Risk factors for bloodstream infection caused by carbapenem-resistant Enterobacterales in patients with haematological malignancies: a systematic review and meta-analysis

With the aim to identify risk factors associated with bloodstream infections (BSI) caused by carbapenem-resistant Enterobacterales (CRE) in patients with hematological malignancies (HM), a systematic review and meta-analysis were conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251176369). MEDLINE, PubMed, and Embase were searched for studies published up to 31 October 2025. Observational studies evaluating risk factors for laboratory-confirmed CRE BSI in adult or paediatric patients with HMs were included. Adjusted and unadjusted effect estimates were analysed separately. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random- or fixed-effects models based on heterogeneity. Six studies were included. In meta-analyses based on adjusted estimates, prior exposure to carbapenems (OR 8.01, 95% CI 2.98-21.54), cephalosporins (OR 4.11, 95% CI 1.53-11.05) and fluoroquinolones (OR 3.94, 95% CI 1.83-8.44) resulted to be associated with CRE BSI. Meta-analyses of crude data showed additional associations with CRE colonization, previous infections, newly diagnosed disease or first relapse, chronic liver disease, diabetes mellitus, and prior exposure to multiple antibiotic classes. Prior exposure to carbapenems, cephalosporins, and fluoroquinolones was consistently associated with CRE BSI in adjusted analyses. However, the small number of included studies and the wide confidence intervals limit the precision and generalizability of these estimates. Previous antibiotic exposure should therefore be considered as part of an integrated risk assessment together with colonization status, previous microbiological findings, clinical severity, and local epidemiology, rather than as a stand-alone criterion for empirical therapy.