Azole‐resistant Aspergillus fumigatus as an emerging worldwide pathogen

Abstract

Aspergillus fumigatus, a ubiquitous pathogen, causes aspergillosis in humans, especially in immunodeficient patients. Azoles are frontline antifungal drugs for treating aspergillosis. The recent global emergence of azole resistance in A. fumigatus has become a serious problem worldwide. It has arisen through two routes: long-term azole medical therapy, called the patient route, and the use of azole fungicides in its habitats especially for agricultural activities, called the environmental route. Resistant strains developed through the latter route show cross-resistance to medical azoles because of the identical molecular target Cyp51A between azole compounds used for medical treatment and agricultural disease control. In azole-resistant strains arising through the environmental route, A. fumigatus is observed frequently to possess mutations in the cyp51A gene linked to tandem repeats in the promoter region such as TR 34 /L98H and TR 46 /Y121F/T289A. The results of microsatellite genotyping analyses of resistant A. fumigatus strains have suggested a transboundary spread of this microorganism in many countries. Diverse actors are involved in the global highway of transmission. Therefore, the matter must be addressed as a "One Health" issue. This review presents a background of azole resistance in A. fumigatus and introduces newly discovered difficulties generated as this pathogen spreads worldwide.

Invasive fungal infections and oomycoses in cats 2. Antifungal therapy

“…Widespread use of azole antifungals in agriculture has been increasingly associated with azole resistance in human clinical isolates of Aspergillus fumigatus. 14 antifungal susceptibility testing would be prudent. 15,16 < Adverse effects AEs and drug-drug interactions are mostly associated with crossinhibition of mammalian cytochrome P450 enzymes, resulting in inhibition of synthesis of cholesterol, cortisol and sex steroids, as well as inhibition of cytochrome P450-dependent drugs such as ciclosporin.…”

“…Widespread use of azole antifungals in agriculture has been increasingly associated with azole resistance in human clinical isolates of Aspergillus fumigatus. 14 Although resistance is uncommon so far in veterinary clinical isolates, ongoing surveillance via antifungal susceptibility testing would be prudent. 15 , 16 …”

Design, Synthesis and Characterization of Palladium‐Functionalized Covalent Organic Framework and Its Application as Heterogeneous Catalysis for C−H Arylation of Azoles

“…Azoles are nitrogen-containing heteroaromatic compounds with important synthetic value and exhibits in a myriad of biotic activities [1] These heterocyclic compounds have shown different pharmaceutical and biological properties such as antibacterial, antiulcer, antihypertensive, antibacterial, antiviral, antifungal, anticancer, and antihistamine activities. [2][3][4] In particular, 2-substituted azoles are of particular interest and they are also frequently used in industrial dyes and quantitative detection of functional materials and DNA. [5][6][7][8] Owing to their broad application, C2 arylation of azoles is gaining importance in the synthetic field.…”

Fluconazole‐resistant Candida parapsilosis complex candidemia and analysis of mutations in the ERG11 gene from Pakistan

“…This priority list based on pathogen‐associated morbidity and mortality is also linked with the challenges of emerging drug resistance, another global health priority 3 . Apart from the ongoing threat of Candida auris , emerging resistance to azoles in Candida species and Aspergillus fumigatus are also major areas of concern 4,5 . Literature from Pakistan has highlighted the presence of drug‐resistant fungal pathogens isolated from clinical specimens 6,7 .…”

“…3 Apart from the ongoing threat of Candida auris, emerging resistance to azoles in Candida species and Aspergillus fumigatus are also major areas of concern. 4,5 Literature from Pakistan has highlighted the presence of drug-resistant fungal pathogens isolated from clinical specimens. 6,7 Pakistan is one of the first countries to report the emergence of multidrug-resistant Candida auris.…”