Abstract
Background: The advocated pharmacokinetic/pharmacodynamic (PK/PD) target for vancomycin, AUC/MIC≥400 mg·h/L, may not be reached with a conventional fixed starting dose of 1000 mg in critically ill patients, but increasing the dose may cause nephrotoxicity. Objectives: To evaluate the effect of a weight-based loading dose of 25 mg/kg vancomycin on PK/PD target attainment in the first 24 h (AUC0-24) in critically ill patients and to evaluate whether this increases the risk of acute kidney injury (AKI). Patients and methods: A prospective observational before/after study was performed in ICU patients, comparing the percentage of vancomycin courses with AUC0-24≥400 mg·h/L and the incidence of AKI, defined as worsening of the risk, injury, failure, loss of kidney function and end-stage kidney disease (RIFLE) score. The conventional dose group received 1000 mg of vancomycin as initial dose; the loading dose group received a weight-based loading dose of 25 mg/kg. A population PK model developed using non-linear mixed-effects modelling was used to estimate AUC0-24 in all patients. Results: One hundred and four courses from 82 patients were included. With a loading dose, the percentage of courses achieving AUC0-24≥400 mg·h/L increased significantly from 53.8% to 88.0% (P=0.0006). The percentage of patients with new-onset AKI was not significantly higher when receiving a 25 mg/kg loading dose (28.6% versus 37.8%; P=0.48). However, the risk of AKI was significantly higher in patients achieving AUC0-24>400 mg·h/L compared with patients achieving AUC<400 mg·h/L (39.0% versus 14.8%; P=0.031). Conclusions: A weight-based loading dose of 25 mg/kg vancomycin led to significantly more patients achieving AUC0-24≥400 mg·h/L without increased risk of AKI. However, some harm cannot be ruled out since higher exposure was associated with increased risk of AKI.
Original language | English |
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Pages (from-to) | 2941-2949 |
Number of pages | 9 |
Journal | Journal of antimicrobial chemotherapy |
Volume | 76 |
Issue number | 11 |
DOIs | |
Publication status | Published - 1 Nov 2021 |