1327 - Vancomycin Dosing by AUC₂₄/MIC in Comparison to Traditional Trough Dosing in Office Infusion Centers (OICs)

Background: New vancomycin (VAN) guidelines have been published, with recommendations that dosing in patients (pts) with methicillin-resistant S. aureus (MRSA) infections be guided by VAN area under the concentration-time curve from 0 to 24 h to MIC ratio (AUC₂₄).  The guidelines emphasize daily AUC₂₄ values should be between 400-600 mg*h/L to maximize efficacy and minimize likelihood of acute kidney injury (AKI). Our physicians and clinical pharmacists currently use trough levels to manage outpatient VAN dosing with a general target of 15-20 mg/L. The current pharmacokinetic (PK) model provides an option for dosing using trough or calculated AUC₂₄.

Methods: We identified pts receiving VAN for S. aureus infections (default MIC of 1 mg/mL) from 2018-2020. We conducted a PK evaluation of pts with ≥1 trough level and compared it to model predicted AUC₂₄. Data collected included pt characteristics, VAN regimen, trough concentrations, PK evaluation, and AKI, defined as a 50% decrease in CrCL from baseline. A Bayesian PK model was used to calculate predicted dosing based upon trough concentrations (DoseMeRx^®, Moorestown, NJ).

Results: 100 pts (mean age: 61±15 yrs, 62% male) from 6 OICs were included, with 82% treated for MRSA and 18% for methicillin-sensitive S. aureus infection. Mean initial dose of VAN in the OIC was 2.6±1 g/d in divided doses, most frequently every 12 hrs (68%). Median duration of outpatient therapy was 28 days [IQR, 16-36]. 69% received VAN in the hospital prior to the OIC.  100 pts had 239 trough levels with a corresponding PK analysis. Mean trough levels were 17.1±6.4 mg/L. Mean corresponding AUC₂₄ was 498±98 mg*h/L. The relationship between trough and AUC₂₄ is shown in Fig 1. 25 evaluations indicated an AUC₂₄ < 400, with 8 (32%) resulting in a dose increase.  13 evaluations indicated AUC₂₄ > 600, with 6 (46%) resulting in a subsequent dose decrease. 4 pts developed reversible AKI, all with AUC₂₄ > 540. Use of AUC₂₄ for dosing provided opportunities to adjust dosing in 38/239 evaluations (16%).Figure 1. Relationship between Trough and AUC24 (n=239)


Conclusion: This PK evaluation showed a correlation between trough levels and AUC₂₄ with opportunities for VAN dose adjustment using AUC₂₄, and to identify pts at risk for developing AKI.  Dosing with AUC₂₄ is particularly useful in the outpatient setting in which true trough evaluations can be difficult to obtain.