Big Data Bayesian Truths: No Vancomycin Trough Concentration Target Is Sufficiently Precise for Safety or Efficacy.

Abstract

Introduction: Therapeutic drug monitoring is standard of care for vancomycin because of the known efficacy and safety exposure window (ie, area under the concentration-time curve [AUC] of 400-600 mg × 24 hours/L). Despite guideline recommendations, AUCs are infrequently calculated because of the perceived adequacy of trough (Cmin) concentrations. Yet, the percentage of real-world patients with goal measured vancomycin trough concentrations that achieve target vancomycin AUC remains unknown.

Methods: A large cohort of internationally represented adult patients treated with vancomycin in 2021 and 2022 and therapeutic drug monitoring performed had data anonymized via an electronic clearinghouse at DoseMe. Unique patients, dosing events, and measured Cmin were identified. Patient-individualized AUC was calculated using a Bayesian method with 4 validated models. For each dosing event, Cmin and AUC pairs were compared and categorized as "low," "target," and "high" using the therapeutic ranges for Cmin of 15-20 mg/L and AUC of 400-600 mg × 24 hours/L.

Results: In 2022, 17,711 adult patients from the European Union (4.9%), Australia (4.0%), and the United States (91.1%) had 26 769 measured trough levels obtained. Categorical disagreement between Cmin and AUC was 34.3%, with most disagreement (7959 Cmin levels, 30%) occurring with low Cmin but target AUC. Only 23% of paired Cmin and AUC were within range. AUC was variable for all trough categories (ie, low, target, and high).

Conclusions: These findings support AUC therapeutic drug monitoring and challenge Cmin as an adequate vancomycin AUC proxy. Because no trough concentration or range was sufficiently precise to ensure AUC targets, we suggest direct calculation of AUC.