Fatal invasive pulmonary and cerebral aspergillosis due to triazole-resistant Aspergillus fumigatus with multiple CYP51A mutations.

This article discusses a case of fatal invasive pulmonary and cerebral aspergillosis caused by a triazole-resistant strain of Aspergillus fumigatus with multiple CYP51A mutations. Triazoles, such as voriconazole, are the primary treatment for invasive pulmonary aspergillosis, but triazole resistance in A. fumigatus has been increasing. The most common resistance mechanism is alterations in the CYP51A coding sequence or promoter. The patient in this case had autosomal recessive chronic granulomatous disease and had been treated with various antibiotics and voriconazole prophylaxis. Despite treatment with antifungal drugs, the patient's condition worsened and they eventually died. The isolated A. fumigatus strain had a CYP51A mutation with a 46 bp tandem repeat in the promoter and five amino acid substitutions in the coding sequence. This mutation has not been previously identified in clinical A. fumigatus isolates in Israel. It is unclear whether the mutated spores were acquired from the environment or due to prolonged voriconazole exposure. [Extracted from the article]