Optimization of time to initial vancomycin target trough improves clinical outcomes

Background: Outcomes data for the efficacy of interventions designed to decrease the time to initial target vancomycin troughs are sparse.

Objective: A vancomycin therapeutic drug monitoring (TDM) program was initiated to reduce the time to initial target troughs and to examine the impact on clinical outcomes.

Methods: Single-center, pre- and post-intervention observational study in a 250 bed teaching facility. Adult inpatients treated with physician-guided, vancomycin therapy (historical control, CTRL) were compared to high trough, pharmacist-guided vancomycin therapy (TDM). Nephrotoxicity analyses were conducted to the ensure safety of the TDM. Clinical outcome analysis was limited to patients with normal renal function and culture-confirmed gram positive infections and a pre-defined MRSA subset.

Results: 340 patients met initial inclusion criteria for the nephrotoxicity analysis (TDM, n = 173; CTRL, n = 167). Acute kidney injury occurrence was similar between the CTRL (n = 20) and TDM (n = 23) groups (p = 0.7). Further exclusions yielded 145 patients with gram positive infections for clinical outcomes evaluation (TDM, n = 66; CTRL, n = 75). The time to initial target trough was shorter in the TDM group (3 vs. 5 days, p < 0.001). Patients in the TDM group discharged from the hospital more rapidly, 7 vs. 14 days (Hazards Ratio (HR), 1.41; 95% Confidence Interval [CI] 1.08-1.83; p = 0.01), reached clinical stability faster, 4 vs. 8 days (HR, 1.51; 95% CI 1.08-2.11; p = 0.02), and had shorter courses of vancomycin, 4 vs. 7 days (HR, 1.5; 95% CI 1.15-1.95; p = 0.003). In the MRSA infection subset (TDM, n = 36; CTRL, n = 35), patients in the TDM group discharged from the hospital more rapidly, 7 vs. 16 days (HR, 1.89; 95% CI 1.08-3.3; p = 0.03), reached clinical stability faster, 4 vs. 6 days (HR, 2.69; 95% CI 1.27-5.7; p = 0.01), and had shorter courses of vancomycin, 5 vs. 8 days (HR, 2.52; 95% CI 1.38-4.6; p = 0.003). Attaining initial target troughs in <5 days versus ≥5 days was associated with improved clinical outcomes. All cause in-hospital mortality, and vancomycin treatment failure occurred at comparable rates between groups.

Conclusions: Interventions designed to decrease the time to reach initial target vancomycin troughs can improve clinical outcomes in gram positive infections, and in particular MRSA infections.