: Stenotrophomonas maltophilia is an emerging, multidrug-resistant pathogen increasingly associated with nosocomial infections, particularly in immunocompromised patients such as those undergoing allogeneic hematopoietic stem cell transplantation or affected by oncological diseases. Therapeutic options are limited due to intrinsic and acquired resistance mechanisms, including β-lactamases and efflux pumps. Although minocycline and trimethoprim-ulfamethoxazole are standard treatments, recent evidence suggests that eravacycline, a novel fluorocycline, may be effective in vitro, though clinical data remain scarce. Two cases of S. maltophilia bloodstream infection (BSI) in immunocompromised patients were reviewed. Both patients received eravacycline as part of combination therapy, following microbiological identification of the pathogen. Clinical course, microbiological outcomes, and antibiotic regimens were analyzed. Both patients, affected by acute myeloid leukemia and cholangiocarcinoma, developed S. maltophilia BSI after prolonged exposure to broad-spectrum antibiotics. Eravacycline (1 mg/kg every 12 hours) was included in both regimens. Blood cultures cleared within 48 hours in both cases. One patient died due to fungal complications, but S. maltophilia BSI was microbiologically controlled in both. These findings suggest a potential role for eravacycline in treating S. maltophilia BSI when standard options are limited. Further clinical studies are needed to establish efficacy and appropriate therapeutic use.
