Novel cyp51A mutation profile in Aspergillus fumigatus from a patient with systemic lupus erythematosus and limited systemic sclerosis: first clinical case of acquired azole-resistance in Colombia

Aspergillus fumigatus is a saprophytic filamentous fungus that causes infection mostly in patients with underlying diseases, including those that alter the immune system. Despite progress in the diagnosis and treatment of this mycosis, mortality remains very high, particularly after hematogenous spread. Additionally, azole resistance can be developed in patients with long-term use of voriconazole, worsening their prognosis. However, this issue of acquired resistance has never been reported in Colombia. In fact, data on azole-resistant A. fumigatus is very limited in South America. Here we report a fatal case of a 29-year-old woman with both systemic lupus erythematosus and limited systemic sclerosis, who was initially diagnosed with chronic pulmonary aspergillosis, was treated with voriconazole for over a year, and subsequently developed invasive aspergillosis. The isolate, recovered from bronchoalveolar lavage, was identified as an azole-resistant A. fumigatus (MIC of > 32 µg/ml for voriconazole and > 1 µg/ml for itraconazole). Even though the patient started treatment with caspofungin, she was admitted to the intensive care unit and died of respiratory failure. Amplification and sequencing of the cyp51A gene, revealed the new cyp51A mutation profile TR46/F46Y/Y121F/M172V/E427K. While azole-resistant A. fumigatus occurs globally, we describe the first clinical case of acquired resistance in Colombia, where resistant isolates have been found in the soil of flower and vegetable fields, but never from a patient. This case highlights one of the major global public health concerns, which is the development of resistance in A. fumigatus, particularly in patients receiving long-term therapy with voriconazole, encouraging enhanced surveillance of resistance trends in clinical settings.