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. 2024 May 29:17:2159-2168.
doi: 10.2147/IDR.S452619. eCollection 2024.

Antifungal Susceptibility and Genotypic Analysis of cyp51A Mutations in Aspergillus fumigatus Isolates in Malaysia

Xue Ting Tan  1 , Nurin Nazirah Binti Mokhtar  1 , Shirley Yi Fen Hii  1 , Fairuz Amran  1
Affiliations

Antifungal Susceptibility and Genotypic Analysis of cyp51A Mutations in Aspergillus fumigatus Isolates in Malaysia

Xue Ting Tan et al. Infect Drug Resist. .

Abstract

Purpose: Azole resistance in Aspergillus fumigatus poses a significant challenge in the management of invasive aspergillosis. This study aimed to investigate the antifungal susceptibility and cyp51A mutation profiles of A. fumigatus isolates in Malaysia.

Patients and methods: Sixty clinical A. fumigatus isolates were collected and subjected to antifungal susceptibility testing (AFST) and molecular analysis. The antifungal susceptibility testing was performed according to CLSI M38 guideline. The geometric mean (GM) minimum inhibitory concentration (MIC), MIC50/MIC90 for voriconazole, itraconazole, posaconazole, amphotericin B, and isavuconazole against A. fumigatus in non-invasive cases and invasive cases were calculated. In addition, the presence of cyp51A mutations was also identified.

Results: The present study revealed an overall resistance rate of 6.7% among the isolates. In non-invasive cases, isavuconazole and posaconazole demonstrated the lowest GM MIC of 0.08 µg/mL. Following them were itraconazole, voriconazole, and amphotericin B with concentrations of 0.15µg/mL, 0.16µg/mL and 0.90µg/mL, respectively. Similarly, in invasive cases, isavuconazole and posaconazole exhibited the lowest GM MIC of 0.09µg/mL. Following them were itraconazole, voriconazole, and amphotericin B with concentrations of 0.14µg/mL, 0.17µg/mL and 0.80µg/mL, respectively. Genotypic analysis revealed various cyp51A mutations, including F46Y, M172V, N248K, R34L, V244A, V244S, and E427K. However, not all mutations corresponded to antifungal resistance.

Conclusion: The majority of clinical Aspergillus fumigatus isolates demonstrated susceptibility to the antifungal agents tested, with isavuconazole and posaconazole demonstrating the lowest MIC values. However, cyp51A mutations were discovered without a consistent correlation to antifungal resistance, emphasising the need for additional research.

Keywords: invasive aspergillosis; isavuconazole; minimum inhibitory concentration; posaconazole; voriconazole.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Geographical locations of the hospitals in Malaysia from which A. fumigatus was isolated and provided to this study.
Figure 2
Figure 2
(a-e) Boxplot comparing MIC of voriconazole (a), itraconazole (b), posaconazole (c), amphotericin B (d) and isavuconazole (e) against invasiveness of aspergillosis. The symbols (* and °) represents extreme values of MIC. The significant differences were calculated using Mann–Whitney Wilcoxon test.
See this image and copyright information in PMC

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References

    1. Zhang S, Wang S, Wan Z, Li R, Yu J. the diagnosis of invasive and noninvasive pulmonary aspergillosis by serum and bronchoalveolar lavage fluid galactomannan assay. Biomed Res Int. 2015;2015:943691. - PMC - PubMed
    1. Thornton CR. Detection of Invasive Aspergillosis. In: Advances in Applied Microbiology. Vol 70. Academic Press Inc.; 2010:187–216. - PubMed
    1. Baddley JW. Clinical risk factors for invasive aspergillosis. Med Mycol. 2011;49:S7–S12. - PubMed
    1. Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347(6):408–415. - PubMed
    1. Lehrnbecher T, Hassler A, Groll AH, Bochennek K. Diagnostic approaches for invasive aspergillosis-specific considerations in the pediatric population. Front Microbiol. 2018;9:518. - PMC - PubMed