Ying Ji, Yalong Li, Weiwei Wu, Sybren de Hoog, Zhe Wan, Qian Wang, Hao Zhang, Jin Yu, Xueke Niu, Ruoyu Li, Wei Liu, Yinggai Song
{"title":"从CARD9缺陷患者中分离的黑化真菌的抗真菌敏感性：对治疗难治性感染的意义。","authors":"Ying Ji, Yalong Li, Weiwei Wu, Sybren de Hoog, Zhe Wan, Qian Wang, Hao Zhang, Jin Yu, Xueke Niu, Ruoyu Li, Wei Liu, Yinggai Song","doi":"10.1007/s11046-025-00936-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Inherited genetic deficiencies in the Caspase-associated recruitment domain-containing protein 9 (CARD9) lead to increased susceptibility of patients to opportunistic melanized fungi. Such infections are recalcitrant, and the fungus possibly acquires resistance under therapy.</p><p><strong>Objective: </strong>To evaluate differences of in vitro antifungal susceptibility of strains of melanized fungi originating from patients with CARD9 deficiency versus strains from chronic patients with unclear genetic background.</p><p><strong>Methods: </strong>We analyzed a total of 118 isolates, including 33 from patients with CARD9 deficiency, 80 from chronic patients with other undefined immunological features, and 5 environmental strains, all collected between 1997 and 2021. All isolates were identified by sequencing the ITS spacer of the rDNA operon. Broth microdilution susceptibility tests were performed according to CLSI guidelines (M38-A3document).</p><p><strong>Results: </strong>MIC ranges of strains from infected patients having CARD9 deficiency and other individuals were mostly similar. However, comparing these two groups, the GM MICs of posaconazole, amphotericin B and fluconazole in the CARD9 group were statistically higher and the GM MICs of terbinafine lower than those of undefined genetic background group. The FICI of the CARD9 group were higher than those of the undefined group in the combination of caspofungin plus amphotericin B and amphotericin B plus fluconazole, but lower than the undefined group in the combination of itraconazole plus terbinafine.</p><p><strong>Conclusions: </strong>The GM MICs for posaconazole, amphotericin B, and fluconazole were significantly elevated in the CARD9 group compared to the group with undefined chronic infections. For patients with refractory infections, conducting susceptibility testing before treatment can optimize the selection of the most effective therapeutic agent, and the combination therapy of caspofungin with amphotericin B or itraconazole may be considered the preferred treatment option.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":"190 2","pages":"29"},"PeriodicalIF":3.6000,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Antifungal Susceptibility of Melanized Fungi Isolated from CARD9 Deficient Patients: Implications for Treatment of Refractory Infections.\",\"authors\":\"Ying Ji, Yalong Li, Weiwei Wu, Sybren de Hoog, Zhe Wan, Qian Wang, Hao Zhang, Jin Yu, Xueke Niu, Ruoyu Li, Wei Liu, Yinggai Song\",\"doi\":\"10.1007/s11046-025-00936-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Inherited genetic deficiencies in the Caspase-associated recruitment domain-containing protein 9 (CARD9) lead to increased susceptibility of patients to opportunistic melanized fungi. Such infections are recalcitrant, and the fungus possibly acquires resistance under therapy.</p><p><strong>Objective: </strong>To evaluate differences of in vitro antifungal susceptibility of strains of melanized fungi originating from patients with CARD9 deficiency versus strains from chronic patients with unclear genetic background.</p><p><strong>Methods: </strong>We analyzed a total of 118 isolates, including 33 from patients with CARD9 deficiency, 80 from chronic patients with other undefined immunological features, and 5 environmental strains, all collected between 1997 and 2021. All isolates were identified by sequencing the ITS spacer of the rDNA operon. Broth microdilution susceptibility tests were performed according to CLSI guidelines (M38-A3document).</p><p><strong>Results: </strong>MIC ranges of strains from infected patients having CARD9 deficiency and other individuals were mostly similar. However, comparing these two groups, the GM MICs of posaconazole, amphotericin B and fluconazole in the CARD9 group were statistically higher and the GM MICs of terbinafine lower than those of undefined genetic background group. The FICI of the CARD9 group were higher than those of the undefined group in the combination of caspofungin plus amphotericin B and amphotericin B plus fluconazole, but lower than the undefined group in the combination of itraconazole plus terbinafine.</p><p><strong>Conclusions: </strong>The GM MICs for posaconazole, amphotericin B, and fluconazole were significantly elevated in the CARD9 group compared to the group with undefined chronic infections. For patients with refractory infections, conducting susceptibility testing before treatment can optimize the selection of the most effective therapeutic agent, and the combination therapy of caspofungin with amphotericin B or itraconazole may be considered the preferred treatment option.</p>\",\"PeriodicalId\":19017,\"journal\":{\"name\":\"Mycopathologia\",\"volume\":\"190 2\",\"pages\":\"29\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-02-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mycopathologia\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s11046-025-00936-8\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MYCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mycopathologia","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s11046-025-00936-8","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MYCOLOGY","Score":null,"Total":0}
Antifungal Susceptibility of Melanized Fungi Isolated from CARD9 Deficient Patients: Implications for Treatment of Refractory Infections.
