Empirical Therapy in High-Risk Hematological Patients with Carbapenem-Resistant Enterobacterales Colonization: Real-World Treatment Decisions and Antimicrobial Stewardship Implications

Background/Objectives: Carbapenem-resistant Enterobacterales (CRE) colonization is a risk factor for infection in hematological patients, but only a minority of colonized individuals develop invasive disease. This creates a stewardship dilemma between ensuring prompt, appropriate empirical therapy and avoiding unnecessary exposure to novel anti-CRE agents. We aimed to describe real-world empirical treatment decisions in CRE-colonized hematological patients. Methods: Retrospective single-center observational study including adult hematological patients with documented CRE colonization between January 2021–February 2025. The primary objective was to describe the use of empirical therapy active against the colonizing CRE. Secondary objectives were to evaluate concordant infections (caused by the same species and carbapenemase mechanism as the surveillance isolate) and subsequent de-escalation of CRE-active empirical therapy. Results: Thirty-two CRE-colonized patients were included. Klebsiella pneumoniae was the predominant colonizing species, and metallo-β-lactamase-producing isolates accounted for 90.6% of colonizing CRE. Empirical CRE-active therapy was administered to 20 patients (62.5%). Treated patients more frequently had febrile neutropenia and earlier colonization after hematological treatment and hospital admission. Concordant infection occurred in 5 patients (15.6%), all of whom had received empirical CRE-active therapy, whereas none of the untreated patients developed concordant infection. De-escalation was performed in 9 of 20 treated patients (45%). Conclusions: In this real-world cohort, empirical CRE-active therapy was preferentially administered to colonized patients with a high-risk clinical profile. However, concordant infection occurred in a minority of patients, highlighting the stewardship challenge of balancing early appropriate therapy with prudent use of novel anti-CRE agents.