ceftriaxone. Over a 2-year period in the PICU at the Women and Children’s Hospital of Buffalo, 93 children were identified to meet the inclusion of over 2 months of age, received either of the studied antibiotic combination for at least 48 hours, and had a documented serum creatinine (SCr) within 24 hours of antibiotic initiation and throughout the duration of therapy. Patients with AKI within 24 hours of admission or who received renal replacement therapy were excluded. AKI was defined by pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease criteria (5) and 50% increase in SCr from baseline which was adjusted based on fluid balance. The primary objective was the rate of AKI with PTZ + vancomycin and ceftriaxone + vancomycin; secondary objectives included evaluation of AKI risk factors, description of vancomycin use, and differences in mortality and length of stay in the AKI and non-AKI groups.
In this investigation, 18 children developed AKI based on adjusted SCr definition, with a frequency of AKI of 25.9% in the PTZ + vancomycin group and 8.6% in the ceftriaxone + vancomycin group (p = 0.041). The PTZ + vancomycin and ceftriaxone + vancomycin treatment groups were similar in baseline characteristics with the exception of the antibiotic indication and the initial 24-hour vancomycin area under the curve. Patients receiving PTZ + vancomycin were more likely to be immunocompromised (10% vs 0%) and treated for empiric fever or pneumonia. The multivariate logistic regression revealed that the PTZ + vancomycin combination increased the risk of AKI when compared with ceftriaxone + vancomycin (adjusted OR, 4.55; 95% CI, 1.11–18.7; p = 0.035). Similarly, vancomycin trough serum concentrations at or above 15 µg/mL increased the risk of AKI (adjusted OR, 4.12; 95% CI, 1.12–15.2; p = 0.033). Vasopressor use was also found to increase risk of AKI (adjusted OR, 3.73; 95% CI, 1.14–12.3; p = 0.03). Length of stay was prolonged in the AKI group (median 18 vs 6.21 d; p = 0.017), but no mortality difference was observed (AKI 5.56% vs non-AKI 6.67%; p = 1.00).
Beta-lactam antibiotics are not typically identified as nephrotoxic and usually viewed as having a mild adverse effect profile when compared with vancomycin. However, there is growing literature to suggest otherwise. A comparative study of vancomycin monotherapy versus PTZ + vancomycin combination in adults described a rate of AKI of 8% in the monotherapy group and 16.3% in the combination group (p = 0.