Abstract

The potential threats from fungal human pathogens are often ignored as fungal diseases are generally, not communicable among humans. Particularly, immunologically intact humans are seldom susceptible to invasive mycoses, although, fungal diseases can increase dramatically in human populations when there is an impairment of immunity, as evident from the high prevalence of cryptococcosis, candidiasis, and histoplasmosis in patients with AIDS. At present, the treatment of mycotic infections is becoming increasingly complicated because fungi are developing resistance to antifungal agents worldwide. Emergence of resistance towards the azoles, which are critically important for human therapy, are the most worrisome. In the last few years we have witnessed the emergence of a new fungal pathogens such as multidrug resistant Candida auris that exhibits resistance to fluconazole (FLU) and markedly variable susceptibility to other azoles, amphotericin B(AMB), and echinocandins. This yeast has globally emerged as a nosocomial pathogen that can cause invasive infections. Candida auris was first described in 2009 by Satoh et al. as a novel Candida species, in the Candida haemulonii complex (Metchnikowiaceae), from a patient in Japan after its isolation from the external ear canal. Alarmingly, in less than a decade this yeast, which is difficult to treat, has become widespread across several countries causing a broad range of healthcare associated invasive infections that display clonal inter- and intra-hospital transmission. The fact that this yeast exhibit MDR clonal strains which are nosocomially transmitted is unusual in other Candida species. Therefore, the possible threat of its rapid spread in affected countries and its emergence in unaffected countries will not only challenge clinicians for its effective therapeutic management but will also bring high economic burden to countries especially in resource limited settings where modern identification facilities and access to antifungals other than FLU are limited. Also, substantial increase in azole resistance among clinical Aspergillus isolates is recorded world-wide raising concern if this very effective azole class of antifungals for treatment of invasive aspergillosis will still be effective to use in the coming years. This emergence of resistance has led to the hypothesis that the deployment of demethylation inhibitors fungicides in agriculture select antifungal resistance not only in target crop pathogens but also in those fungal species that co-occur in their environment, and opportunistically infect humans, specifically the saprophytic genus Aspergillus. Two hypotheses have been proposed to explain recent increases in triazole resistance in clinical settings: (i) the use of triazoles for prophylaxis and treatment in patients with pulmonary cavities. A. fumigatus produce spores in the cavity (asexual sporulation), which is probably an important condition that facilitates resistance selection. (ii) The extensive use of triazole fungicides in agriculture can lead to selection of azole resistant A. fumigatus in the environment which may infect the susceptible patient population. Several reported cases of triazole-resistant aspergillosis developing in triazole-naıve human and animal patients support the latter hypothesis. The threats by MDR fungal pathogens will pose real challenge especially in the era witnessing ever increasing susceptible patient population but limited by new/novel antifungal arsenals availability.