Maria Dolores Sánchez, Nathalie Clément, Agathe Cailleau, Céline David, Nadine Brisseau, Anne Lehébel, Faraj Fajloun, Jacques Guillot, Antoine Rostang
{"title":"Comparison of three culture media for testing susceptibility of Malassezia pachydermatis to four antifungal agents by a microdilution method and gradient diffusion strips.","authors":"Maria Dolores Sánchez, Nathalie Clément, Agathe Cailleau, Céline David, Nadine Brisseau, Anne Lehébel, Faraj Fajloun, Jacques Guillot, Antoine Rostang","doi":"10.1093/mmy/myag036","DOIUrl":"10.1093/mmy/myag036","url":null,"abstract":"<p><p>The yeast Malassezia pachydermatis frequently causes otitis externa and dermatitis in dogs and cats. This often requires prolonged antifungal therapy, raising concerns about reduced susceptibility. Antifungal susceptibility testing (AFST) for Malassezia spp. remains challenging because many protocols require complex lipid supplementation and are difficult to implement in routine veterinary settings. Here, we compared three culture media for AFST of M. pachydermatis: (i) a complex, lipid-enriched RPMI formulation (RPMI1); (ii) a simplified RPMI formulation supplemented with Tween 40 and Tween 80 (RPMI2); and (iii) a Sabouraud dextrose medium supplemented with Tween 80 (SD). Forty-nine canine clinical isolates were tested against ketoconazole, itraconazole, posaconazole and terbinafine using a colorimetric broth microdilution approach and a gradient diffusion method on solid media (EzyMIC®). RPMI1 broth was unstable after freezing, resulting in weak or ambiguous resazurin readings and frequent data exclusions, and the solid formulation of RPMI1 was unsuitable for reliable gradient diffusion interpretation. By contrast, RPMI2 medium provided consistent minimal inhibitory concentration (MIC) determinations for azoles in both solid and liquid media, with comparable MIC values. Conversely, terbinafine MICs were frequently elevated in RPMI-based liquid media, often exceeding the upper testing range, whereas lower and more readily interpretable MIC values were obtained on SD agar, suggesting medium-dependent effects on terbinafine assessment. The results obtained with SD media on azoles were more heterogeneous. Overall, RPMI2 offered a practical and reproducible option for azole susceptibility testing of M. pachydermatis, while terbinafine results may require cautious interpretation depending on the testing medium.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genomic characterization of sexually transmitted Trichophyton mentagrophytes genotype VII causing genital dermatophytosis in Italy.","authors":"Valeria Gaspari, Giulia Lombardi, Claudio Foschi, Donatella Lombardo, Raul Cetatean, Andrea Liberatore, Eva Caterina Borgatti, Jessica Landi, Benedetta Secci, Gionathan Orioni, Tiziana Lazzarotto, Simone Ambretti","doi":"10.1093/mmy/myag046","DOIUrl":"10.1093/mmy/myag046","url":null,"abstract":"<p><p>Dermatophytes are among the most common causes of superficial fungal infections worldwide. In recent years, an increasing number of cases of sexually transmitted dermatophytosis have been reported in Europe, mainly associated with Trichophyton mentagrophytes genotype VII. Genomic data on circulating strains remain limited, particularly in Southern Europe. In this study, we described three cases of sexually transmitted dermatophytosis caused by T. mentagrophytes genotype VII diagnosed in Italy and characterized using whole genome sequencing. Skin scale samples were collected from genital/perigenital lesions and processed for mycological culture, antifungal susceptibility testing, and genomic analysis. Internal transcribed spacer (ITS) region sequencing confirmed the identification of genotype VII in all isolates. Phylogenetic analysis based on ITS sequences and phylogenomic analysis based on core genome single nucleotide polymorphisms consistently showed that the three isolates clustered within the genotype VII lineage and were closely related to previously described European strains. Antifungal susceptibility testing revealed low Minimum Inhibitory Concentration (MIC) values for extended-spectrum triazoles (voriconazole and posaconazole) and amphotericin B. Genomic analysis demonstrated that all isolates carried the wild-type SQLE gene, with no mutations associated with terbinafine resistance. Sequence variations were observed in several members of the MEP protease gene family and in the ZafA transcription factor gene. These findings confirm the presence of sexually transmitted T. mentagrophytes genotype VII in Italy and support the hypothesis that this genotype is an emerging cause of dermatophytosis in Europe. The integration of genomic approaches with clinical and epidemiological data may improve the understanding of transmission dynamics and help identify potential outbreaks.