Isolated Cryptococcus Bloodstream Infection in a Non-HIV Patient Following Rituximab Therapy for B-Cell Lymphoma: A Therapeutic Challenge and Literature Review

Background: Cryptococcus neoformans is an opportunistic fungal pathogen that primarily affects immunocompromised individuals, particularly those with advanced HIV/AIDS. However, an increasing number of cases are being identified in non-HIV immunocompromised hosts, including patients receiving B-cell-depleting therapies such as Rituximab. Case Presentation: A 67-year-old male with marginal B-cell lymphoma developed an isolated cryptococcal bloodstream infection shortly after completing Rituximab therapy. Initially, the patient presented with persistent diarrhea and progressive weakness. Subsequently, acute otitis media developed, and Streptococcus pneumoniae bacteremia was diagnosed. During his hospital course, his repeated blood cultures were cleared of bacteria but revealed Cryptococcus neoformans, confirmed by a positive serum cryptococcal antigen (titer 1:40). Given the patient’s severe coagulopathy, a lumbar puncture was not feasible, necessitating an alternative diagnostic approach. Adhering to IDSA guidelines, he received a 2-week induction phase of amphotericin B and flucytosine, followed by consolidation and maintenance therapy with fluconazole. The patient successfully completed his induction therapy as an inpatient without complications and demonstrated clinical recovery at a subsequent follow-up visit. Conclusion: This case study highlights the expanding spectrum of cryptococcosis beyond HIV/AIDS and underscores the paramount importance of early recognition and treatment, adhering to established guidelines, in the context of Rituximab-associated immunosuppression. Further research is needed to refine risk stratification of isolated cryptococcus bloodstream infection and develop tailored management strategies for this emerging at-risk population.