How to Dose Vancomycin in Overweight and Obese Patients with Varying Renal (Dys)function in the Novel Era of AUC 400-600 mg·h/L-Targeted Dosing.

BACKGROUND AND

objectiveThe latest vancomycin guideline recommends area under the curve (AUC)-targeted dosing and monitoring for efficacy and safety. However, guidelines for AUC-targeted starting dosing in patients with obesity and/or renal insufficiency are currently lacking. This study quantifies the pharmacokinetics (PK) of vancomycin in this population and provides AUC-targeted dosing recommendations.

methodsVancomycin concentrations (n = 1188) from therapeutic drug monitoring of 210 overweight and obese patients with varying degrees of renal (dys)function from the ward (74.8%) and intensive care unit (ICU, 25.2%) were pooled with published rich concentration-time data (n = 207) from 20 (morbidly) obese subjects undergoing bariatric surgery. A population model was developed using NONMEM 7.4. Stochastic simulations were performed to design dosing guidelines targeting an AUC

resultsVancomycin clearance (CL) was found to increase linearly with total bodyweight and with renal function (CKD-EPI) in a power relation. Additionally, CL proved 15.5% lower in ICU patients. Our model shows that, to reach the target AUC between 400 and 600 mg·h/L in the first 48 h, two loading doses are required for both continuous infusion and intermittent dosing regimens. Maintenance doses were found to require adjustment for total bodyweight, renal function, and ICU admission status. With this guideline, the median AUC

conclusionsTo achieve safe and effective vancomycin exposure for maintenance doses in overweight and obese patients, renal function, total bodyweight, and ICU admission status should be taken into account.

trial registrationThe AMIGO trial was registered in the Dutch Trial Registry [NTR6058].