Pharmacokinetic/pharmacodynamic parameters of vancomycin for predicting clinical outcome of enterococcal bacteremia

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 (AUC24/MIC) and trough concentration (Ctrough) 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 AUC24/MIC and Ctrough showed fair performance in predicting 30-day mortality (AUC of receiver-operator curve for AUC24/MIC, 0.712; 95% confidence interval [CI] 0.539–0.886; AUC for Ctrough, 0.760; 95% CI 0.627–0.892; pairwise AUC comparison: p = 0.570). Ctrough ≥ 13.94 μg/mL, but not AUC24/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 Ctrough ≥ 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.

Effect of the Minimum Inhibitory Concentration of Vancomycin on the Clinical Outcome ofEnterococcus faeciumBacteremia

“…Patients in Group A (albumin <2.0 mg/dl and MIC ≥1 μg/ml) had a significantly shorter survival time than those in Group B (the rest). From previous studies (9)(10)(11), AUC 24 /MIC, age, and trough VCM levels, have been identified as factors affecting 30-day mortality, but to our knowledge, there have been no previous reports evaluating the impact of nutritional indicators such as albumin on 30-day mortality. These results suggest that in patients with E. faecium bacteremia with MIC ≥1 μg/ml and hypoalbuminemia (albumin <2.0 mg/dl), it is important to provide more focused support, including TDM.…”

“…In this study, we evaluated the effect of MIC on the therapeutic effectiveness and the AUC 24-48 h /MIC on the second day of treatment based on AUC 24-48 h calculated using PAT. Previous studies (9)(10)(11) have included two strains of Enterococcus, E. faecium and E. faecalis, as the target infecting organisms, and there are few reports limited to E. faecium. Therefore, limiting this study to patients with E. faecium bacteremia yields novel findings.…”

Association of Vancomycin AUC/MIC and Trough Concentration With Early Clinical Response in Enterococcus or Coagulase‐Negative Staphylococcus Infection: A Prospective Study

“…and coagulase-negative Staphylococcus (CoNS) 3 despite the high prevalence of serious infections with these bacteria. 6 Previous studies of vancomycin treatment outcomes for Enterococcus indicated that all-cause mortality rates were lower when the AUC 24 /MIC was in the range 389-504, [7][8][9][10] whereas outcomes for C trough were inconclusive. [7][8][9][10][11][12] One study of CoNS infections indicated that AUC/MIC was a suitable index for bacterial killing effect and emergence of vancomycin resistance.…”

“…6 Previous studies of vancomycin treatment outcomes for Enterococcus indicated that all-cause mortality rates were lower when the AUC 24 /MIC was in the range 389-504, [7][8][9][10] whereas outcomes for C trough were inconclusive. [7][8][9][10][11][12] One study of CoNS infections indicated that AUC/MIC was a suitable index for bacterial killing effect and emergence of vancomycin resistance. 13 As these studies were run either retrospectively [7][8][9][10][11][12] or in an animal model, 13 their results may not be directly applicable to patient care.…”

“…[7][8][9][10][11][12] One study of CoNS infections indicated that AUC/MIC was a suitable index for bacterial killing effect and emergence of vancomycin resistance. 13 As these studies were run either retrospectively [7][8][9][10][11][12] or in an animal model, 13 their results may not be directly applicable to patient care. In addition, most of these studies determined the AUC of vancomycin using the default pharmacokinetic model incorporated in the commercial software, [7][8][9][10][11][12] which may not accurately represent the characteristics of their local patient populations and may lead to variability in the calculated AUC.…”