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Theme III: Evolution and impact of antifungal drug resistance, and mitigation strategies

Emerging resistance to all licensed antifungal drugs is of considerable concern for effective patient management. Accelerated by our increased capacity and the recruitment of an individual with expertise in antifungal drug resistance, our focus will be to gain fundamental new insights in understanding the evolution, prevalence and mechanisms of antifungal resistance (including in emerging global and endemic pathogens), defining clinical breakpoints, testing new and combinatorial drug therapies (in terms of clinical efficacy, molecular basis for synergy and as an approach to combat antifungal drug resistance), and on improving antifungal stewardship to reduce the emergence of antifungal drug resistance. Clinical trials underlying the research aspects of this theme include the “Effect of Flucytosine and Fluconazole as Early Cryptococcosis Treatment (EFFECT) trial” recently funded by MRC/WT/DFID Global Health Trials [PI: Harrison], the EDCTP-funded “Improved flucytosine formulation for the treatment of meningitis in advanced HIV disease” [led by DNDi; Harrison], the “AMBIsome Therapy Induction OptimisatioN (AMBITION) trial” [ISRCTN 72509687, Co-PI: Harrison], and the “Paediatric Antifungal Stewardship: Optimising Antifungal Prescription (PASOAP) trial” [PI: Warris]. Support for these research activities is also provided through co-ordinated local initiatives in Exeter1 and through the GW4 AMR alliance2 (Warris is a member of the steering group).