Smith Dallas J, Melhem Marcia S C, Dirven Jessy, de Azevedo Conceição Maria Pedrozo E Silva, Marques Sirlei Garcia, Jacomel Favoreto de Souza Lima Bruna, Vicente Vania Aparecida, Teixeira Sousa Maria da Glória, Venturini James, Wiederhold Nathan P, Seyedmousavi Amir, Dufresne Philippe J, de Hoog Sybren, Lockhart Shawn R, Hagen Ferry, Santos Daniel Wagner de C L
Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
School of Medicine, Federal University of Mato Grosso do Sul, Campo Grande, State of Mato Grosso do Sul, Brazil.
J Clin Microbiol. 2025 May 14;63(5):e0190324. doi: 10.1128/jcm.01903-24. Epub 2025 Apr 4.
Chromoblastomycosis, a fungal neglected tropical disease, is acquired through traumatic inoculation and is clinically characterized by a chronic granulomatous infection of the skin and subcutaneous tissue. is the most commonly reported etiologic agent globally. Itraconazole is considered first-line therapy, but successful treatment with terbinafine, voriconazole, and posaconazole has been reported. minimum inhibitory concentration (MIC) data are limited, and epidemiological cutoffs (ECVs) are lacking; such data are important to help monitor antifungal resistance trends and guide initial antifungal selection. Thus, we performed antifungal susceptibility testing (AFST) on isolates and determined the MIC distributions and ECVs. AFST on isolates was conducted at six laboratories from October 2023 to June 2024. 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 (version 2.1) following CLSI M57 guidelines. We analyzed MIC results from 148 isolates. The calculated ECVs were itraconazole, 0.5 µg/mL; voriconazole, 0.5 µg/mL; posaconazole, 0.5 µg/mL; isavuconazole, 1 µg/mL; ketoconazole, bimodal, no ECV determined; terbinafine, 0.25 µg/mL; flucytosine, rejected; and amphotericin, 8 µg/mL. These ECVs, obtained through a multicenter international effort, provide a baseline to better understand the antifungal susceptibility profile of this species and monitor resistance. Clinicians and researchers can use these values to detect non-wild-type isolates with reduced susceptibility, reevaluate therapeutic options, and investigate potential clinical resistance if treatment failure occurs.IMPORTANCEChromoblastomycosis is a neglected tropical disease caused by an environmental, dematiaceous fungus. This fungal disease is acquired after a break in the skin that allows the fungus to enter, leading to a chronic infection in the skin and subcutaneous tissue. It is difficult to treat and often requires years of antifungal treatment. is the most reported causative agent globally. Limited antifungal susceptibility data exist for making interpreting minimum inhibitory concentration (MIC) results difficult. We performed antifungal susceptibility testing on 148 . isolates to establish MIC distributions and epidemiologic cutoff values (ECVs) for eight antifungals, including those commonly used to treat chromoblastomycosis. The calculated ECVs for the commonly used antifungals itraconazole and terbinafine were 0.5 and 0.25 µg/mL, respectively. ECVs can be helpful in choosing potential treatment options for and monitoring antifungal resistance epidemiology.
着色芽生菌病是一种被忽视的热带真菌病,通过创伤性接种感染,临床特征为皮肤和皮下组织的慢性肉芽肿性感染。是全球最常报告的病原体。伊曲康唑被认为是一线治疗药物,但也有使用特比萘芬、伏立康唑和泊沙康唑成功治疗的报道。最小抑菌浓度(MIC)数据有限,且缺乏流行病学临界值(ECV);此类数据对于监测抗真菌药物耐药趋势和指导初始抗真菌药物选择很重要。因此,我们对分离株进行了抗真菌药敏试验(AFST),并确定了MIC分布和ECV。2023年10月至2024年6月,在六个实验室对分离株进行了AFST。之前已通过DNA序列分析确认了菌种鉴定。AFST采用CLSI M38标准肉汤微量稀释法检测伊曲康唑、伏立康唑、泊沙康唑、艾沙康唑、酮康唑、特比萘芬、氟胞嘧啶和两性霉素B。根据CLSI M57指南,使用ECOFFinder(2.1版)的迭代统计方法确定ECV。我们分析了148株分离株的MIC结果。计算得出的ECV为:伊曲康唑0.5µg/mL;伏立康唑0.5µg/mL;泊沙康唑0.5µg/mL;艾沙康唑1µg/mL;酮康唑呈双峰分布,未确定ECV;特比萘芬0.25µg/mL;氟胞嘧啶不适用;两性霉素8µg/mL。这些通过多中心国际合作获得的ECV为更好地了解该菌种的抗真菌药敏谱和监测耐药性提供了基线。临床医生和研究人员可以使用这些值来检测敏感性降低的非野生型分离株,重新评估治疗方案,并在治疗失败时调查潜在的临床耐药性。重要性着色芽生菌病是一种由环境中的暗色真菌引起的被忽视的热带疾病。这种真菌病在皮肤破损使真菌进入后感染,导致皮肤和皮下组织的慢性感染。该病难以治疗,通常需要数年的抗真菌治疗。是全球报告最多的病原体。关于的抗真菌药敏数据有限,难以解释最小抑菌浓度(MIC)结果。我们对148株分离株进行了抗真菌药敏试验,以确定包括常用治疗着色芽生菌病药物在内的八种抗真菌药物的MIC分布和流行病学临界值(ECV)。常用抗真菌药物伊曲康唑和特比萘芬计算得出的ECV分别为0.5和0.25µg/mL。ECV有助于为选择潜在治疗方案和监测抗真菌药物耐药性流行病学提供帮助。