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<p>The rise in antifungal resistance has limited treatment options for serious fungal infections, emphasizing the need for effective combination therapies. However, low-cost and rapid systems to evaluate synergy and antagonism in antifungal combinations are lacking. Here, we introduce a novel in vitro testing method for assessing antifungal interactions in C. <i>albicans</i>, enabling the simultaneous testing of three antifungal agents in a single agar plate with overnight results. This method, validated against the checkerboard assay, provides consistent fractional inhibitory concentration (FICi) measurements with reduced variability and workload. We applied this method in a comprehensive screen of 92 clinical C. <i>albicans</i> isolates for three antifungals—amphotericin B, fluconazole, and anidulafungin—yielding assessments of a total of 276 distinct combinations of antifungals and isolates. Results revealed isolate-specific interaction patterns, with amphotericin B and fluconazole showing synergy in 1% of isolates, anidulafungin and fluconazole in 19.5%, and amphotericin B and anidulafungin in 23.9%. These findings underscore the need for isolate-specific testing in clinical settings. This proposed assay aims to present a solution to that as a scalable high throughput approach to this clinical problem.</p>

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Fast detection of synergy and antagonism in antifungal combinations used against Candida albicans clinical isolates

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月15日

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  • Hanna Lundvik,
  • Ramona Santini,
  • Tugce Unalan Altintop,
  • Volkan Özenci,
  • Dan I. Andersson,
  • Nikos Fatsis-Kavalopoulos

摘要

The rise in antifungal resistance has limited treatment options for serious fungal infections, emphasizing the need for effective combination therapies. However, low-cost and rapid systems to evaluate synergy and antagonism in antifungal combinations are lacking. Here, we introduce a novel in vitro testing method for assessing antifungal interactions in C. albicans, enabling the simultaneous testing of three antifungal agents in a single agar plate with overnight results. This method, validated against the checkerboard assay, provides consistent fractional inhibitory concentration (FICi) measurements with reduced variability and workload. We applied this method in a comprehensive screen of 92 clinical C. albicans isolates for three antifungals—amphotericin B, fluconazole, and anidulafungin—yielding assessments of a total of 276 distinct combinations of antifungals and isolates. Results revealed isolate-specific interaction patterns, with amphotericin B and fluconazole showing synergy in 1% of isolates, anidulafungin and fluconazole in 19.5%, and amphotericin B and anidulafungin in 23.9%. These findings underscore the need for isolate-specific testing in clinical settings. This proposed assay aims to present a solution to that as a scalable high throughput approach to this clinical problem.