Establishment of epidemiological cutoff values against Fonsecaea monophora , an agent of chromoblastomycosis and cerebral phaeohyphomycosis
Year: 2026
Type: article
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.
Source: Journal of Clinical Microbiology
DOI: 10.1128/jcm.01846-25
Authors: Dallas J. Smith, Tijmen van Beurden, Yalong Li, Rodrigo Almeida-Paes, Bruna Jacomel, Vania Aparecida Vicente, Bruno P. R. Lustosa, Thiago Henrique Walter, Elias Nunes Monteiro Neto, Vinaykumar Hallur, Diptanu Paul, Nimmy Paul, Ruoyu Li, Sha Lu, Sarah E. Kidd, Alexandro Bonifaz, Arghadip Samaddar, Rogelio de J. Treviño-Rangel, Gloria M. González, Anuradha Chowdhary, José Guillermo Pereira Brunellie, Guillermo García-Effron, Shivaprakash M. Rudramurthy, Harsimran Kaur, Arunaloke Chakrabarti, Conceicão de Maria Pedrozo e Silva de Azevedo, Sirlei Garcia Marques, Daniel Wagner C. L. Santos, Regielly C. R. Cognialli, Flávio Queiroz-Telles, Bram Spruijtenburg, Eelco F. J. Meijer, Theun de Groot, Amir Seyedmousavi, Philippe J. Dufresne, Shawn R. Lockhart, Nathan P. Wiederhold, Yinggai Song, Ferry Hagen
Institutions: Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, Westerdijk Fungal Biodiversity Institute, Peking University, National Clinical Research, Peking University First Hospital, Fundação Oswaldo Cruz, Radboud University Medical Center, Universidade Federal do Paraná, All India Institute of Medical Sciences, Government Medical College, Sun Yat-sen University, Sun Yat-sen Memorial Hospital, South Australia Pathology, Adelaide University, The University of Adelaide, Hospital General de México, National Institute of Mental Health and Neurosciences, Universidad Autónoma de Nuevo León, University of Delhi, Universidad Nacional del Litoral, Centro Científico Tecnológico - Santa Fe, Post Graduate Institute of Medical Education and Research, Universidade Federal do Maranhão, Laboratório Cedro (Brazil), D’Or Institute for Research and Education, Hospital de Clínicas Universidade Federal do Paraná, Canisius-Wilhelmina Ziekenhuis, National Institutes of Health Clinical Center, Institut National de Santé Publique du Québec, The University of Texas Health Science Center at Houston, University Medical Center Utrecht
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Funders: Pfizer, Gilead Sciences, ARUP Laboratories, Indian Council of Medical Research, Conselho Nacional de Desenvolvimento Científico e Tecnológico, All-India Institute of Medical Sciences, National Institutes of Health, Centers for Disease Control and Prevention, Division of Graduate Education, NIH Clinical Center, NHLBI Division of Intramural Research
OpenAlex ID: W7165865102