Cyp51A gene mutations and azole resistance in clinical and environmental isolates of Aspergillus flavus from Pakistan

Author:

Professor Kauser Jabeen (PK)

Abstract:

Background:
A. flavus is the second most common cause of Invasive Aspergillosis worldwide, with higher prevalence reported in regions like Asia, Middle East and Africa. It is the most common Aspergillus spp. from both clinical and soil samples in Pakistan. There is a global concern for management of aspergillosis with the emergence of azole resistant Aspergillus species. A study from Asia reported over 85% resistance to at least one azole in Aspergillus flavus. Considering this high azole resistance in the region, it is important to determine the susceptibility of A. flavus against azoles in Pakistan.
Objectives:
In this study, we determined minimum inhibitory concentrations (MICs) of itraconazole, voriconazole, and posaconazole in A. flavus isolated from clinical and environmental specimens using broth microdilution (BMD). We also sequenced cyp51A gene for detection of mutations associated with triazole resistance.
Methods:
MICs of 203 (146 clinical and 74 environmental) A. flavus strains from different regions of Pakistan were determined by BMD using the Clinical and Laboratory Standards Institute (CLSI) M38 guidelines. The results were interpreted according to the epidemiological cut-off values (ECVs) established in 2022 by CLSI. Cyp51A gene mutation was explored in 34 isolates. Fungal DNA was extracted using commercially available DNA isolation kit. The cyp51A gene was amplified and sequenced in both directions.
Results:
The clinical Aspergillus flavus isolates had MIC50 and MIC90 of 0.25/0.5 ug/ml for itraconazole, 0.5/1 ug/ml for voriconazole, and 0.25/0.5 ug/ml for posaconazole. The environmental isolates had MIC50 and MIC90 of 0.125/0.25 ug/ml for itraconazole, 0.5/0.5 ug/ml for voriconazole, and 0.125/0.25 ug/ml for posaconazole. Two clinical and nine environmental isolates had MIC above ECV for posaconazole and six environmental isolates had MIC above ECV for itraconazole. No mutation was detected in 34 A. flavus isolates screened for cyp51A gene mutation.
Conclusions:
Identification of Aspergillus flavus strains with MICs above ECVs for posaconazole and itraconazole is concerning. Ongoing antifungal resistance surveillance studies are needed to monitor the emergence of azole resistance in A. flavus.

Abstract Number: 4

Conference Year: 2024

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