Epidemiological cut-off values for itraconazole and ravuconazole for Madurella mycetomatis, the most common causative agent of mycetoma

by Nyuykonge B, Siddig EE, Mhmoud NA, Nyaoke BA, Zijlstra EE, Verbon A, Bakhiet S, Fahal AH, van de Sande W. Mycoses 2022. doi: 10.1111/myc.13509

Summary: A prodrug of ravuconazole, fosravuconazole, is being investigated for the treatment of eumycetoma in an ongoing clinical study, but there are no clinical breakpoints or epidemiological cut-off values (ECV) to guide treatment for either ravuconazole or the existing treatment itraconazole. The authors describe a study to determine tentative ECVs for both drugs in Madurella mycetomatis, the main causative agent of eumycetoma. Minimal inhibitory concentrations for itraconazole and ravuconazole were determined in 131 genetically diverse clinical M. mycetomatis isolates and used to determine ECVs. Sequencing of the azole target gene, CYP51A, revealed two mutants, but these were not linked to decreased susceptibility to itraconazole and ravuconazole. The proposed M. mycetomatis ECV is 1 mg/L for itraconazole and 0.064 mg/L for ravuconazole.

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