A Quasi-Experimental Evaluation of Single Trough-Based Area Under the Curve Guided Dosing on the Incidence of Vancomycin Associated Nephrotoxicity in Veteran Patients

Abstract

Background: Two common dosing strategies for vancomycin are trough-based and area under the curve (AUC)-based dosing. Objective: To compare the incidence of nephrotoxicity in trough-based dosing group with the single trough-based AUC dosing at the Salem VA Medical Center. Methods: This retrospective study included patients who received trough-based dosing of vancomycin between January 1, 2017, and January 1, 2019 (preimplementation group) and AUC-based dosing (postimplementation) between October 1, 2019, and October 1, 2021, at the Salem VA Medical Center. The primary outcome was nephrotoxicity at 96 hours, 7 days, and entire hospital length of stay (LOS). Secondary outcomes included 30-day readmission and all-cause mortality rates, cumulative doses at 24, 48, and 72 hours, and percentage of patients considered at goal (AUC 400-600 or trough between 10 and 20 mg/L). Propensity score (PS) matching was utilized to adjust for confounding. Results: After PS matching 100 patients were included in preimplementation and 95 patients in the postimplementation group. The average study patient was a 68-year-old white male. There was significant reduction in the risk of nephrotoxicity in postimplementation cohort at 96 hours (adjusted (a)HR: 0.28, 95% CI (0.12-0.66); 7 days (aHR: 0.39, 95% CI (0.18-0.85); and entire hospital LOS (aHR: 0.46, 95% CI (0.22-0.95). Secondary outcomes showed no difference between the groups except significantly higher proportion of patients were considered at therapeutic goal in the postimplementation cohort compared with pre-implementation cohort. Conclusion: This hypothesis generating study shows that AUC-based dosing calculated using single trough concentration may result in reduced rate of nephrotoxicity than trough-based dosing.

Keywords: AUC; nephrotoxicity; rough concentration; vancomycin; veterans.

Figure 1.

Patient selection flowchart. Please note that patients were initially pulled using Structured Query language (SQL) and excluded based on the initial exclusions such as number of vancomycin doses, if they received dialysis during the hospital stay, if no trough level was available, or if patients had duplicate entry due to change in their wards, that is, step down from ICU to medical floors. After which 139 eligible patients from the post-implementation cohort were matched 1:1 using PS as described in the methods section of the manuscript resulting in 131 matched patients in each cohort Due to the limitation of SQL and Electronic medical records, manual review of charts resulted in additional exclusion criteria resulting in total of 95 patients in post-implementation cohort and 100 patients in pre-implementation cohort. Abbreviation: PS, Propensity Score.

Figure 2.

(a) Time to nephrotoxicity at 96 hours. (b) Time to nephrotoxicity at 7 days. (c) Time to nephrotoxicity for hospital LOS. Abbreviation: LOS, length of stay.