Establishment of epidemiological cutoff values against <i>Fonsecaea monophora</i> , an agent of chromoblastomycosis and cerebral phaeohyphomycosis

ABSTRACT Fonsecaea monophora is a dematiaceous fungus with worldwide distribution that can cause chromoblastomycosis, an implantation mycosis and a neglected tropical disease. F. monophora also causes phaeohyphomycosis, including central nervous system infections like brain abscesses, with high mortality rates. In the absence of clinical breakpoints, epidemiological cutoff values (ECVs) can aid clinicians in monitoring antifungal resistance trends and guide initial antifungal selection. To establish F. monophora MIC distribution and ECVs, we performed antifungal susceptibility testing (AFST) on F. monophora isolates. AFST data on F. monophora isolates were collected at 14 laboratories during September 2023–May 2026. Species identification was previously confirmed by DNA sequence analysis. AFST was performed by CLSI M38 standard broth microdilution method for itraconazole, voriconazole, posaconazole, isavuconazole, ketoconazole, terbinafine, flucytosine, and amphotericin B. The ECVs were established using the iterative statistical method with ECOFFinder (v2.1) following CLSI M57 guidelines. We analyzed MIC results from 137 F. monophora isolates. The calculated ECVs were itraconazole, 2 μg/mL; voriconazole, 0.25 μg/mL; posaconazole, 1 μg/mL; isavuconazole, 0.25 μg/mL; and terbinafine, 0.5 μg/mL. Amphotericin B and flucytosine had bimodal distributions, and no ECVs were set. Ketoconazole did not have data from ≥100 isolates. These F. monophora ECVs can detect non-wild-type isolates to reevaluate antifungal treatment and investigate treatment failure associated with potential clinical resistance. Established through a global multicenter collaboration, these values provide a baseline to better understand the in vitro antifungal susceptibility profile of this species and monitor resistance. IMPORTANCE Fonsecaea monophora is a dematiaceous fungus with worldwide distribution that can cause chromoblastomycosis, an implantation mycosis and neglected tropical disease of the skin and subcutaneous tissue. F. monophora also causes phaeohyphomycosis, including central nervous system infections like brain abscesses with high mortality rates. The paucity of antifungal susceptibility testing data on F. monophora complicates interpretation of minimum inhibitory concentration (MIC) values. We performed antifungal susceptibility testing on 137 F. monophora isolates to establish MIC distributions and epidemiological cutoff values (ECVs) for eight antifungals, including those commonly used to treat F. monophora infections. The calculated ECVs for commonly used antifungals were 2 μg/mL for itraconazole, 0.25 μg/mL for voriconazole, 1 μg/mL for posaconazole, and 0.5 μg/mL for terbinafine. ECVs can assist in selecting potential treatments for F. monophora and tracking antifungal resistance trends.

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Journal
Journal of Clinical Microbiology
Published
2026-06-25
DOI
https://doi.org/10.1128/jcm.01846-25
Primary Topic
Fungal Infections and Studies
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article
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article

Establishment of epidemiological cutoff values against Fonsecaea monophora , an agent of chromoblastomycosis and cerebral phaeohyphomycosis

Arghadip Samaddar, Theun de Groot, Anuradha Chowdhary, Sarah Kidd et al.
Journal of Clinical Microbiology
Fungal Infections and Studies
article

Establishment of epidemiological cutoff values against Fonsecaea monophora , an agent of chromoblastomycosis and cerebral phaeohyphomycosis

Arghadip Samaddar, Theun de Groot, Anuradha Chowdhary, Sarah Kidd, Philippe J. Dufresne, E. M. Cunha Neto, Bram Spruijtenburg, Arunaloke Chakrabarti, Yinggai Song, Dallas J. Smith, Y L Li, Shawn R. Lockhart, Nimmy Paul, Seyedmojtaba Seyedmousavi, Rogelio de J. Treviño‐Rangel, Regielly Caroline Raimundo Cognialli, Vânia Aparecida Vicente, Vinaykumar Hallur, Diptanu Paul, E Meijer, Ferry Hagen, Nathan P. Wiederhold, Sirlei Garcia Marques, Daniel Wagner C.L. Santos, R Li, Bruno P.R. Lustosa, Rodrigo Almeida-Paes, Thiago Henrique Walter, Sha Lu, Alexandro Bonifaz, Guillermo García-Effron, Gloria M. González, Bruna Jacomel, Harsimran Kaur, Shivaprakash M. Rudramurthy, Flávio Queiroz-Telles, Tijmen van Beurden, José Guillermo Pereira Brunellie, Conceicão de Maria Pedrozo e Silva de Azevedo
article en

