Practical dose ranges supporting target vancomycin exposure with AUC-guided dosing in overweight and obese patients:...

Evidence supporting area under the concentration-time curve (AUC)-guided vancomycin dosing in overweight and obese patients remains limited. This multicentre retrospective study aimed to identify pragmatic loading dose (LD) and maintenance dose (MD) ranges associated with target AUC attainment in this population.

Patients aged ≥15 years with a body mass index (BMI) ≥ 25 kg/m² who received vancomycin for ≥3 days and had ≥2 trough concentration measurements were included from four Japanese hospitals (2012-2025). AUC_0-24 and steady-state AUC₂₄ (AUC_ss) were estimated using Bayesian software. Multivariate logistic regression analyses identified factors associated with achieving target AUCs (AUC_0-24: 400-500 μg·h/mL; AUC_ss: 400-600 μg·h/mL).

Among 209 patients (median BMI 27.2 kg/m²), LD was independently associated with attainment of target AUC_0-24 (OR 1.08, 95% CI 1.02-1.15). An LD of approximately 20 mg/kg was associated with early target exposure. For maintenance therapy, estimated glomerular filtration rate (eGFR) and MD were independently associated with AUC_ss attainment (OR 0.979, 95% CI 0.964-0.995, p = 0.008; OR 1.050, 95% CI 1.010-1.090, p = 0.018, respectively). Pragmatic interim MD ranges were approximately 9.2, 16.2 and 26.3 mg/kg/day for patients with eGFR<30, 30-60 and >60 mL/min/1.73 m², respectively.

In this multicentre real-world cohort of overweight/obese adults, an LD around 20 mg/kg (ceiling 2 g) was associated with early AUC_0-24 target attainment. MD and renal function were independent predictors of AUC_ss, informing interim renal-stratified MD ranges until TDM results become available. Early TDM remains essential given significant inter-individual variability.