Predictive performance of an antibiotic precision dosing software program in critically ill adults with infection

Critically ill patients exhibit altered pharmacokinetics, rendering antibiotic dosing challenging. Achieving therapeutic antibiotic exposures may be improved with the use of precision dosing software programs.

To quantify and compare both a priori and a posteriori predictive performance of an antibiotic precision dosing software program in a heterogenous cohort of critically ill adults with infection.

The precision dosing program, ID-ODSTM, was used to predict a priori and a posteriori concentrations for piperacillin, meropenem, cefepime, flucloxacillin and vancomycin using clinical and demographic data derived from a previous study in critically ill adults (GUIDE trial). Predicted concentrations were compared to observed concentrations using pre-specified acceptance criteria (median predictive error (MDPE) ≤20% and median absolute predictive error (MDAPE) ≤30%), along with F20 and F30 metrics. Furthermore, the impact of predictions on theoretical dosing recommendations to achieve pre-defined drug exposures was assessed.

The a priori predictive performance in 81 patients administered beta-lactams did not meet any pre-specified acceptance criteria (pooled MDPE -35% and MDAPE 58%). However, all beta-lactams met accuracy acceptance criteria for the a posteriori approach (pooled MDPE -3.6%), although only cefepime demonstrated acceptable precision and F20 and F30 acceptance. In 25 patients administered vancomycin, a priori predictive performance met all acceptance criteria for accuracy and precision.When assessing a priori theoretical dosing recommendation concordance, approximately one in three predictions led to an unnecessary dosing action. Concordance was similar with an a posteriori approach, however, overprediction was observed in 20% of meropenem predictions.

In a heterogenous adult ICU population, the a priori predictive performance of vancomycin was shown to be acceptable. Conversely, the a priori predictive performance for the beta-lactams was not acceptable. Although predictive performance improved with the a posteriori approach for beta-lactams, only cefepime met acceptance criteria.