Antifungal Resistance and its Evolution: An Increasing Concern

Abstract

Over the past 30 years, the importance of antifungal drugs to the practice of modern medicine has increased dramatically. Antifungal drugs used for therapy of fungal diseases can lead to antifungal resistance. Based on a study conducted by National Institute of Health, in the United States during 1980-1997, mortality rates due to invasive mycoses have been increased by 3.2 fold [1,2]. In addition, high both mortality and morbidity caused by poor diagnosis, emergence of drug-resistance and lack of effective antifungal therapy are commonly produced [2]. Nevertheless, antifungal resistance has been described for all virtually antifungal agents in several pathogens, including Candida and Aspergillus species. Additionally, azole resistance in A. fumigatus is widespread with high geographic variance since the first report of itraconazole resistance in 1997 [3]. Moreover, Candida genera exhibit resistance against almost all antifungals available, especially against Fluconazole [4-7]. For instance, C. lusitaniae and C. guillermondii are intrinsically resistant to amphotericin B [8], while other ones such as C. glabrata or C. parapsilosis are more resistant to echinocandins [3,9]. More alarming are the recent global epidemics of C. auris, which displays high resistance to all classes of antifungal drugs, eliminating effective therapeutic options [10,11]. Similarly, resistance in molds against antifungals available in the market has been demonstrated by Aspergillus fumigatus and other Aspergillus species, and even genera as Scedosporium and Fusarium [12]. For example, A. flavus and A. terreus are able to tolerate higher concentrations of amphotericin B compared to other Aspergillus species, due to different response to oxidative stress [13,14].