Interaction diagnostics on combination treatments for Candidozyma auris : Prevalence of synergy and antagonism between antifungals in a South Korean patient cohort
Year: 2026
Type: dissertation
Abstract: Invasive fungal infections caused by multidrug-resistant pathogens represent an escalating global health burden, with Candidozyma auris emerging as a particularly dangerous nosocomial threat due to its intrinsic resistance to multiple antifungal classes and high mortality among immunocompromised patients. Although combination antifungal therapy holds theoretical promise for overcoming resistance and extending the clinical utility of existing agents, standardized methodologies for systematically evaluating drug interactions in this pathogen remain lacking. This study employed CombiANT, a gradient diffusion-based assay originally developed for antibiotic interaction testing and subsequently validated for antifungal applications, to characterize pairwise interactions among fluconazole, amphotericin B, and anidulafungin across 33 clinical C. auris isolates obtained from a South Korean patient cohort. Screening revealed a predominantly antagonistic interaction profile across all three drug combinations, with fluconazole-amphotericin B exhibiting near-universal antagonism, consistent with their mechanistically opposing modes of action on ergosterol. Notably, anidulafungin-containing combinations demonstrated comparatively elevated synergistic activity, with amphotericin B-anidulafungin and fluconazole-anidulafungin showing synergy in 16.7% and 10.5% of isolates, respectively. Directional analysis further revealed that fluconazole exerts a predominantly enhancing effect on anidulafungin activity, while the reciprocal interaction remains antagonistic. Checkerboard validation confirmed the interaction classifications generated by CombiANT, supporting the assay's reliability as a screening platform. Collectively, these findings underscore that antifungal combinations do not universally confer therapeutic benefit and highlight the importance of isolate-level evaluation, while demonstrating CombiANT's potential as a practical tool for rapid combinatorial diagnostics in clinical mycology.
Author: KARAISKOU, ELENI
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7223423112