Abstract
OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) infections among children are escalating annually. Vancomycin serves as the frontline therapeutic agent against MRSA infections. However, determining the therapeutic window that maximizes efficacy while minimizing the risk of toxicity for vancomycin in pediatric patients remains a challenge. This study aimed to explore a therapeutic window for vancomycin in pediatric patients. METHODS: This retrospective study collected data from hospitalized children aged 1 month to 18 years, who underwent routine therapeutic drug monitoring for vancomycin. We analyzed the distribution patterns of vancomycin concentrations in these patients. Factors influencing clinical outcomes and adverse reaction (nephrotoxicity) were investigated. ROC analysis was used to establish the therapeutic window for vancomycin in pediatric patients. RESULTS: A comprehensive dataset encompassing 183 pediatric patients with 330 samples was analyzed. The mean trough concentration (C(min)) of vancomycin was 7.6 ± 5.5 mg/L. 74.3% of patients exhibited concentrations below the conventionally recommended therapeutic window of 10-20 mg/L. Patients responding positively to treatment exhibited significantly higher C(min) values (8.4 ± 5.7 mg/L) compared to those with treatment failure (5.9 ± 4.4 mg/L, P = 0.006). Similarly, patients who developed nephrotoxicity had significantly elevated C(min) levels (17.8 ± 5.3 mg/L) compared to those without nephrotoxicity (6.4 ± 3.9 mg/L, P < 0.001). Both univariate and multivariate logistic regressions revealed that the C(min) of vancomycin was the predictor of both clinical outcomes and nephrotoxicity. Furthermore, receiver operating characteristic curve analysis pinpointed that C(min) of vancomycin with 5.9 mg/L (AUC = 0.643) and 14.8 mg/L (AUC = 0.960) associated with clinical effectiveness and safety, respectively. When the therapeutic exposure targets established for adults are used as a reference, a substantial proportion of pediatric patients are found to have subtherapeutic vancomycin levels. CONCLUSION: Based on our findings, we suggest a potential therapeutic window of 5.9-14.8 mg/L for vancomycin in pediatric patients, which may help optimize treatment efficacy and reduce toxicity. Further prospective studies are warranted to validate this range.