Abstract

ABSTRACT Fonsecaea monophora is a dematiaceous fungus with worldwide distribution that can cause chromoblastomycosis, an implantation mycosis and a neglected tropical disease. F. monophora also causes phaeohyphomycosis, including central nervous system infections like brain abscesses, with high mortality rates. In the absence of clinical breakpoints, epidemiological cutoff values (ECVs) can aid clinicians in monitoring antifungal resistance trends and guide initial antifungal selection. To establish F. monophora MIC distribution and ECVs, we performed antifungal susceptibility testing (AFST) on F. monophora isolates. AFST data on F. monophora isolates were collected at 14 laboratories during September 2023–May 2026. Species identification was previously confirmed by DNA sequence analysis. AFST was performed by CLSI M38 standard broth microdilution method for itraconazole, voriconazole, posaconazole, isavuconazole, ketoconazole, terbinafine, flucytosine, and amphotericin B. The ECVs were established using the iterative statistical method with ECOFFinder (v2.1) following CLSI M57 guidelines. We analyzed MIC results from 137 F. monophora isolates. The calculated ECVs were itraconazole, 2 μg/mL; voriconazole, 0.25 μg/mL; posaconazole, 1 μg/mL; isavuconazole, 0.25 μg/mL; and terbinafine, 0.5 μg/mL. Amphotericin B and flucytosine had bimodal distributions, and no ECVs were set. Ketoconazole did not have data from ≥100 isolates. These F. monophora ECVs can detect non-wild-type isolates to reevaluate antifungal treatment and investigate treatment failure associated with potential clinical resistance. Established through a global multicenter collaboration, these values provide a baseline to better understand the in vitro antifungal susceptibility profile of this species and monitor resistance. IMPORTANCE Fonsecaea monophora is a dematiaceous fungus with worldwide distribution that can cause chromoblastomycosis, an implantation mycosis and neglected tropical disease of the skin and subcutaneous tissue. F. monophora also causes phaeohyphomycosis, including central nervous system infections like brain abscesses with high mortality rates. The paucity of antifungal susceptibility testing data on F. monophora complicates interpretation of minimum inhibitory concentration (MIC) values. We performed antifungal susceptibility testing on 137 F. monophora isolates to establish MIC distributions and epidemiological cutoff values (ECVs) for eight antifungals, including those commonly used to treat F. monophora infections. The calculated ECVs for commonly used antifungals were 2 μg/mL for itraconazole, 0.25 μg/mL for voriconazole, 1 μg/mL for posaconazole, and 0.5 μg/mL for terbinafine. ECVs can assist in selecting potential treatments for F. monophora and tracking antifungal resistance trends.

Journal of Clinical Microbiology
University of Delhi (IN), Ministry of Health and Social Welfare (TZ), Universidade Tecnológica Federal do Paraná (BR), National Skin Centre (SG), Centers for Disease Control and Prevention (US), Radboud University Nijmegen (NL), Sun Yat-sen University (CN), Universidad Autónoma de Nuevo León (MX), Peking University (CN), Hospital General de México (MX), Radboud University Medical Center (NL), University Medical Center Utrecht (NL), Universidad Nacional del Litoral (AR), Centro Científico Tecnológico - Santa Fe (AR), Institut National de Santé Publique du Québec (CA), Centro Científico Tecnológico - San Juan (AR), Sun Yat-sen Memorial Hospital (CN), D’Or Institute for Research and Education (BR), Government Medical College (IN), Laboratoire National de Référence (MA), Westerdijk Fungal Biodiversity Institute (NL), Burn Institute (US), Canisius-Wilhelmina Ziekenhuis (NL), Peking University First Hospital (CN), Hospital de Clínicas Universidade Federal do Paraná (BR), Institut National de Santé Publique (CI), Instituto Evandro Chagas (BR), National Institutes of Health Clinical Center (US), National Institute of Mental Health (US), The University of Texas Health Science Center (US), Post Graduate Institute of Medical Education and Research (IN), Universidade Federal do Maranhão (BR), Fundação Oswaldo Cruz (BR), Universidade Federal do Paraná (BR), The University of Adelaide (AU), Universidade Federal do Pará (BR), All India Institute of Medical Sciences (IN), National Institute of Mental Health and Neurosciences (IN)
Indian Council of Medical Research, National Institutes of Health
Good health and well-being
Openalex Percentile: Top 8%
Fungal Infections and Studies
DOIOpen Access PDFOpenAlex
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