tNGS-guided diagnosis of pulmonary mucormycosis with bacterial coinfection in new-onset diabetes: a case report

Abstract

Pulmonary mucormycosis is a rapidly progressive and potentially fatal fungal infection, particularly in patients with uncontrolled diabetes. Early diagnosis can be challenging when invasive tissue sampling is high-risk or infeasible. Targeted next-generation sequencing (tNGS) may provide an adjunctive approach for identifying pathogens in clinically suspected invasive fungal infections. We report a case of a 50-year-old man with no known medical history who presented with fever, weight loss, and a cavitary pulmonary lesion. Laboratory evaluation revealed newly diagnosed, poorly controlled diabetes (HbA1c, 11.4%). Bronchoalveolar lavage (BAL) fluid was evaluated using conventional microbiological testing and tNGS. Lung biopsy was deferred because of the patient’s malnutrition, uncontrolled diabetes, and hypoxemia. BAL fluid tNGS detected Rhizopus microsporus (4945 reads) and Streptococcus agalactiae (3396 reads), whereas conventional bacterial and fungal cultures were negative. Gram staining showed Gram-positive cocci without fungal elements. The combination of uncontrolled diabetes, compatible CT findings, detection of Rhizopus microsporus in BAL fluid by tNGS, and the subsequent clinical course supported the diagnosis. Histopathological confirmation was not obtained. The patient was treated with isavuconazole, targeted antibacterial therapy, glycemic control, and nutritional support, without surgical intervention, and subsequently improved clinically and radiologically. This case highlights the potential utility of tNGS as an adjunctive diagnostic approach for suspected pulmonary mucormycosis when tissue biopsy is high risk or infeasible. Integration of tNGS findings with clinical and radiological evidence may facilitate timely management while avoiding unnecessary invasive diagnostic procedures.