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

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Drug Monitoring

Background:

• Therapeutic drug monitoring (TDM) of vancomycin is crucial due to its narrow therapeutic window.
• Area under the concentration-time curve (AUC) is the gold standard for vancomycin TDM, targeting 400-600 mg*h/L.
• Trough concentrations (Cmin) are often used as a surrogate for AUC, but their accuracy in achieving target AUC is questionable.

Purpose of the Study:

• To evaluate the correlation between vancomycin trough concentrations (Cmin) and area under the curve (AUC) in a large, real-world patient cohort.
• To determine the proportion of patients achieving target vancomycin AUC when only Cmin is considered.
• To assess the reliability of Cmin as a proxy for vancomycin AUC.

Main Methods:

• A retrospective analysis of anonymized data from 17,711 adult patients treated with vancomycin in 2021-2022.
• Vancomycin AUC was calculated using a Bayesian method with 4 validated models.
• Paired Cmin and AUC data were categorized as low, target, or high based on established therapeutic ranges.

Main Results:

• A significant categorical disagreement (34.3%) was observed between Cmin and AUC.
• Most discrepancies (30%) occurred with low Cmin but target AUC.
• Only 23% of paired Cmin and AUC measurements fell within the target therapeutic ranges, highlighting AUC variability across Cmin categories.

Conclusions:

• Current vancomycin TDM practices relying solely on Cmin are inadequate for ensuring target AUC attainment.
• Direct calculation of vancomycin AUC is recommended for precise therapeutic drug monitoring.
• These findings support a shift towards AUC-based vancomycin monitoring to optimize efficacy and safety.