A higher dose of vancomycin is needed in critically ill patients with augmented renal clearance

Background: Using standard vancomycin dosage in critically ill patients might lead to therapy failure and worse patient outcomes, augmented renal clearance (ARC) may be the leading risk factor. In this study, we comprehensively investigated the pharmacokinetics-pharmacodynamics (PK-PD) of vancomycin in critically ill patients with ARC, hoping to explore the precise and accurate dose adjustment method for vancomycin. Methods: All critically ill patients tested for steady-state trough vancomycin serum concentrations during the recent 6 years in a tertiary level hospital were collected retrospectively and divided into ARC and non-ARC groups, respectively, according to creatinine clearance (CLcr). Serum vancomycin concentrations were measured by the fluorescence polarization immunoassay method. PK-PD parameters of vancomycin were recorded or calculated. The desired daily dose successful in achieving the lower target trough levels (10 mg/L) of vancomycin were investigated correspondingly. Results: A total of 280 vancomycin concentrations were eligible for analysis. The ARC group (n=139) contained more male patients (64.7%) with average age and CLcr of 40 years old (P<0.05) and 180.8 mL/min (P<0.001), respectively. Those patients exhibited higher clearance (CL) and lower trough serum concentrations than the non-ARC patients under comparable daily doses of vancomycin. All the ICU patients demonstrated lower AUC(24h) values than the target level of 400 mu g.h/mL, and this value showed a lower trend in the ARC group than the non-ARC group (232.9 vs. 316.2 mu g.h/mL). Subtherapeutic trough concentrations of vancomycin (<10.0 mg/L) were observed in 77.7% and 68.8% of the ARC and non-ARC patients (P<0.05). The proportion of patients with a trough concentration of 10-15 and 15-20 mg/L was 17.9% and 4.3%, respectively, in the ARC group and 24.8% and 2.8%, respectively, in the non-ARC group., a daily dose of 46.0 and 35.5 mg/kg of vancomycin is needed, respectively, in the ARC and non-ARC group to achieve a target trough concentration of 10 mg/L. Conclusions: A higher dose of vancomycin is needed in critically ill patients, especially those with ARC, and appropriate TDM-guided dose adjustment should be considered to achieve the targeted therapeutic range and to provide dosing guidance for this: patient population.