Background: Inherited genetic deficiencies in the Caspase-associated recruitment domain-containing protein 9 (CARD9) lead to increased susceptibility of patients to opportunistic melanized fungi. Such infections are recalcitrant, and the fungus possibly acquires resistance under therapy.
Objective: To evaluate differences of in vitro antifungal susceptibility of strains of melanized fungi originating from patients with CARD9 deficiency versus strains from chronic patients with unclear genetic background.
Methods: We analyzed a total of 118 isolates, including 33 from patients with CARD9 deficiency, 80 from chronic patients with other undefined immunological features, and 5 environmental strains, all collected between 1997 and 2021. All isolates were identified by sequencing the ITS spacer of the rDNA operon. Broth microdilution susceptibility tests were performed according to CLSI guidelines (M38-A3document).
Results: MIC ranges of strains from infected patients having CARD9 deficiency and other individuals were mostly similar. However, comparing these two groups, the GM MICs of posaconazole, amphotericin B and fluconazole in the CARD9 group were statistically higher and the GM MICs of terbinafine lower than those of undefined genetic background group. The FICI of the CARD9 group were higher than those of the undefined group in the combination of caspofungin plus amphotericin B and amphotericin B plus fluconazole, but lower than the undefined group in the combination of itraconazole plus terbinafine.
Conclusions: The GM MICs for posaconazole, amphotericin B, and fluconazole were significantly elevated in the CARD9 group compared to the group with undefined chronic infections. For patients with refractory infections, conducting susceptibility testing before treatment can optimize the selection of the most effective therapeutic agent, and the combination therapy of caspofungin with amphotericin B or itraconazole may be considered the preferred treatment option.
期刊介绍：
Mycopathologia is an official journal of the International Union of Microbiological Societies (IUMS). Mycopathologia was founded in 1938 with the mission to ‘diffuse the understanding of fungal diseases in man and animals among mycologists’. Many of the milestones discoveries in the field of medical mycology have been communicated through the pages of this journal. Mycopathologia covers a diverse, interdisciplinary range of topics that is unique in breadth and depth. The journal publishes peer-reviewed, original articles highlighting important developments concerning medically important fungi and fungal diseases. The journal highlights important developments in fungal systematics and taxonomy, laboratory diagnosis of fungal infections, antifungal drugs, clinical presentation and treatment, and epidemiology of fungal diseases globally. Timely opinion articles, mini-reviews, and other communications are usually invited at the discretion of the editorial board. Unique case reports highlighting unprecedented progress in the diagnosis and treatment of fungal infections, are published in every issue of the journal. MycopathologiaIMAGE is another regular feature for a brief clinical report of potential interest to a mixed audience of physicians and laboratory scientists. MycopathologiaGENOME is designed for the rapid publication of new genomes of human and animal pathogenic fungi using a checklist-based, standardized format.
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