Impact of model‐informed precision dosing on achievement of vancomycin exposure targets in pediatric patients with cystic fibrosis.

Background: Vancomycin is commonly used to treat acute pulmonary exacerbations in pediatric patients with cystic fibrosis (CF) and a history of methicillin‐resistant Staphylococcus aureus. Optimizing vancomycin exposure during therapy is essential and area under‐the‐curve (AUC)‐guided dosing is now recommended. Model‐informed precision dosing (MIPD) utilizing Bayesian forecasting is a powerful approach that can support AUC‐guided dose individualization. The objective of the current study was to examine the impact of implementing an AUC‐guided dose individualization approach supported via a MIPD clinical decision support (CDS) tool on vancomycin exposure, target attainment rate, and safety in pediatric patients with CF treated with vancomycin during clinical care. Methods: A retrospective chart review was performed in patients with CF at a single children's hospital comparing pre‐ and post‐implementation of a MIPD approach for vancomycin supported by a cloud‐based, CDS tool integrated into the electronic health record (EHR). In the pre‐MIPD period, vancomycin starting doses of 60 mg/kg/day (<13 years) or 45 mg/kg/day (≥13 years) were used. Dose adjustment was guided by therapeutic drug monitoring (TDM) with a target trough 10–20 mg/L. In the post‐MIPD period, starting dose and dose adjustment were based on the MIPD CDS tool predictions with a target 24 h AUC (AUC24) 400–600 mg*h/L. Exposure and target achievement rates were retrospectively calculated and compared. Rates of acute kidney injury (AKI) were also compared. Results: Overall, 23 patient courses were included in the pre‐MIPD period and 21 patient courses in the post‐MIPD period. In the post‐MIPD period, an individualized MIPD starting dose resulted in 71% of patients achieving target AUC24 compared to 39% in the pre‐MIPD period (p < 0.05). After the first TDM and dose adjustment, target AUC24 achievement was also higher post‐MIPD versus pre‐MIPD (86% vs. 57%; p < 0.05). AKI rates were low and similar between periods (pre‐MIPD 8.7% vs. post‐MIPD 9.5%; p = 0.9). Conclusion: An MIPD approach implemented within a cloud‐based, EHR‐integrated CDS tool safely supported vancomycin AUC‐guided dosing and resulted in high rates of target achievement. [ABSTRACT FROM AUTHOR]