Clinicalapplication Value Of Vancomycin Pharmacokinetic/Pharmacodynamic Parameters In Children With Severe Infection

Objective:To explore the correlation between vancomycin pharmacokinetic/pharmacodynamic parameters and therapeutic efficacy,vancomycin-related nephrotoxicity in children with severe infection and determine the appropriate threshold.Methods:The information of hospitalized children with severe infection treated with vancomycin in the Department of Intensive Care,Children’s Hospital Affiliated to Chongqing Medical University from September 2018 to January 2021 was collected retrospectively.Univariate analysis was used to analyze the correlation between vancomycin pharmacokinetic/pharmacodynamic parameters and therapeutic efficacy or vancomycin-related nephrotoxicity.Binary logistic regression was used to analyze the risk factors of vancomycin-related nephrotoxicity.Area under the curve over 24 hours(AUC_0-24)threshold was determined by receiver operating characteristic curve.Results:Among the 110 cases included,76 cases（69.1%）were clinically effective.There were 66 cases with definite pathogen detection,49 cases（74.2%）had pathogen clearance.Vancomycin-related nephrotoxicity occurred in 15 cases of 110 cases（13.6%）.Univariate analysis showed that there were no significant differences in the severity of the disease,drug utilization,and therapeutic drug monitoring between the effective group and the ineffective group（P>0.05）.Univariate analysis showed that there were no significant differences in the severity of the disease,drug utilization,and therapeutic drug monitoring between the pathogen-cleared group and pathogen-uncleaned group（P>0.05）.Multivariate analysis showed that vancomycin treatment duration,trough concentration and AUC_0-24were the risk factors for vancomycin-related nephrotoxicity（P<0.05）.AUC_0-24and nephrotoxicity receiver operating characteristic curve indicate that AUC_0-24<537.18 mg·h/L may be a suitable threshold for predicting vancomycin-related nephrotoxicity.Conclusion:In our study,it was not found that the trough concentration,peak concentration and AUC_0-24of vancomycin were significantly related to the therapeutic efficacy and bacterial clearance in children with severe infection,but the trough concentration and AUC_0-24are closely related to vancomycin-related nephrotoxicity.AUC_0-24can be used for therapeutic drug monitoring to reduce the risk of nephrotoxicity.More multicenter and large sample prospective studies are needed to further explore the appropriate threshold of AUC_0-24.