1391. Vancomycin Area Under the Curve (AUC) to Predict Nephrotoxicity: A Systematic Review and Meta-Analysis of Observational Studies

Background Recent studies have proposed monitoring vancomycin area under the curve (AUC) as a more precise method of attaining goal exposures compared with trough monitoring. Different dosing methods and different exposure-toxicity thresholds have been proposed. Therefore, we aimed to analyze the relationship between vancomycin AUC and nephrotoxicity reported across recent studies. Methods A systematic review of Pubmed, Medline, Scopus and compiled references was conducted. We included randomized, cohorts and case–control studies that reported vancomycin AUCs and risk of nephrotoxicity from (January 1, 1990 to January 31, 2018). The primary outcome was nephrotoxicity, defined as an increase in serum creatinine of ≥0.5 mg/L or a 50% increase from baseline on two or more consecutive measurements. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Subset analyses were conducted when possible on the impact of AUC0-24 hours and AUC24-48 hoursr exposures and AUC vs. trough guided dosing on the outcome of nephrotoxicity. AUC nephrotoxicity thresholds ranged between 550 and 700 mg hour/L. We grouped values according to lower (i.e., <650) or higher average AUC, with a threshold value of ≥650 mg hour/L defining higher AUC based on a recent prospective trial. Results We identified eight eligible observational studies with a total of 2,491 patients. Of those, five studies reported AUC0-24 associated with nephrotoxicity, two studies reported AUC24-48, and two studies reported nephrotoxicity associated with AUC vs. trough-guided dosing. No RCTs were identified. Lower AUC0-24 values were associated with significantly reduced risk of nephrotoxicity (OR 0.36, 95% CI 0.23–0.56). In a sub-analysis of two studies, AUC24-48<650 mg hour/L was associated with significantly lower risk of nephrotoxicity (OR 0.45, 95% CI 0.27–0.75). Nephrotoxicity associated with AUC-guided dosing was significantly lower than trough-guided dosing (OR 0.68, 95% CI 0.46–0.99). Conclusion This meta-analysis suggests that AUC0-24 lower than 650 mg hour/L may result in a decreased risk of nephrotoxicity. AUC-guided vancomycin dosing may result in less vancomycin-associated nephrotoxicity. Additional investigations into the benefit of AUC-guided dosing are warranted. Disclosures All authors: No reported disclosures.