Abstract Introduction Rhizomucor miehei is a rare cause of mucormycosis, typically affecting severely immunocompromised hosts. In the modern era of broad-spectrum prophylactic antifungal therapy, breakthrough infections with this organism remain exceptionally uncommon. The incidence of mucormycosis in patients with hematological malignancy receiving prophylactic antifungal therapy is 5.8% (Puerta-Alcalde et al., 2023). Here, we present a rare case of severe pulmonary Rhizomucor miehei in a patient on chronic immunosuppression and biopsy-confirmed remission status of Acute Myeloid Leukemia (AML). Case Description A 75-year-old female with a history of AML and prior bone marrow transplant, maintained on chemotherapy, immunosuppression, and broad-spectrum antimicrobial prophylaxis who presented with fever. Imaging of the chest on arrival to the hospital revealed a 5.2 cm right lower lobe peribronchial rounded area of reticulation with prominent ground-glass opacity, consistent with a “reverse halo sign,” a radiologic hallmark of invasive fungal infection (image 1). Initial blood cultures and sputum culture were negative, yet her respiratory status deteriorated and eventually led to requiring high-flow non-invasive oxygen supplementation. The patient was taken for a diagnostic bronchoscopy. Plasma metagenomic testing (Karius test) was sent, which detected Rhizomucor miehei in the bloodstream despite ongoing broad-spectrum empiric coverage and bronchoalveolar fluid analysis negative for fungal elements. A bone marrow biopsy demonstrated normal cellularity without blasts, confirming remission. Discussion Breakthrough mucormycosis in the setting of antifungal prophylaxis is rare but increasingly recognized, particularly among chronically neutropenic and post-transplant patients. Rhizomucor miehei is an uncommon etiologic agent, and bloodstream detection is exceedingly rare. The “reverse halo sign” seen on CT imaging is a critical diagnostic clue in immunocompromised hosts, often preceding culture confirmation. This case highlights the diagnostic utility of non-culture-based fungal detection methods, such as Karius testing, in identifying rare fungal pathogens when traditional diagnostics may be limited by prior prophylactic therapy or low organism burden. Conclusion This case underscores the importance of maintaining a high index of suspicion for breakthrough invasive fungal infections in immunocompromised patients despite prophylactic regimens. Early radiologic recognition, coupled with molecular diagnostic testing, can facilitate timely diagnosis and targeted management of rare pathogens such as Rhizomucor miehei. Reference: Puerta-Alcalde P, Monzó-Gallo P, Aguilar-Guisado M, et al. Breakthrough invasive fungal infection among patients with haematologic malignancies: A national, prospective, and multicentre study. *J Infect*. 2023 Jul;87(1):46-53. doi:10.1016/j.jinf.2023.05.005. PMID: 37201859. This abstract is funded by: None
Singh et al. (Fri,) studied this question.