Mitigation of Human-Pathogenic Fungi That Exhibit Resistance to Medical Agents: Can Clinical Antifungal Stewardship Help?

Claire M Hull; Nicola J Purdy; Suzy C Moody

Disclosures

Future Microbiol. 2014;9(3):307-325. 

In This Article

Future Perspective

From a clinical perspective, the successful implementation of antifungal stewardship demands approaches that differ from those traditionally associated with antibiotic stewardship and the problem of drug-resistant bacteria – namely, efforts to reduce the indiscriminate use of antimicrobials. However, this is not to say that antifungal stewardship initiatives can have no bearing on the prevention of resistance in the clinic. In fact, evidence-based antifungal stewardship guidelines could help to minimize the selection of acquired resistance traits in fungal infections (through the appropriate choice and use of optimal antifungal dosages). Formulation of these guidelines now demands species-specific information with regard to the adaptations and basic biology of infectious agents including their intrinsic traits and any genetic factors that predispose them to resistance. Fundamental to such guidelines and also to the development of new diagnostic tools and antifungal agents is the need to collect baseline genomic information for a much wider range of fungi, including lesser-studied and emergent human-pathogenic species (Table 2 & Table 3). Here, the establishment and continued expansion of fungal genome datasets; for example, the Broad Institute Fungal Genome Initiative,[107] already serves as a point of reference for new research and understanding. From a clinical perspective, the need to rationalize the molecular taxonomy of medically important fungi has been recognized and an approval procedure for naming clinical fungi has recently been outlined.[102]

In the longer-term, the documentation of genomic and molecular information promises to underpin advances in transcriptional profiling and toxicogenomics – the study of the structure and function of a genome as it responds to xenobiotic exposure[103] and the potential to investigate toxicogenomics using yeast DNA microarrays has recently been demonstrated.[104] Ultimately, it is hoped that systems toxicogenomics will enable scientists to describe all the interactions that occur within a living system and to use our knowledge of the toxicogenomic response in one species to predict the modes-of-action of similar agents in other species.[105] Given efforts to understand and mitigate the emergence of antifungal resistance in plant-pathogenic fungi that affect cash crops,[61] such as the agricultural pest Mycosphaerella graminicola,[77] the possibility of mapping or 'following' the molecular basis of resistance in human-pathogenic fungi to combat the emergence or re-emergence of resistance traits in different species of fungi as they adapt and evolve over space and time represents a significant frontier for future research.

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