Active Infection & Immunity

COMBAT Candida - COMBination Antifungal Therapy for Candida Bloodstream Infections

Funder Wellcome Charity-funded
Recipient organisation University of the Witwatersrand
Funding £5.5M
Period Mar 2025 — Feb 2030

In plain English

AI plain-English summary

A clinical trial in South Africa will test whether combining two antifungal drugs—micafungin and flucytosine—can save more lives from *Candida* bloodstream infections than standard treatment alone. *Candida* species now account for five of the eleven fungal pathogens on the WHO’s highest-priority list. Mortality from these infections hovers around 30%, and resistance to existing antifungals is rising fast, particularly in settings like South Africa. Current single-drug regimens often fail to clear the infection quickly enough or drive resistance during treatment. This trial directly tests whether a two-drug combination can improve survival, clear the fungus faster, and suppress the emergence of resistant strains—all at once. If the combination proves safe and cost-effective, it could become a readily implementable global standard for candidaemia treatment. That would shift practice in intensive care units and hospitals worldwide, where these infections are a growing threat. The trial also includes a health economics analysis, so funders and policymakers will know whether the regimen delivers value for money. A parallel programme using mouse models and genomic surveillance will clarify how resistance emerges and spreads, feeding back into future treatment guidelines.

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. "

View the original record at the funder ↗

Researchers

Nelesh Govender (EPMC Awardee)

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Original classification

Discretionary Award

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