Association of vancomycin trough levels, AUC and AUC/MIC ratios with clinical outcomes in patients with enterococcal bacteremia: a prospective cohort study

Sel E. K., Tufan B., Atagun G. K., Oguz V., Ozbek Ö. A., Gumustekin M., ...Daha Fazla

BMC INFECTIOUS DISEASES, cilt.25, sa.1, 2025 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 25 Sayı: 1
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1186/s12879-025-11400-9
  • Dergi Adı: BMC INFECTIOUS DISEASES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CINAHL, EMBASE, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: Vancomycin, Enterococcus bacteremia, Serum trough level, Area under the curve/Minimum inhibitory concentration, AUC/MIC
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Background The optimal vancomycin pharmacokinetic/pharmacodynamic (PK/PD) targets for successful treatment of enterococcal infections remain controversial. To clarify these targets, this study investigated the association of the vancomycin area under the curve (AUC), the AUC/minimum inhibitory concentration (MIC) ratio, and the serum trough concentration (C-trough) with clinical outcomes (treatment efficacy, safety, and 30-day mortality) in adult patients with enterococcal bacteremia. Methods This prospective cohort study was conducted at a tertiary university hospital between January 2023-2025 and included adult patients with enterococcal bacteremia who were treated with vancomycin and met predefined inclusion/exclusion criteria. Data were prospectively collected. The associations of the steady-state 24-hour vancomycin AUC (AUC(ss)), the AUC(ss)/MIC ratio, and the trough concentration (Ctrough-ss) with treatment efficacy, safety, and 30-day mortality were evaluated. Bayesian modeling was used to estimate the AUC. Optimal vancomycin PK/PD cutoff values were determined using receiver operating characteristic (ROC) curve analysis. Results Among the 53 patients included in the study, treatment was effective in 62.3%, while acute kidney injury (AKI) developed in 47.2%. The 30-day all-cause mortality rate was 28.3%. Regarding treatment efficacy, only the AUC(ss) cutoff value was found to be statistically significant; patients with AUC(ss)<616 gh/mL had a higher rate of efficacy compared to those with AUC(ss)>= 616 mu gh/mL (p = 0.031). A similar pattern was observed for mortality at this cutoff value (p = 0.041). The highest efficacy was observed in the 400-616 mu gh/mL range (18 out of 22 patients, 82%). The cutoff values for AKI were determined to be 538 mu gh/mL for AUC(ss) and 15.7 mu g/mL for Ctrough-ss. Acute kidney injury occurred in 68.8% of patients with AUC(ss)>= 538 mu gh/mL and in 14.3% of those with AUC(ss)<538 gh/mL (p < 0.001). Similarly, the risk of AKI was significantly greater in patients with Ctrough-ss >= 15.7 g/mL than in those with Ctrough-ss<15.7 g/mL (p < 0.001). Conclusions In patients with enterococcal bacteremia treated with vancomycin, adjusting the dose to achieve an AUC(ss) between 400 and 616 gh/mL may be appropriate to ensure effective therapy. However, due to the risk of AKI at these doses, patients should be closely monitored. For safe treatment in cases where AUC monitoring is not feasible, maintaining a serum Ctrough-ss below 15.7 mu g/mL may be appropriate.