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.
Highlights
Fungi are among the most impactful eukaryotic microorganisms living on earth and are associated with enormous crop loss and to the extinction of various life forms [1]
We summarize the burden of antifungal resistance in the major fungal species associated with IFIs, define the cellular mechanisms underlying antifungal resistance, discuss the phenotypic methods used to distinguish susceptible and resistant fungal isolates, and explore how the application of new technologies, such as whole-genome sequencing, can impact the current paradigms of clinical practice and further of our understanding of antifungal resistance mechanisms
Different studies have investigated the epidemiological trends in Candida species infections in which only five species account for 92% of cases of candidemia–Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, and C. krusei
Summary
Fungi are among the most impactful eukaryotic microorganisms living on earth and are associated with enormous crop loss and to the extinction of various life forms [1]. Widespread use of antifungals has altered the epidemiological landscape of IFIs, where fungal species showing resistance to one and/or multiple classes of antifungals are increasingly identified in clinical settings and associated with therapeutic failure [16,17,18,19]. The epidemiology of candidemia and invasive candidiasis, as well as aspergillosis, has been the subject of numerous studies over the years looking to define the scope of fungal burden and antifungal resistance on a global scale In this context, different studies have investigated the epidemiological trends in Candida species infections in which only five species account for 92% of cases of candidemia–Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, and C. krusei. More than 15,000 invasive Candida isolates collected from 39 different countries throughout 20 years were included in a prospective antifungal susceptibility study to analyze the rate of echinocandin and azole resistance. The vast majority of data indicate a low prevalence of DHPS and DHFR mutations between 0% and 6% [60,61]
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