Relationship between Vancomycin Area Under the Concentration-Time Curve (AUC) and Nephrotoxicity in Adults

Abstract

Abstract Background While recent data correlate vancomycin’s ratio of the area under the 24 hour time-concentration curve (AUC0−24h) to the pathogen’s minimal inhibitory concentration (MIC) of > 400 mg*hours/L with a favorable clinical outcome, data are sparse to correlate vancomycin AUC0−24h to nephrotoxicity. Our primary objective was to evaluate the relationship between vancomycin AUC0−24h and nephrotoxicity. Methods This single-center, retrospective cohort study was conducted at a large US tertiary-care hospital. Adults hospitalized between 08/01/13 and 08/31/14 with normal baseline renal function receiving intravenous vancomycin ≥ 72 hours were included. Vancomycin AUC0−24h was calculated for each subject utilizing computer-based Bayesian pharmacokinetic methods (BestDose™). Subjects were divided into AUC0−24h of < 700 and > 700 mg*hours/L groups. The primary endpoint of nephrotoxicity (defined as a 50% relative increase or > 0.5 mg/dl absolute increase in SCr over at least 2 consecutive days) was compared between exposure groups. Secondary objectives were to compare the incidence of nephrotoxicity with and without the following risk factors: sepsis, concomitant nephrotoxins, vancomycin troughs > 20 mg/L or doses ≥ 4 g/day, and Charlson Comorbidity Index scores. Results Table 1. Multivariate Model of Nephrotoxicity and Clinical Characteristics Conclusion A significant increase in nephrotoxicity was observed in patients with a vancomycin AUC0−24h ≥ 700 mg*hours/L. Given that this exposure threshold is within the target for efficacy for organisms with elevated MICs, further studies should be conducted to better delineate the AUC0−24h values associated with nephrotoxicity. Disclosures All authors: No reported disclosures.