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.