Associated organisationsNational Health Service · St George's, University of London · University of Cape TownEurope PMC affiliations are not treated as award recipients or mapped locations.
Funding£1.6M
PeriodFeb 2025 — Feb 2030
In plain English
AI plain-English summary
Fungal bloodstream infections kill roughly 30% of patients who contract them, and the drugs used to treat them are losing effectiveness. This clinical trial will test whether giving two antifungal drugs together—micafungin and flucytosine—can save more lives and slow the rise of drug-resistant *Candida* fungi. The problem is urgent. *Candida* species now account for five of the eleven fungal pathogens the World Health Organization lists as high or critical priority. Resistance to existing single-drug treatments is increasing, particularly in high-burden settings like South Africa, where this phase IIb trial will run. The trial uses an innovative design that tracks not just survival, but also how quickly the fungus clears from the blood and whether resistance emerges during treatment. If the combination proves safe and effective, the regimen could be rolled out globally to treat candidaemia. That would give clinicians a ready-to-use weapon against a deadly infection that is becoming harder to treat with standard drugs. The research also includes laboratory studies of how resistance develops and a health economics analysis to determine whether the approach is cost-effective for health systems.
View original technical description
Candida species make up 5 of the 11 WHO-listed high and critical priority fungal pathogens due to rising incidence, high mortality (~30%) and increasing antifungal resistance. Combination antifungal therapy with micafungin and flucytosine has potential to improve clinical outcomes, while mitigating resistance emergence, yielding benefit to public health as well as the individual. This approach will be tested in a phase IIb randomised controlled trial in South Africa, a high burden setting for antifungal resistance, for safety and efficacy in the treatment of Candida bloodstream infections. An innovative trial design will select the appropriate dose of flucytosine for this indication, and incorporate resistance, as well as mortality and fungal clearance as components of a hierarchical composite primary endpoint for Win Ratio analysis. A programme of work garnering evidence around Candida epidemiology, transmission dynamics, and resistance mechanisms induced by antifungal exposure in patients, and using a murine model of South African clade Candida auris will complement trial findings. A health economics analysis will assess cost-effectiveness of the intervention. If safe and effective for improving clinical, mycological and resistance outcomes in this high burden setting, this combination regimen will be readily implementable to optimise candidaemia treatment and prevent antifungal resistance emergence globally.
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