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Review
. 2020 Dec 8;9(12):877.
doi: 10.3390/antibiotics9120877.

Drug-Resistant Fungi: An Emerging Challenge Threatening Our Limited Antifungal Armamentarium

Amir Arastehfar  1 , Toni Gabaldón  2   3   4 , Rocio Garcia-Rubio  1 , Jeffrey D Jenks  5   6   7 , Martin Hoenigl  6   7   8 , Helmut J F Salzer  9 , Macit Ilkit  10 , Cornelia Lass-Flörl  11 , David S Perlin  1
Affiliations
Review

Drug-Resistant Fungi: An Emerging Challenge Threatening Our Limited Antifungal Armamentarium

Amir Arastehfar et al. Antibiotics (Basel). .

Abstract

The high clinical mortality and economic burden posed by invasive fungal infections (IFIs), along with significant agricultural crop loss caused by various fungal species, has resulted in the widespread use of antifungal agents. Selective drug pressure, fungal attributes, and host- and drug-related factors have counteracted the efficacy of the limited systemic antifungal drugs and changed the epidemiological landscape of IFIs. Species belonging to Candida, Aspergillus, Cryptococcus, and Pneumocystis are among the fungal pathogens showing notable rates of antifungal resistance. Drug-resistant fungi from the environment are increasingly identified in clinical settings. Furthermore, we have a limited understanding of drug class-specific resistance mechanisms in emerging Candida species. The establishment of antifungal stewardship programs in both clinical and agricultural fields and the inclusion of species identification, antifungal susceptibility testing, and therapeutic drug monitoring practices in the clinic can minimize the emergence of drug-resistant fungi. New antifungal drugs featuring promising therapeutic profiles have great promise to treat drug-resistant fungi in the clinical setting. Mitigating antifungal tolerance, a prelude to the emergence of resistance, also requires the development of effective and fungal-specific adjuvants to be used in combination with systemic antifungals.

Keywords: antifungal resistance; antifungal susceptibility testing; azole; echinocandin; identification; therapeutic drug monitoring; whole-genome sequencing.

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Conflict of interest statement

M.H. received research funding from Gilead and Pfizer. D.S.P. receives research support and/or serves on advisory boards for Amplyx, Cidara, Scynexis, N8 Medical, Merck, Regeneron, and Pfizer. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. The rest of the authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Worldwide prevalence of non-albicans Candida species causing candidemia.
Figure 2
Figure 2
General mechanisms of azole resistance mechanisms employed by Candida and Aspergillus species covered in this study. The drug-target modulating and overexpression of efflux pumps and drug target are the most common strategies counteracting the azole efficacy used by these species.
See this image and copyright information in PMC

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