VANCOmycin dose adjustments comparing trough levels to the ratio of the area under de curve to the minimum inhibitory concentration method using a BAYESian approach: A feasibility study.

Abstract

WHAT IS KNOWN AND OBJECTIVE?: The latest published guidelines advocate for the area under the concentration-time curve to minimal inhibitory concentration (AUC0-24h /MIC) estimated with bayesian calculations. This recommended pharmacokinetic monitoring transition is not based on randomized controlled prospective data. METHODS: In this open-label feasibility RCT, patients were assigned to have their vancomycin dosing adjusted based on bayesian-guided AUC0-24h /MIC or trough levels. Primary outcomes were consent rate, number of patients recruited per month, compliance with blood sampling schedule and compliance with bayesian software recommendations. Secondary outcomes focused on target attainment, safety and operational impacts. RESULTS AND DISCUSSION: Forty-five patients underwent randomization (23 bayesian, 22 trough). Consent rate was 37,5% for an average of 9.8 patients recruited per month meeting pre-specified objectives of 30% (p= 0.073) and 10 (p= 0.74) respectively. A 74.8% compliance with blood sampling schedule was below the pre-specified objective of 80% (p= 0.038). There was no statistically significant difference between the 83.7% compliance with bayesian software recommendations and the pre-specified objective of 90% (p= 0.21). Although exploratory, key clinical results were significant increases in the bayesian group for proportion of levels at target (RR 1.32; 95% CI 1.01-1.72; P=0.038), number of blood samplings for patients (p= 0.036) and pharmacists' time spent on monitoring (p< 0.0001). A tendency towards a reduced incidence of nephrotoxicity in the Bayesian group was observed (RR 0.57; 95% CI 0.16-2.12; p= 0.46). WHAT IS NEW AND CONCLUSIONS?: This trial demonstrates that it would be feasible to conduct a properly sized RCT comparing vancomycin Bayesian-guided AUC0-24h /MIC to trough level monitoring. Although exploratory, this trial also showed a tendency towards reduced incidence of nephrotoxicity and an increased proportion of dosages at therapeutic targets with Bayesian monitoring.