First Report of Azole-Resistant Aspergillus fumigatus with TR46/Y121F/T289A Mutations in Kuwait and an Update on Their Occurrence in the Middle East.

Pulmonary aspergillosis is a common fungal infection with several clinical manifestations including invasive, allergic and chronic chest diseases. Invasive pulmonary aspergillosis (IPA) is a leading cause of death in immunocompromised patients, particularly those receiving chemotherapy and among bone marrow transplant recipients. Aspergillus fumigatus is the most prevalent causative agent and voriconazole is the first-line therapy for IPA. In this study, we report the first isolation of voriconazole-resistant A. fumigatus carrying TR46/Y121F/T289A mutations from an immunocompromised pregnant lady in Kuwait. The patient was successfully treated for a probable respiratory infection with caspofungin and voriconazole. The literature review from PubMed has identified itraconazole-resistant clinical and environmental A. fumigatus isolates with TR34/L98H mutations in the cyp51A from several Middle Eastern countries including Kuwait. However, clinical A. fumigatus isolates with cyp51A TR46/Y121F/T289A mutations have not been reported previously from any country in the region while environmental isolates have been reported only from Iran. The source of voriconazole-resistant A. fumigatus CYP51A TR46/Y121F/T289A mutant in our patient remained unknown. Surveillance for azole resistance among clinical and environmental isolates of A. fumigatus is warranted in Kuwait.