Antifungal Susceptibility in Invasive Aspergillus Infections
Summary
Invasive aspergillosis is a life-threatening disease that principally affects immunocompromised patients, with Aspergillus fumigatus and Aspergillus flavus responsible for the majority of cases. Effective management relies on the prompt initiation of antifungal therapy and accurate determination of susceptibility profiles. Current treatment options include triazoles, echinocandins and amphotericin B, each targeting different components of fungal physiology. Triazoles inhibit lanosterol 14α-demethylase and thus disrupt ergosterol biosynthesis, echinocandins block β-1,3-D-glucan synthesis in the cell wall, while amphotericin B binds directly to ergosterol to destabilise membrane integrity. However, emerging resistance driven by mutations in cyp51 genes, overexpression of efflux pumps and alternative mechanisms such as chromosomal aneuploidy is compromising clinical outcomes. Geographical variations in resistance rates, notably azole non-wildtype isolates in sections Fumigati and Terrei, underscore the need for routine susceptibility testing. Advances in molecular identification have refined species delineation and clarified the epidemiology of cryptic species. Beyond diagnostics, the development of novel agents with distinct mechanisms of action offers new avenues to overcome resistance. Global surveillance and standardised testing methodologies remain essential to guide therapy, inform stewardship and improve prognosis in this increasingly complex therapeutic landscape.
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Antifungal Susceptibility in Invasive Aspergillus Infections publication trend
The graph below shows the total number of articles in antifungal susceptibility in invasive aspergillus infections across all publications each year (not limited to Nature Index journals).
Technical terms
Minimum inhibitory concentration (MIC): The lowest concentration of an antifungal agent that prevents visible growth of a fungal isolate in vitro.
Azoles: A class of antifungal drugs that inhibit the enzyme lanosterol 14α-demethylase, disrupting ergosterol production in fungal cell membranes.
Echinocandins: Antifungal agents that inhibit β-1,3-D-glucan synthase, impairing fungal cell-wall integrity and leading to cell lysis.
Aneuploidy: A genomic state in which cells possess an abnormal number of chromosomes, often conferring adaptive advantages under stress.
References
- The Molecular Identification and Antifungal Susceptibility of Clinical Isolates of Aspergillus Section Flavi from Three French Hospitals. Microorganisms (2023).
- Novel Antifungals and Aspergillus Section Terrei with Potpourri Susceptibility Profiles to Conventional Antifungals. Journal of Fungi (2023).
- Aneuploidy Formation in the Filamentous Fungus Aspergillus flavus in Response to Azole Stress. Microbiology Spectrum (2023).
- Resistance mechanism and proteins in Aspergillus species against antifungal agents. Mycology: An International Journal on Fungal Biology (2019).
- Point Mutations in the 14-α Sterol Demethylase Cyp51A or Cyp51C Could Contribute to Azole Resistance in Aspergillus flavus. Genes (2020).
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