Systematic review and meta-analysis to explore optimal therapeutic range of vancomycin trough level for infected paediatric patients with Gram-positive pathogens to reduce mortality and nephrotoxicity risk.

The aim of this study was to investigate the association between vancomycin trough level and clinical outcomes (mortality and nephrotoxicity) among infected paediatric patients with Gram-positive pathogens. We systematically searched the Scopus, EMBASE, Cochrane Central Register of Controlled Trials, PubMed and CINAHL databases up to March 2020. A total of seven retrospective cohort or case-control studies were included to compare clinical effects and safety: three studies set the threshold of vancomycin trough level at 10 mg/L and the others set it at 15 mg/L. Our analysis showed that vancomycin trough level of 10-15 mg/L was associated with significantly lower mortality [<10 mg/L vs. ≥10 mg/L, odds ratio (OR) = 3.21, 95% confidence interval (CI) 1.74-5.91; and <15 mg/L vs. ≥15 mg/L, OR = 0.31, 95% CI 0.10-0.95). The high vancomycin trough group (≥10 mg/L or ≥15 mg/L) showed a higher incidence of nephrotoxicity (<10 mg/L vs. ≥10 mg/L, OR = 0.06, 95% CI 0.03-0.12; and <15 mg/L vs. ≥15 mg/L, OR = 0.28, 95% CI 0.12-0.65). This is the first meta-analysis to reveal the optimal therapeutic range of vancomycin trough level in children. Our findings strongly suggest a superior benefit of vancomycin trough of 10-15 mg/L for paediatric patients.