Impact of a vancomycin loading dose on the achievement of target vancomycin exposure in the first 24 h and on the accompanying risk of nephrotoxicity in critically ill patients

C. J. Hodiamont, N. P. Juffermans, S. E. Berends, D. J. van Vessem, N. Hakkens, R. A. A. Mathôt, M. D. de Jong, R. M. van Hest

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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 languageEnglish
Pages (from-to)2941-2949
Number of pages9
JournalJournal of antimicrobial chemotherapy
Volume76
Issue number11
DOIs
Publication statusPublished - 1 Nov 2021

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