Potential Strategies to Control the Risk of Antifungal Resistance in Humans: A Comprehensive Review

Ali A Rabaan 1 2 3, Tarek Sulaiman 4, Shamsah H Al-Ahmed 5, Zainab A Buhaliqah 6, Ali A Buhaliqah 2, Buthina AlYuosof 7, Mubarak Alfaresi 8 9, Mona A Al Fares 10, Sara Alwarthan 11, Mohammed S Alkathlan 12, Reem S Almaghrabi 13, Abdulmonem A Abuzaid 14, Jaffar A Altowaileb 15, Maha Al Ibrahim 15, Eman M AlSalman 16, Fatimah Alsalman 17, Mohammad Alghounaim 18, Ahmed S Bueid 19, Awad Al-Omari 2 20, Ranjan K Mohapatra 21

Affiliations

18 March 2023

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doi: 10.3390/antibiotics12030608

Abstract

Fungal infections are becoming one of the main causes of morbidity and mortality in people with weakened immune systems. Mycoses are becoming more common, despite greater knowledge and better treatment methods, due to the regular emergence of resistance to the antifungal medications used in clinical settings. Antifungal therapy is the mainstay of patient management for acute and chronic mycoses. However, the limited availability of antifungal drug classes limits the range of available treatments. Additionally, several drawbacks to treating mycoses include unfavourable side effects, a limited activity spectrum, a paucity of targets, and fungal resistance, all of which continue to be significant issues in developing antifungal drugs. The emergence of antifungal drug resistance has eliminated accessible drug classes as treatment choices, which significantly compromises the clinical management of fungal illnesses. In some situations, the emergence of strains resistant to many antifungal medications is a major concern. Although new medications have been developed to address this issue, antifungal drug resistance has grown more pronounced, particularly in patients who need long-term care or are undergoing antifungal prophylaxis. Moreover, the mechanisms that cause resistance must be well understood, including modifications in drug target affinities and abundances, along with biofilms and efflux pumps that diminish intracellular drug levels, to find novel antifungal drugs and drug targets. In this review, different classes of antifungal agents, and their resistance mechanisms, have been discussed. The latter part of the review focuses on the strategies by which we can overcome this serious issue of antifungal resistance in humans.

Keywords: antifungal; antifungal resistance; fungal infections; fungal treatments.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 9 Two-dimensional structure of new antifungal agents developed.

Figure 9 Two-dimensional structure of new antifungal agents developed.

Figure 1 Flow chart depicting classification of antifungal drugs concerning the mode of action as well as names of drugs used in the management of fungal infections in humans.

Figure 1 Flow chart depicting classification of antifungal drugs concerning the mode of action as well as names of drugs used in the management of fungal infections in humans.

Figure 2 Flow chart exhibiting selection criteria adopted for selecting research publications used in the design and compilation of the present review.

Figure 2 Flow chart exhibiting selection criteria adopted for selecting research publications used in the design and compilation of the present review.

Figure 3 Two-dimensional structural formula for the most common drugs under the polyene antifungal group. All the 2D structures were plotted using the academic version of Maestro Schrödinger suite 2022 (Schrödinger Release 2022-3: Maestro, Schrödinger, LLC, New York, NY, USA, 2021).

Figure 3 Two-dimensional structural formula for the most common drugs under the polyene antifungal group. All the 2D structures were plotted using the academic version of Maestro Schrödinger suite 2022 (Schrödinger Release 2022-3: Maestro, Schrödinger, LLC, New York, NY, USA, 2021).

Figure 4 Two-dimensional structure of flucytosine used as an antimetabolite agent against invasive fungal infections.

Figure 4 Two-dimensional structure of flucytosine used as an antimetabolite agent against invasive fungal infections.

Figure 5 Two-dimensional structure of drugs under the imidazole group.

Figure 5 Two-dimensional structure of drugs under the imidazole group.

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