Switching From Intermittent to Continuous Infusion of Vancomycin in Critically Ill Patients : Toward a More Robust Exposure

BACKGROUND: To increase target attainment rates, switching the mode of administration from intermittent (InI) to continuous infusion (CoI) has been proposed. In this study, target attainment rates and interpatient variation in exposure were compared between vancomycin InI- and CoI-treated critically ill patients. METHODS: An observational cohort study was conducted among critically ill patients admitted to a level-2 intensive care unit. Adult patients (18 years or older) treated with intravenous vancomycin for various indications, including sepsis, pneumonia, and endocarditis between 2007 and 2013 were eligible for inclusion. In 2010, vancomycin mode of administration switched from intermittent to continuous. Vancomycin was administered through intravenous infusion, and dosing was guided by therapeutic drug monitoring. Target attainment rates and variations in serum concentration and estimated area under the curve (AUC) were compared between groups. RESULTS: The target attainment rate for therapeutic vancomycin exposure was higher in the group treated with CoI than in patients treated with InI (48% versus 19%, P < 0.001). Furthermore, between-patient variation in vancomycin serum concentration was nearly twice as high in intermittently infused patients compared with continuously infused patients. Finally, the correlation between serum concentration and AUC was stronger among patients on vancomycin continuous infusion than that of the intermittently dosed group (r 0.93 versus 0.72). CONCLUSIONS: Switching from intermittent to continuous infusion of vancomycin in a critically ill population provided higher target attainment rates and a more robust drug exposure. Furthermore, continuous infusion yielded stronger concentration-AUC correlations facilitating a single sample therapeutic drug monitoring strategy with AUC targets. A switch to continuous infusion may therefore improve clinical outcomes in vancomycin-treated critically ill patients