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Candida (Candidozyma) auris strains exposed to azole fungicides become less susceptible to manogepix.","authors":"Audrey Boutillier, Adrien Baillod, Jérémy Moreau, Jérôme Labanowski, Sandrine Marchand, Jonathan Clarhaut, Kévin Brunet","doi":"10.1093/mmy/myag041","DOIUrl":"10.1093/mmy/myag041","url":null,"abstract":"<p><p>Candida auris is a multidrug-resistant fungal pathogen responsible for invasive nosocomial infections with high mortality rates. Recent detection of C. auris in natural environments suggests the existence of an environmental reservoir, prompting investigation into the potential role of azole fungicides used for plant protection in the development of resistance to antifungals used in human medicine. Here, we assessed the impact of azole fungicides on in vitro resistance development in two C. auris strains (B11220 and B11221) through sequential exposure to epoxiconazole, propiconazole, or tebuconazole. Exposure resulted in a rapid and significant increase in fungicide MICs, accompanied by a reduced susceptibility to four azole antifungals (fluconazole, voriconazole, posaconazole, isavuconazole), and to a new antifungal agent, the manogepix. Several strains with elevated MICs exhibited stable phenotypes and were associated with a mutation in the TAC1B gene. One of these strains showed a significant overexpression of the efflux pump CDR1. These findings provide experimental evidence that azole fungicides can drive resistance to azole antifungals and reduce susceptibility to manogepix, underscoring the need for integrated One Health antifungal stewardship strategies to combat C. auris.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enyzme immunoassay compared to immunodiffusion complement-fixation to assess the IgG serological response in coccidioidomycosis.","authors":"Chinh T Nguyen, Neil M Ampel","doi":"10.1093/mmy/myag047","DOIUrl":"10.1093/mmy/myag047","url":null,"abstract":"<p><p>Enzyme immunoassay (EIA) is often the initial test performed for diagnosing coccidioidomycosis by serology. When EIA immunoglobulin G (IgG) optical density (OD) positive results were compared to immunodiffusion complement-fixation (IDCF) titer among 339 unique patient samples, there was only moderate correlation (R2 = 0.5345; P < 0.001). In 68 cases (20.1%), the EIA IgG was positive when the IDCF result was negative. When the medical records of 22 patients at one site were reviewed, only 14 (63.6%) with positive EIA IgG tests were associated with clinically active coccidioidomycosis. These results support not using EIA IgG OD as a substitute for CF titer and that an isolated positive EIA IgG may be falsely positive.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Juglone suppresses morphogenesis and early biofilm formation in Candida albicans through disruption of oxidative homeostasis.","authors":"Rama Sameer Obeidat, Homa Darmani","doi":"10.1093/mmy/myag045","DOIUrl":"10.1093/mmy/myag045","url":null,"abstract":"<p><p>Candida albicans is an important opportunistic pathogen causing superficial to life-threatening infections, especially in immunocompromised individuals. Its pathogenicity is largely driven by biofilm formation and phenotypic switching, especially the yeast-to-hypha (germ tube) transition, which plays a crucial role in antifungal tolerance and clinical progression. Despite growing interest in natural antifungals, the role of juglone (5-hydroxy-1,4-naphthoquinone, a natural naphthoquinone derived from Juglans species) in germ tube formation and redox-dependent virulence remains underexplored. This study evaluated juglone's antifungal and anti-virulence effects and whether these involve disruption of oxidative homeostasis. Antifungal activity and virulence-related effects were assessed using MIC/MFC determination, well diffusion, germ tube and biofilm assays, and oxidative stress measurements. Juglone exhibited dose-dependent inhibition of C. albicans growth (MIC = 15.63 µg/ml, MFC = MIC) and an additive interaction with amphotericin B (MIC = 0.39 µg/ml; FICI = 0.5625). Inhibition zones increased in combination, supporting an additive effect. Although effects on mature