Retrospective evaluation of a vancomycin dosing bundle in paediatric intensive care

To describe the impact of a real-world, vancomycin dosing bundle ('the bundle'), on vancomycin-associated nephrotoxicity (VAN) rates in critically ill children in a single paediatric intensive care unit (PICU).

A retrospective observational study was conducted in an Australian tertiary PICU from January 2020 to December 2022. The study included all patients who received vancomycin for two or more doses with an associated vancomycin level. During the study period, a staggered implementation was undertaken entailing three interventions on vancomycin prescribing (the bundle): (1) employment of a pharmacist to the PICU, (2) model-informed precision dosing (MIPD), and (2) a reduction in initial vancomycin dosing (15 mg/kg 6 hourly, to 15 mg/kg for the first dose then 10 mg/kg 6 hourly thereafter) alongside a reduction in target trough concentrations from 10-20 to 7-15 mg/L. Data on dosing, vancomycin concentrations, and patient characteristics were collected, and AUC₂₄ was calculated using MIPD software. VAN was defined as a creatinine increase of 0.5 mg/dL or 50% from baseline on two consecutive measurements. Statistical analysis explored associations between time and VAN outcomes.

A total of 648 vancomycin courses were analysed, across 477 unique patients, with a median treatment length of 44.59 h. MIPD represented 18% of the total courses, increasing from 2% to 37% over the study period. VAN occurred in 11.3% of courses, with a consistent rate over the years (13% in 2020, 12% in 2021, and 9% in 2022). Severe VAN rates decreased from 8.6% in 2020 to 3.9% in 2022. The reduction in both severe (P = 0.16) and total (P = 0.4) VAN did not achieve statistical significance.

Implementation of a staggered pharmacist-led vancomycin dosing bundle did not result in a statistically significant reduction in VAN rates over time. However, the observed reduction in severe VAN and associated reduction in AUC₂₄ warrant further investigation with a prospective study design in the high-risk PICU cohort.