Disseminated Fungal Infection in Profoundly Immunocompromised Hosts: A Three-Case Series

Disseminated fungal infection (DFI) is uncommon in the general population but represents a severe and frequently fatal complication in immunocompromised patients, particularly those with hematologic malignancies and prolonged neutropenia. In high-risk settings, invasive fungal infections occur with clinically meaningful frequency; a large systematic review of critically ill patients reported a pooled prevalence of invasive fungal infection of approximately 5%, highlighting that while DFI is uncommon in the general population, serious fungal disease is encountered more frequently in select high-risk cohorts. We report a case series of three immunocompromised patients with DFI to highlight shared clinical patterns, diagnostic limitations, and poor outcomes. Two patients developed disseminated fusariosis with pulmonary nodules and characteristic necrotic cutaneous lesions, while the third developed <i>Scedosporium prolificans</i> fungemia with pulmonary involvement and progressive encephalopathy concerning for early central nervous system (CNS) dissemination. Diagnosis required a multimodal approach, including tissue biopsy, bronchoalveolar lavage (BAL), blood cultures, and advanced molecular testing; however, precise quantification of diagnostic delay was not systematically available across cases. In this series, diagnosis was nonetheless delayed relative to initial clinical presentation, largely due to nonspecific radiographic findings, initially negative or indeterminate cultures, overlap with bacterial or noninfectious etiologies, and the need for invasive sampling in profoundly cytopenic patients. Management was further limited by intrinsic antifungal resistance, drug toxicity, and failure of immune recovery; despite aggressive therapy, all patients experienced rapid clinical deterioration over days to weeks following diagnosis, culminating in death or transition to hospice care. These cases underscore the aggressive nature of DFI in profoundly immunocompromised hosts, the central role of neutropenia in facilitating dissemination, and the need for early recognition, multidisciplinary management, and timely goals-of-care discussions when DFI occurs in the setting of advanced immunosuppression.