Role of Vancomycin Area Under the Curve Trapezoidal Dosing in Prevention of Nephrotoxicity as Compared with Traditional Trough-based Dosing

Background: Vancomycin is a fundamental treatment for resistant grampositive infections and is implicated in vancomycin-induced-nephrotoxicity (VIN) at high concentrations. Troughs greater than 18 mcg/ml are associated with a 4-fold increase in nephrotoxicity. Additionally, Area Under the Curve/ Minimum Inhibitory Concentration (AUC/MIC) levels over 600 mg*h/L are implicated in VIN. It is proposed that trapezoidal AUC/MIC dosing strategies reduce VIN instances. Materials and Methods: Patients greater than 18 years of age who received 72 hr of vancomycin therapy for a non-skin or soft-tissue or urinary indication were included in this retrospective cohort study. The primary endpoint was rate of nephrotoxicity based on the Acute Kidney Injury Network (AKIN) criteria for those patients who suffered an increase in serum creatinine of 0.3 mg/dl or greater after 48 hr of vancomycin therapy. The secondary endpoints were mean 24-hr vancomycin daily doses and instances of trough excursions above 18 mcg/ mL between groups. Forty patients met inclusion criteria for the AUC/MIC arm while seventy-nine met inclusion to the trough arm. Results: Rates of nephrotoxicity in the trough versus AUC/MIC were 36 patients (30.3%) and 3 patients (7.5%) respectively with a p<0.001. AUC/MIC based dosing was associated with decreased rates of nephrotoxicity and decreased rates of trough excursions above 18 mcg/ml. Conclusion: The AUC/MIC dosing strategy was associated with lower rates of VIN compared with troughbased dosing.