vanA-consistent phenotype vancomycin-resistant enterococcal colonization is associated with inferior overall survival in acute myeloid leukemia patients undergoing intensive chemotherapy: a single-center retrospective study

BACKGROUND: Vancomycin-resistant enterococci (VRE) colonization is common among patients with acute myeloid leukemia (AML) undergoing intensive chemotherapy. Whether the teicoplanin-defined VRE phenotype, specifically vanA-consistent (teicoplanin-resistant) versus vanB-consistent (teicoplanin-susceptible), is associated with adverse outcomes is unknown. METHODS: We conducted a retrospective single-center cohort study of 192 VRE-colonized AML patients who received intensive induction chemotherapy between 2015 and 2024. vanA-consistent phenotype (n = 35, 18.2%) was defined as VRE isolates demonstrating vancomycin (MIC > 4 mg/l) and teicoplanin resistance (MIC > 2 mg/L). vanB-consistent phenotype (n = 157, 81.8%) was defined as VRE isolates susceptible to teicoplanin. The primary endpoint was overall survival (OS). Cox proportional hazards regression estimated the association between VRE phenotype and OS with adjustment for ELN 2022 genetic risk, sex, ECOG performance status, and allogeneic stem cell transplantation. Healthcare-exposure variables were compared between phenotypes, and the interaction between vanA-consistent phenotype and cumulative inpatient days before VRE detection was evaluated. RESULTS : vanA-consistent phenotype patients had significantly inferior OS compared with vanB-consistent phenotype patients (3-year OS 46.1% vs. 73.2%; log-rank p = 0.004). vanA-consistent phenotype was strongly associated with adverse-risk ELN 2022 genetics (54% vs. 24%; OR 3.69, p < 0.001). Despite this association, vanA-consistent phenotype remained associated with OS after adjustment for ELN 2022 risk, sex, ECOG, and allo-SCT (HR 1.85, 95% CI 1.03-3.34, p = 0.041). The vanA-associated hazard increased with longer cumulative inpatient exposure before VRE detection. No significant differences were observed for infection-related complications between vanA- and vanB-consistent phenotypes. CONCLUSIONS : vanA-consistent phenotype VRE colonization is an adverse prognostic factor in VRE-colonized AML patients, providing prognostic information beyond ELN 2022 genetic risk classification. To our knowledge, this is the first study to demonstrate differential outcomes by teicoplanin-defined VRE phenotype. Despite enrichment for adverse-risk genetics in vanA-consistent phenotype patients, this did not fully account for the survival disadvantage. Prospective multicenter validation is warranted.