Concurrent Mold, Mycobacterial, and Viral Infections in a Hematopoietic Stem Cell Transplant Recipient Undergoing Lung Transplantation for Graft-Versus-Host Disease

Hematopoietic stem cell transplant (HSCT) recipients are at high risk for opportunistic infections due to profound immunosuppression and graft-versus-host disease (GvHD). Molds and nontuberculous mycobacteria (NTM) pose diagnostic and therapeutic challenges, especially when infections overlap. A 42-year-old woman with prior allogeneic HSCT for acute myeloid leukemia (AML) developed pulmonary infections with <i>Microascus</i> spp. and <i>Mycobacterium chimaera</i>, later complicated by <i>Aspergillus calidoustus</i> and RSV infection. Initial therapy included voriconazole, amphotericin B, and a macrolide-based multidrug regimen for NTM. Modifications were required for drug resistance and hepatotoxicity. Despite partial response, recurrent fungal infection necessitated prolonged antifungal therapy, including adjunctive inhaled amphotericin B and terbinafine. Ultimately, progressive bronchiolitis obliterans prompted bilateral lung transplantation. Explant pathology revealed necrotizing granulomas positive for NTM and <i>Microascus</i> spp. Post-transplant prophylaxis with voriconazole, rifabutin, azithromycin, and inhaled amikacin prevented recurrence, and the patient remained clinically stable at 6-month follow-up. This case illustrates the complexity of managing overlapping mold and NTM infections in HSCT recipients, highlighting the need for individualized, multidisciplinary care. Therapeutic drug monitoring, careful adjustment for drug-drug interactions, and the use of adjunctive inhaled antifungals were critical to achieving a favorable outcome.