Necrotizing pneumonia due to blastomycosis: Diagnostic challenges and the emerging role of cell-free DNA testing

Blastomycosis is the clinical manifestation of infection caused by the yeast phase of the thermally dimorphic fungus Blastomyces dermatitidis, an environmentally poorly understood endemic North American mycosis that can progress to severe pulmonary disease in immunocompromised patients. We present a case of a 77-year-old male with a past medical history of cutaneous follicular non-Hodgkin lymphoma, renal cell carcinoma requiring total right nephrectomy, insulin dependent type 2 diabetes, and pulmonary chromoblastomycosis with left upper lobe lobectomy who presented to the emergency room for a week and a half of shortness of breath with pink tinged sputum and lethargy. He was admitted for community acquired pneumonia and initially treated with ceftriaxone and azithromycin. However, he continued to clinically deteriorate and developed acute respiratory distress syndrome (ARDS) and septic shock with secondary renal failure, requiring intubation and renal replacement therapy. Microbial cell-free DNA testing of the serum returned with 253 molecules/100 nanoliters of Blastomyces dermatitidis DNA, pulmonary blastomycosis was later confirmed by bronchoalveolar lavage cytology which directly visualized Blastomyces dermatitidis yeast. Initial treatment with Itraconazole was suspended due to suspected pulmonary toxicity and was transitioned to Isavuconazonium after completion of lipid amphotericin. He was successfully extubated after 8 days and was discharged on day 51 of admission without any supplemental oxygen requirements. This case underscores the value of rapid, noninvasive diagnostics like cfDNA testing for non-resolving pneumonia and raises the question if fungal surveillance in those who required lobectomy from prior fungal infection would mitigate future severe infections.