Screening For Azole Resistance Genes In Aspergillus Keratitis: Epidemiology, Genetic Expressions And Treatment Outcome

To study the most common azole resistance gene regulation of mostly identified filamentous fungi (Aspergillus fumigatus) associated with keratitis.

Tertiary eye care center of eastern India

100 cases of culture positive Aspergillus keratitis patients were enrolled for this study between Jan 2022 to December 2023. There were two groups formed: one of patients who had previously been exposed to azole for at least 3 weeks, and the other of patients who had never been exposed to azole. All patients had a detailed clinical evaluation followed by corneal scraping. After growing Aspergillus in culture, scraping material was sent for an azole resistance gene expression study for specific genes like (Cyp51, L98H, T289A, Y121F).

Out of 100 cases, 60 cases (60%) were previously exposed to the azole group of antifungals, and 40 cases (40%) had no prior exposure. In group A, multiple resistance gene expressions were noted as they are azole-exposed. Among the 60 cases, 48 (80%) showed upregulation of expression of more than two resistant genes (Ct value range 15–28 in qPCR). No upregulation of gene expressions was found in group B, where the rest of the 40 cases were not exposed to azoles. The best medical management outcome was found in group B, and in group A, around 85% of cases needed surgical intervention due to the severity of the infection. 

Screening for azole resistance is an important approach to initiating antifungal medications. This work highlights the magnitude of azole-resistant Aspergillus associated keratitis and addresses the therapeutic options available. No community azole resistance was found in non-azole exposure group patients.