biofilms, phospholipase, and hemolysin activities were limited, juglone markedly inhibited key virulence factors, reducing germ tube formation to 9% (60% for amphotericin B and 93% control), and suppressing early biofilm formation and extracellular polymeric substance production. Juglone caused only a slight reduction in lactate dehydrogenase release, suggesting membranes remained largely intact, but significantly modulated stress responses by decreasing superoxide dismutase activity and total antioxidant capacity, while malondialdehyde levels remained unchanged, consistent with a redox-based antifungal mechanism. Overall, juglone shows potent antifungal and anti-virulence effects against C. albicans, likely in part by modulating oxidative balance and weakening virulence mechanisms while enhancing conventional antifungal treatment.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jussemara Souza da Silva, Victor Garcia Nuñez, Victória Spínola D de Oliveira, Alessandro C Pasqualotto, José E Vidal
{"title":"Predictors of mortality in individuals with disseminated histoplasmosis and advanced HIV disease.","authors":"Jussemara Souza da Silva, Victor Garcia Nuñez, Victória Spínola D de Oliveira, Alessandro C Pasqualotto, José E Vidal","doi":"10.1093/mmy/myag040","DOIUrl":"10.1093/mmy/myag040","url":null,"abstract":"<p><p>Disseminated histoplasmosis remains a major cause of morbidity and mortality among people living with advanced HIV disease (AHD), particularly in Latin America, where delayed diagnosis and limited access to optimal antifungal therapy persist. Accurate tools to assess disease severity and predict mortality are essential to guide clinical decision-making, including hospitalization, intensive care unit admission, and treatment strategies. We conducted a retrospective observational cohort study of hospitalized adults with AHD (CD4 ≤ 200 cells/mm³) and a first episode of probable or proven disseminated histoplasmosis at a tertiary referral center in São Paulo, Brazil, between 2013 and 2023. Disease severity at admission was assessed using four tools: the World Health Organization (WHO) severity classification, the Histoplasmosis Fatality Score (HFS), the Sequential Organ Failure Assessment (SOFA), and the quick SOFA (qSOFA). The primary outcome was in-hospital mortality. Eighty-nine individuals were included; most were male (77.5%), with a median age of 39 years and profound immunosuppression (median CD4 count 24 cells/mm³). In-hospital mortality was 34.8%. Individuals who died had significantly higher HFS and SOFA scores. In multivariable analysis, HFS, SOFA score, and serum creatinine were independently associated with in-hospital mortality, whereas qSOFA was not. HFS showed the best discriminatory performance (AUC 0.798; 95% CI 0.707-0.889). The combination of HFS and elevated creatinine further improved discrimination (AUC 0.840; 95% CI 0.758-0.922), outperforming the WHO classification, SOFA, and qSOFA in predicting in-hospital mortality. These findings support the use of HFS as a practical and reliable tool for stratifying disease severity, optimizing resource allocation, and guiding clinical decision-making in high-burden settings.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shusaku Suzuki, Masaki Ishii, Shinya Ohata, Yoko Mano, Nobuhiko Furuya
{"title":"Genetic confirmation of terbinafine resistance in Trichophyton rubrum mediated by the squalene epoxidase Leu393Phe mutation via targeted gene replacement.","authors":"Shusaku Suzuki, Masaki Ishii, Shinya Ohata, Yoko Mano, Nobuhiko Furuya","doi":"10.1093/mmy/myag044","DOIUrl":"10.1093/mmy/myag044","url":null,"abstract":"<p><p>Terbinafine (TBF) is a first-line allylamine antifungal used to treat dermatophytosis caused by Trichophyton species, targeting squalene epoxidase (SQLE). The recent emergence of TBF-resistant Trichophyton rubrum (T. rubrum) strains represents a significant global clinical challenge. Although the SQLE Leu393Phe substitution is a commonly reported resistance mechanism in Japan, direct genetic evidence demonstrating its effect when introduced into a T. rubrum recipient strain has been lacking. In this study, we established the causal relationship between the SQLE Leu393Phe substitution and TBF resistance via targeted gene replacement in T. rubrum. A homologous recombination plasmid containing SQLE from the TBF-resistant T. rubrum strain BGUTR13, which harbours the 1177TTA→TTC mutation encoding Leu393Phe, together with the neomycin phosphotransferase