S4.5c Using serum beta-glucan measurements and sequencing of the Madurella mycetomatis azole target gene to predict therapeutic outcome during azole treatment in human mycetoma
Abstract
Abstract S4.5 Mycetoma Clinical Trial on fosravuconazole treatment in eumycetoma– Top Line Results, September 22, 2022, 10:30 AM - 12:00 PM Objectives Eumycetoma is a neglected tropical disease characterized by large subcutaneous swellings and the formation of grains and most commonly caused by Madurella mycetomatis. The currently recommended therapy is a combination of antifungal therapy with an azole and surgery. Itraconazole is the current recommended drug and fosravuconazole, the pro-drug of ravuconzole, is currently clinically investigated. At the moment, there are no epidemiological cut-off values (ECV) for M. mycetomatis for either of these drugs or rapid diagnostic tests which can predict the therapeutic outcome of these treatments. Therefore, in this study, we determined the ECV for these drugs and determined whether there was a correlation between minimal inhibitory concentration (MIC) and the DNA sequence of the azole target gene CYP51A. We also assessed beta-glucan concentrations in the serum of mycetoma patients during treatment to establish whether any of these values were predictive for therapeutic outcomes. Methods In order to determine the ECV for M. mycetomatis, MIC distributions for itraconazole and ravuconazole were determined in genetically diverse clinical M. mycetomatis isolates using the ECOFFinder software. CYP51A sequences were sequenced and comparisons were made between the different CYP51A variants and the MIC distributions. Beta-glucan…
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