Systematic Review and Meta-analysis of the Association of Acute Kidney Injury with the Concomitant Use of Vancomycin and Piperacillin-Tazobactam in Children

Concomitant use of vancomycin plus piperacillin-tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) in hospitalized adults. In this systematic review and meta-analysis, we searched PubMed and EMBASE for pediatric studies examining this hypothesis, with reference to vancomycin monotherapy or in combination with another beta-lactam antibiotic. Of 1,381 nonduplicate studies, 10 met our inclusion criteria. We performed a random-effects meta-analysis, based on crude odds ratios (ORs), and we accounted for both quality of included studies and publication bias. In primary analysis, concomitant vancomycin and TZP use yielded a statistically significant association with the development of AKI. More specifically, children with AKI had higher odds of having been exposed to vancomycin plus TZP than to vancomycin monotherapy (OR, 8.15; 95% confidence interval [CI], 3.49 to 18.99) or to vancomycin plus any other beta-lactam antibiotic (OR, 3.48; 95% CI, 2.71 to 4.46). On the basis of the results of the Newcastle-Ottawa scale quality assessment, a secondary analysis that included only higher-quality studies (6 of 10 studies) again yielded higher odds of exposure to vancomycin plus TZP than to vancomycin plus another beta-lactam antibiotic (OR, 3.76; 95% CI, 2.56 to 5.51). Notably, even after controlling for possible publication bias, our results remained statistically significant (OR, 3.09; 95% CI, 2.30 to 4.14). In conclusion, the concomitant use of vancomycin and TZP could be associated with AKI development and the clinical significance of this potential association needs to be studied further in the pediatric population.