A bloodstream infection with the fungus *Candida* kills roughly half of the patients who contract it, and standard drugs are increasingly failing. Researchers leading this international network will pool samples and data from around 700 patients across four clinical trials in Europe and South Africa to identify better ways to predict which treatments will work. Current trials need hundreds of patients per group to show one drug is better than another, and they ignore the risk of the fungus developing resistance. This project aims to find biomarkers—measurable signs such as how fast the fungus is cleared from the blood, its genetic tendency to resist drugs, or the patient’s own immune response—that could serve as earlier, more accurate indicators of treatment success. If successful, these biomarkers would allow future clinical trials to test new antifungal drugs faster and with far fewer patients, weeding out ineffective treatments before they reach large-scale testing. The work is applied clinical research: it directly targets a practical bottleneck in drug development for a lethal hospital infection, with the goal of saving lives by getting better treatments to patients sooner.
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Candida is a fungus that usually lives harmlessly in the human gut but can cause severe bloodstream infection (candidaemia) in patients in hospital, resulting in death in ?50% of cases. Increasing resistance to first-line antifungals contributes to this, and new approaches are needed. Current clinical trials to test these agents require hundreds of patients per arm to confidently demonstrate that one treatment is better than another in reducing death or clearing infection in candidaemia- with no account taken of the likelihood that Candida will become resistant to it. To make the process quicker at weeding out poorly performing drugs at an earlier stage, we need more accurate predictors of which patients will respond to treatment, and measures of that response, so-called biomarkers. These could relate to how quickly the Candida fungus is cleared from the body, its propensity to persist and develop resistance, and/or the human immune response against Candida. In this project, led by experienced fungal clinical and laboratory researchers, we will create an international network to share knowledge and standardise collection of samples, pool and integrate data from 4 European and South African clinical trials in candidaemia (total ?700 patients). We will use novel, cutting-edge laboratory (including genomics and gut fungal microbiome studies) and statistical methods (including machine learning) to analyse our collective samples in order to establish the most accurate biomarkers for use in future trials to determine the best treatment for (antifungal-resistant) Candida.
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