Abstract
PURPOSE: To find pharmacokinetic/pharmacodynamic parameters of vancomycin associated with the optimal outcome of severe infection due to Enterococcus species. METHODS: We retrospectively reviewed enterococcal bacteremia cases treated with vancomycin from January 2015 to December 2020. The primary outcome was 30-day mortality. We calculated cutoff values of the ratio of vancomycin area under the concentration-time curve over 24 h to the minimum inhibitory concentration (AUC(24)/MIC) and trough concentration (C(trough)) during the initial 72 h of treatment. The optimal cutoff value was determined using the Youden index. Binary variables created based on these cutoffs were further assessed using multivariable analysis. RESULTS: A total of 65 patients were included. The majority (87.7%) had solid or hematologic malignancies. Thirty-day mortality and nephrotoxicity occurred in nine (13.4%) and 14 (21.5%) patients, respectively. Both vancomycin AUC(24)/MIC and C(trough) showed fair performance in predicting 30-day mortality (AUC of receiver-operator curve for AUC(24)/MIC, 0.712; 95% confidence interval [CI] 0.539-0.886; AUC for C(trough), 0.760; 95% CI 0.627-0.892; pairwise AUC comparison: p = 0.570). C(trough) ≥ 13.94 μg/mL, but not AUC(24)/MIC ≥ 504, had a significant association with 30-day mortality after adjusting for confounders (odds ratio, 8.40; 95% CI 1.60-86.62; p = 0.010). CONCLUSION: Mean C(trough) ≥ 13.94 μg/mL during the initial 72 h was associated with higher 30-day mortality in enterococcal bacteremia. Further studies are warranted to elucidate optimal pharmacokinetic targets for enterococcal bacteremia.