P-1242. Missing big in our little patients: Vancomycin trough concentrations do not predict IDSA guideline targeted AUCs
Authors: Scheetz Marc H , Shiau Justin , Sabourenkov Paul , Roy Sharmeen 
Published: January 2025

Abstract

Background
Therapeutic drug monitoring is the guideline-recommended, standard of care for vancomycin because of the known efficacy and safety exposure window [i.e. area under the concentration curve (AUC) of 400-600 mg*24hours/L]. Yet, surveys show that few practitioners calculate AUCs because of the perceived adequacy of trough concentrations; however, the percentage of real-world pediatric patients with goal vancomycin trough concentrations that achieve target vancomycin AUC remains unknown. Thus, we queried a large cohort of internationally represented, real-world, pediatric patients with precise estimates of vancomycin AUC exposures and measured trough concentrations.

Methods
Pediatric patients treated with vancomycin between 2023-2024 and with therapeutic drug monitoring (TDM) performed had data anonymized via an electronic clearinghouse. Unique patients and dosing events were quantified; trough concentrations within 2 hours of the next dose were identified, and patient individualized AUC was calculated using a Bayesian method with 2 validated models. For each dosing event, pairs of trough and AUC24 were compared and categorically classified as “low”, “target”, and “high” according to trough and AUC (i.e. 15-20 mg/L and 400-600 mg*24hours/L, respectively). Prediction intervals (90%PI) were calculated.
Figure 1. Categorical agreement of troughs and AUC between "low, in range, and high"

Results
A total of 1,394 pediatric patients from the United States (72%), Australia (17%), and the European Union (11%) with 2,563 dosing events with paired trough and AUC were included (Table 1). Categorical disagreement between trough and AUC was 37%, most disagreement (2,563 dosing events, 21.2%) occurred at low trough but AUC at target. Only 24.5% of paired trough and AUC were simultaneously at target. AUC was highly variable for all trough categories (i.e. low, target, and high, Figs. 1,2). Troughs of 15 and 20mg/L resulted in a AUCs with 90%PIs of 334-725 and 419-811 mg*24hours/L (Fig. 3), respectively.
Figure 2. Scatterplot of trough by AUC with categorization overlaid

Conclusion
Trough concentrations resulted in frequent misclassification of AUC category, with troughs&lt; 15 mg/L frequently resulting in AUCs &gt;400 mg*24h/L. These findings are important as low troughs result in additional unnecessary sampling, compel clinicians to increase doses, and lead to unintended high AUCs. Importantly, high AUCs cause increased kidney injury.

Prediction interval for AUC at any given trough

Disclosures
Marc H. Scheetz, PharmD, MSc, Abbvie: Advisor/Consultant|Basilea: Advisor/Consultant|Cidara: Advisor/Consultant|DoseMe: Advisor/Consultant|Entasis: Advisor/Consultant|F2G: Advisor/Consultant|GSK: Advisor/Consultant|Lykos: Advisor/Consultant|Roche: Advisor/Consultant|Third Pole Therapeutics: Advisor/Consultant|Xelia: Advisor/Consultant Paul Sabourenkov, MSc(Adv)Bioinf, DoseMe Pty Ltd: Employee Sharmeen Roy, PharmD, BCPS, DoseMe: Employee