1 | Introduction
The glycopeptide, vancomycin is a narrow-band antibacterial agent with a triple bactericidal mechanism. It is widely used to treat severe infections caused by gram-positive bacteria such as the methicillin-resistant Staphylococcus aureus , Staphylococcus epidermidis , and Enterococcus .1–4 However, vancomycin has a narrow therapeutic window5 and is associated with serious adverse reactions. An increase of the drug-resistant strains as well as the phenomenon of ”MIC drift” lead to a rampant increase in the problems like poor efficacy, prolonged hospitalization, and high hospitalization costs. This has raised a concern about adjusting the dosage as well as monitoring the therapy of vancomycin worldwide. However, previous studies8–9showed that the proportion of conventional-dose administration reaching the recommended target concentration was relatively low. Increasing the dose of vancomycin can magnify the proportion of reaching trough concentration but it simultaneously increases the drug-induced nephrotoxicity. Therefore, to ensure adequate efficacy and safety, some studies were undertaken to increase the plasma concentration of vancomycin by prolonging the infusion time instead of increasing the drug dose.
To date, there are limited comparative studies on continuous and intermittent administration of vancomycin in children. Based on these studies, it is still unclear as to which method of vancomycin infusion and what concentration of vancomycin works better in the pediatric population with severe infection. Therefore, in-depth and comprehensive research is necessary to check whether the therapeutic effect can be improved by changing the IIV and prolonging the time of infusion. Also, studies should focus on identifying the mode of infusions of vancomycin which does not increase the risk of the drug side effect8–11. Here, we report a single-center randomized controlled trial (RCT) of CIV versus IIV in children in an intensive care unit (ICU). This study determined which of the two improves the target concentrations and AUC/MIC at the first steady-state level. Further, it also compared the clinical prognosis and the drug-related adverse effects between the CIV versus IIV, to explore the optimal regimen of vancomycin in children with a severe gram-positive bacterial infection.