LAUSR

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. 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). 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) 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. Brian S. Metzger, MD, MPH, Allergan (Speaker’s Bureau)Cumberland (Speaker’s Bureau)Melinta (Speaker’s Bureau) Richard L. Hengel, MD, Merck & Co. (Other Financial or Material Support, Grant Steering Committee Member) Kimberly A. Couch, PharmD, MA, FIDSA, FASHP, Allergan (Speaker’s Bureau) Lucinda J. Van Anglen, PharmD, Merck & Co. (Grant/Research Support)