II (nptII) selection marker, was constructed and introduced into the TBF-susceptible strain T. rubrum CBS118892 Δku80. The resulting mutant transformants exhibited a > 8000-fold increase in TBF minimum inhibitory concentration compared with the parental strain, whereas control transformants carrying nptII but lacking the SQLE Leu393Phe substitution remained susceptible. Structural modelling indicated that the Leu393Phe substitution causes substantial steric hindrance within the SQLE binding pocket, displacing TBF's aliphatic chain and disrupting key hydrophobic interactions. Molecular docking simulations predicted reduced TBF binding affinity (ΔG changed from -6.3 to -0.8 kcal/mol) following the mutation. These findings provide the first robust genetic evidence that the single SQLE Leu393Phe substitution is sufficient to confer high-level TBF resistance in T. rubrum. These findings highlight the importance of monitoring SQLE mutations in clinical isolates and provide a foundation for developing strategies to address antifungal resistance in dermatophytes.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chia-Yu Chiu, Rachel S Hicklen, Dimitrios P Kontoyiannis
{"title":"Fungal central nervous system infection caused by non-Candida yeasts and dimorphic fungi following neurosurgical procedures: Iatrogenic or not?","authors":"Chia-Yu Chiu, Rachel S Hicklen, Dimitrios P Kontoyiannis","doi":"10.1093/mmy/myag034","DOIUrl":"10.1093/mmy/myag034","url":null,"abstract":"<p><p>Most iatrogenic central nervous system fungal infections (ICNSFIs) are caused by Candida species or molds. However, the ICNSFIs caused by non-Candida yeasts and dimorphic molds have not been evaluated. In the literature review, we identified 24 cases of potential non-Candida yeasts and dimorphic molds-related ICNSFIs, 75% were associated with CNS diversion devices, and 63% were Cryptococcus neoformans infection. The median time from the procedure to the onset of CNS symptoms was 6.5 months. These patients had mild cerebrospinal fluid pleocytosis (median WBC, 12 × 10⁶/l). The 90-day mortality rate was 17%.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lipid-based amphotericin B formulations (ABCD/L-AmB) were associated with better outcomes than deoxycholate (AmB-d) in non-HIV-associated cryptococcal meningitis: A retrospective cohort study.","authors":"Junyu Liu, Jia Liu, Min Li, Ruiqi Dong, Dongcheng Li, Jiajie Chen, Wenhai Zeng, Zheqi Li, Xiaofeng Xu, Ying Jiang, Fuhua Peng","doi":"10.1093/mmy/myag033","DOIUrl":"10.1093/mmy/myag033","url":null,"abstract":"<p><p>This retrospective cohort study compared the efficacy and safety of lipid-based amphotericin B formulations (amphotericin B colloidal dispersion [ABCD] and liposomal amphotericin B [L-AmB]) versus conventional amphotericin B deoxycholate (AmB-d) for the treatment of non-human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM). Data from 199 patients were analyzed, divided into three groups based on induction therapy: AmB-d (n = 110), ABCD (n = 44), and L-AmB (n = 45). At baseline, a higher proportion of patients in the lipid-based groups presented with altered mental status. After 2 weeks, the ABCD and L-AmB groups showed significantly better clinical improvement (as measured by British Medical Research Council Stage 1) compared to the AmB-d group (63.6% and 77.8% vs. 35.5%; P < .001), and experienced substantially lower rates of renal impairment (54.5% and 53.3% vs. 79.1%; P = .001). Early fungicidal activity was similar across all groups. Multivariate analysis at 10 weeks indicated that both lipid-based formulations were associated with a lower risk of unsuccessful outcomes compared to AmB-d. Furthermore, 1-year survival analysis for clinical cure demonstrated a significantly higher cumulative incidence in the lipid-based AmB groups (Log-rank test, P = .016). In conclusion, induction regimens based on ABCD or L-AmB were associated with better outcomes than AmB-d for non-HIV-associated CM, offering better long-term outcomes and a more favorable safety profile, particularly regarding kidney toxicity.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Candidemia caused by Meyerozyma guilliermondii species complex in patients with cancer: A systematic review of case reports.","authors":"","doi":"10.1093/mmy/myag052","DOIUrl":"https://doi.org/10.1093/mmy/myag052","url":null,"abstract":"","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":"64 5","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}