Precision Dosing of Vancomycin in Critically Ill Children

A Multicentric, Randomised Controlled Clinical Trial to Study the Impact of Bedside Model-informed Precision Dosing of Vancomycin in Critically Ill Children

The overall objective of this project is to investigate the large-scale utility of MIPD of vancomycin at point-of-care in ICU children. This evaluation includes a comparison with the more standard approach on Clinical and patient-oriented measures.

Vancomycin is an antibiotic with a narrow therapeutic-toxic margin. This means that the minimum and maximum target blood target levels differ little from each other. Too low concentrations will reduce the effect of the antibiotic; higher concentrations may result in serious side effects, including renal toxicity. Vancomycin dosing tailored to the critically ill child is challenging.

Currently, the starting dose of vancomycin is calculated on a milligram per kilogram basis, which is the same for all patients. The dose is then adjusted based on a measured vancomycin blood concentration (if too high or too low). Despite this measurement, quickly achieving target concentrations remains a major challenge.

This multicenter, individual randomized study investigates the added value of a user-friendly computer program for calculating the vancomycin dose in critically ill children, compared to the current standard-of-care. Specifically, the investigators will study whether the use of this computer program leads to a shorter time to reach target concentrations, a reduction in the number and severity of side effects on the kidney, a reduction in patient burden, and a reduction in time to cure and duration of hospitalization.

Inclusion Criteria:

• age: 0-18 years
• admitted to ICU or PHO unit
• suspected or confirmed Gram positive infection
• planned to start on intravenous intermittent or continuous infusion vancomycin treatment
• informed consent signed by parents or legal representatives
• not previously enrolled in this trial

Exclusion Criteria:

• extracorporeal treatment at inclusion or started during treatment (extracorporeal membrane oxygenation, dialysis, body cooling)
• n or p RIFLE category failure at inclusion (Day 0) (see section 8.1.2. screening)
• Known chronic kidney disease as defined by the KDIGO definition as: structural or functional abnormalities of the kidney regardless of GFR for < 3 months or GFR < 60ml/min/1.73m² for ≥ 3 months. eGFR is estimated using the modified Schwartz equation
• patient death is deemed imminent and inevitable