BackgroundNeutropenic children with hematological diseases were associated with higher morbidity of carbapenem-resistant enterobacteriaceae (CRE) blood-stream infection (BSI) or colonization. But it was still murky regarding clinical characteristics, antimicrobial susceptibility, and outcomes of CRE-BSI in these patients. We aimed to identify the potential risk factors for subsequent bacteremia and clinical outcome caused by CRE-BSI.MethodsBetween 2008 and 2020, 2,465 consecutive neutropenic children were enrolled. The incidence and characteristics of CRE-BSI were explored in CRE-colonizers versus non-colonizers. Survival analysis was performed and risk factors for CRE-BSI and 30-day mortality were evaluated.ResultsCRE-carriers were identified in 59/2465 (2.39%) neutropenic children and19/59 (32.2%) developed CRE-BSI, while 12/2406 (0.5%) of non-carriers developed CRE-BSI (P< 0.001). The 30-day survival probability was significantly lower in patients with CRE-BSI than in non-BSI (73.9% vs. 94.9%,P= 0.050). Moreover, the 30-day survival probability of patients with CRE-BSI was also poorer in CRE-carriers versus non-carriers (49.7% vs. 91.7%,P= 0.048). Tigecycline and amikacin exhibited satisfactory antimicrobial activity against all isolated strains. Fluoroquinolone sensitivity was lower inE. coli(26.3%) strains versus satisfactory susceptibility ofE. cloacaeand other CRE-strains (91.2%). CRE-BSI accompanying intestinal mucosal damage were independent risk factors for 30-day survival probability (bothP< 0.05), while combined antibiotic therapy and longer duration of neutropenia were more prone to developed CRE-BSI (P< 0.05).ConclusionCRE-colonizers were prone to subsequent BSI and CRE-BSI was regarded as an independent predictor predisposing to high mortality in neutropenic children. Moreover, individualized antimicrobial therapy should be adopted due to different features of patients with separate CRE strains.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13756-023-01269-1.