Nephrotoxicity with Vancomycin in the Pediatric Population: A Systematic Review and Meta-Analysis.

Background: Vancomycin is frequently used to treat methicillin-resistant Staphylococcus aureus infections in pediatric patients. Vancomycin exposure may lead to an increase in frequency of nephrotoxicity. Our aim was to conduct a systematic review to describe predictors of nephrotoxicity associated with vancomycin, including documented trough concentrations 15mg/L. We also aimed to use a meta-analysis to assess the impact of a vancomycin trough 15mg/L on nephrotoxicity. Methods: A literature search was performed using PubMed, Cochrane Library, Embase and Web of Sciences database. We included randomized clinical trials and observational studies evaluating the relationship between vancomycin troughs and nephrotoxicity in pediatric-age patients. Studies not measuring troughs or defining a different cut-off point than 15mg/L were excluded. Data on age, exclusion criteria, nephrotoxicity definition, risk factors for nephrotoxicity and vancomycin trough levels were extracted from selected papers. Results: Ten studies were identified for meta-analysis. All subjects had comparatively normal baseline serum creatinine values. Common risk factors identified included elevated (15mg/L) trough levels, renal impairment, hypovolemia and concurrent use of nephrotoxic medications. Troughs 15mg/L increased nephrotoxicity by 2.7-fold (odds ratio (OR), 2.71; 95% confidence interval: 1.82-4.05; I-2 = 40%; Q = 0.09). These odds were further increased among patients in the pediatric intensive care unit (OR, 3.61; 95% confidence interval: 1.21-10.74; I-2 = 45%; Q = 0.18). Conclusions: Though the rate of vancomycin-induced nephrotoxicity is increased in pediatric patients with higher vancomycin troughs, other factors such as intensive care unit admission, hypovolemia and concurrent nephrotoxic drug use appear to contribute to the development of nephrotoxicity.