Background: Patients with hematological malignancies (HM) or undergoing hematopoietic cell transplantation (HCT) face high risk of bloodstream infections (BSI) during febrile neutropenia. Rising antimicrobial resistance (AMR), especially among Gram-negative (GN) bacteria, challenges effective empirical antibiotic therapy (EAT) selection. This ECIL-10 systematic review updates European resistance epidemiology since the 2011 ECIL-4 guidelines publication to inform clinical recommendations.
Methods: We conducted a systematic review (ID: CRD42025638003) of bacterial epidemiology and resistance in HM/HCT patients across Europe, from June 2011 to September 2024, using PubMed, Embase, and Web of Science according to PRISMA guidelines. We included studies reporting BSI or colonization rates and resistance patterns, including extended-spectrum beta-lactamase-producing/third-generation cephalosporin-resistant (ESBL/3GCR), fluoroquinolone-resistant (FQ-R) carbapenem-resistant (CR), and multidrug-resistant (MDR) for GN bacteria; methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) for Gram-positive (GP) bacteria. Two reviewers independently extracted data with ECDC/EARS-Net surveillance 2011 and 2022 data providing supporting analysis. We examined fluoroquinolone prophylaxis (FQ-P) impact on BSI rate and resistance.
Results: Analysis included 40 studies (33,387 patients/febrile episodes from observational studies and 21,402 patients from one meta-analysis) across 12 European countries. BSI prevalence averaged 30% (range, 15-59%), with 42% GN and 51% GP distribution. Median resistance rates among GN BSI were: 55% for FQ-R, 30% for ESBL/3GCR, 13% for both CR and MDR. CR reached 26% in P. aeruginosa (PsA) and 38% in K. pneumoniae (KPn). Among GP BSI resistance was 3% for MRSA and 1% for VRE. Colonization studies demonstrated 20% ESBL/3GCR and 5% CR rates. We identified a southeastern European resistance gradient and significant temporal increase in ESBL/3GCR, CR KPn, and MDR PsA, confirmed in ECDC/EAR-Net analysis. FQ-P reduced overall and GN BSI incidence but increased FQ-R and ESBL/3GCR GN infections in adults. In children, FQ-P reduced BSI in leukemia but not in HCT and data on resistance were inconclusive. ECIL-10 proposed resistance reporting aligned with ESCMID/IDSA guidelines.
Conclusions: AMR presents an escalating challenge in febrile neutropenic HM/HCT patients with geographical variability and increasing resistance trends. These findings strongly support the need for updated guidelines, antimicrobial stewardship programs, rapid diagnostics implementation, and prospective studies to optimize effective empirical therapy strategies.
