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

• Published in: Clinical pharmacokinetics Vol. 63; no. 1; pp. 79 - 91
• Main Authors: Zhang, Tan, Krekels, Elke H. J., Smit, Cornelis, van Dongen, Eric P. A., Brüggemann, Roger J. M., Knibbe, Catherijne A. J.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.01.2024; Springer Nature B.V
• Subjects: Anti-Bacterial Agents - pharmacokinetics; Antibiotics; Area Under Curve; Body mass index; Clinical medicine; Datasets; Drug dosages; Gastrointestinal surgery; Gram-positive bacteria; Humans; Internal Medicine; Kidney; Medicine; Medicine & Public Health; NTR; NTR6058; Obesity; Obesity - complications; Obesity - drug therapy; Original; Original Research Article; Overweight; Overweight - complications; Overweight - drug therapy; Patients; Pharmacokinetics; Pharmacology/Toxicology; Pharmacotherapy; Staphylococcus infections; Therapeutic drug monitoring; Vancomycin - pharmacokinetics; United States > US
• ISSN: 0312-5963; 1179-1926; 1179-1926
• DOI: 10.1007/s40262-023-01324-5

Background and Objective The 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. Methods Vancomycin 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 24 between 400–600 mg·h/L. Results Vancomycin 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 24 is well within the target from the start of the treatment onwards. Conclusions To 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 Registration The AMIGO trial was registered in the Dutch Trial Registry [NTR6058].