The Impact of Vancomycin Area Under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity: a Quasi-Experiment

Background: Evidence suggests maintaining vancomycin trough concentrations between 15 and 20 mg/L, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC 24h ) target of ≥ 400 mg*h/L. Many patients with trough concentrations in this range have AUC 24h in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. Based on this, the Detroit Medical Center switched from trough concentration to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity. Methods: Single center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by AUC 24h versus trough concentration. Multivariable logistic and Cox-proportional hazard regression examined the independent association between monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Results: Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity in both logistic regression (OR, 0.52; 95% CI, 0.34-0.80; P =0.003) and Cox-proportional hazards regression (HR, 0.53; 95% CI, 0.35-0.78; P =0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Conclusion: Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity which appears to be a result of reduced vancomycin exposure.