At the 34th European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Global (formerly ECCMID) conference in Barcelona, Spain, drug resistance in fungi was discussed.
Antifungal drugs can be divided into five distinct classes: azoles, echinocandins, polyenes, pyrimidine analogue flucytosine, and allylamines. While these therapies have generally been efficacious and safe at targeting fungal infections, the rise in antifungal resistance in recent years represents a burgeoning global health concern that is jeopardizing the effectiveness of existing treatment options and leading to higher rates of morbidity and mortality globally.
A study conducted in Denmark assessing the presence of resistant Aspergillus fumigatus showed that the presence of the microorganism increased between 2020 and 2022 in both Danish soil and air. The main resistant isolate observed in the sample harbored the TR34 mutation, with the few TR46 isolates only presenting in the environment during the later years of the study. Another study in Spain surveying the presence of clinical azole-resistant A. fumigatus, also demonstrated that the majority of isolates had the TR34-L98H substitution. The survey was first conducted in 2019 where 54% of isolates had the TR34 mutation, but 79% of isolates within the sample presented with the TR34 substitution in 2022. This strain seems to be particularly prevalent in the Mediterranean region, and the study authors noted that pesticide use is likely driving this resistance in Spain.
Another pathogen of note is Candida parapsilosis. It is a common candida that is responsible for the vast majority of candidemia infections and has been responsible for various epidemics. Recently, the global emergence of fluconazole-resistant C. parapsilosis has raised concerns globally. A nationwide multicenter study on azole resistance in C. parapsilosis in France demonstrated that 10.6% of samples harbored resistant isolates, yet resistance varied from center to center. In particular, an elevated level of resistance was observed in Paris. Another such study in China showed that 2.4% of C. parapsilosus isolates were resistant to fluconazole. While the abundance of resistant isolates is low in China, various outbreaks and cases of clonal transmission can be observed, mainly caused by the Erg11Y132F mutation.
Candida tropicalis is the largest contributor to invasive candidiasis infections in the Asia-Pacific region, and the third largest contributor globally. A study in India analyzing 799 C. tropicalis isolates collected from 26 hospitals across the country over a 10-year period showed that only 6% of isolates were resistant to fluconazole. Of these, 42.5% of isolates were cross-resistant to voriconazole, and 57.5% were cross-resistant to itraconazole. All fluconazole-resistant isolates had the Y123F amino acid substitution in the ERG11 gene. Because the ERG11 gene is the azole target, mutations in this gene lead to alternate protein structure and thus reduce the fluconazole binding capacity, leading to resistance. This resistance is a great concern as fluconazole is a first-line treatment in low- and middle-income countries (LMIC).
As evidenced by these studies, antifungal resistance is on the rise and is a global issue. Antifungal resistance surveillance is therefore vital in order to continue to monitor and evaluate this threat. More research into novel therapies with alternate mechanisms of action should also be a key priority in order to combat the growing resistance to existing drugs and to alleviate the morbidity and mortality from fungal infections.
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