Vancomycin target attainment improved following population pharmacokinetic model switch: a large-scale...

The aim of this study was to evaluate the impact of switching population pharmacokinetic models used for model-informed precision dosing (MIPD) of vancomycin on target attainment, acute kidney injury rates, dosing, and sampling burden in 90 295 patients across nineteen hospital systems.

We assessed sites that changed their default vancomycin MIPD model on primary endpoints, including vancomycin area under the concentration-time curve (AUC) target attainment, time to target attainment, and vancomycin-associated AKI rates using an interrupted time series model. Secondary endpoints included vancomycin dosing (day 1 and total course) and sampling frequency. Hospital systems that did not change models served as controls.

In BMI < 40 kg/m² patients, the Goti-to-Thomson model transition significantly improved AUC target attainment on day 1 (+2.1%, P < 0.001), day 2 (+3.1%, P < 0.001), and across the whole treatment course (+2.7%, P < 0.001). Small increases occurred in vancomycin sampling per course (+0.06 samples/course, P < 0.05) and time to target attainment (+0.26 hours, P < 0.05). AUC improvements occurred without statistically significant increases in AKI incidence (KDIGO Stage 1: +0.314%, P > 0.05/3; Stage 2: +0.347%, P > 0.05/3, Stage 3: +0.034%, P > 0.05/3). No significant differences were observed in the BMI ≥ 40 kg/m² or control cohorts.

This large quasi-experimental study shows that switching from one pair of well-validated and highly predictive models to another improves vancomycin target attainment while maintaining low adverse event rates.