Authors: Justin Beardsley (University of Sydney & Westmead Institute for Medical Research, Australia)
Take a look behind the scenes of a recent Future Microbiology paper, entitled: ‘Responding to the emergence of antifungal drug resistance: perspectives from the bench and the bedside’, as we ask author Justin Beardsley about resistance mechanisms, resistance screening and new treatments in the field.
What inspired you to write this review?
As a group, we have been researching clinical and laboratory aspects of fungal infection for many years. The emergence of antifungal resistance has been largely ignored until recently. However, with resistance escalating, now seemed timely for a focused review of the current situation.
What are the main challenges for clinicians when treating serious fungal infections?
Fungal infections often require prolonged therapy with toxic drugs, and they frequently occur in frail patients. Resistance complicates therapy, and can worsen outcomes, making antifungal drug selection more complex than previously, adding to the challenges facing clinicians.
What antifungal treatments are the most promising?
Broad spectrum antifungals with good bioavailability and low toxicity are urgently required. Four of the drugs currently under development – F901318, T-2307, E121010/APX001 and ASP2397 – hold great promise. T-2307 in particular has shown broad activity against important human pathogens.
What are the key antifungal resistance mechanisms?
Increased efflux pump activity is an important resistance mechanism for all fungal pathogens, and can result in a broad spectrum of resistance. Azole resistance also occurs as a result of mutations to the enzyme responsible for ergosterol synthesis – such a mechanism has been found globally in Aspergillus fumigatus (TR34/L98H mutation in the CYP51A gene), and is thought to have resulted from exposure to agricultural azoles. Mutations to the FKS1 and FKS2 genes in Candida are responsible for echinocandin resistance, which has major repercussions for clinical management.
How can resistance be identified in the diagnostic lab?
Broth micro-dilution testing is the ‘gold standard’ for antifungal susceptibility. While this is a useful way to guide classification of an isolate as susceptible or resistant, it cannot determine if an isolate harbors a specific resistance mechanism. Molecular assays such as direct sequence analysis of specific gene targets or next generation sequencing have the ability to determine the underlying genetic basis of antifungal resistance.
What work are you hoping to do/ what do you think needs to be done in this area?
A OneHealth approach to further investigating antifungal resistance is vital. We need to understand better how to balance the need for food security with the risks to human health of using antifungals in agriculture and animal husbandry.Read the full review
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