Mycoses最新文献

Background: Azoles target Cyp51A and Cyp51B in Aspergillus fumigatus. Mutations in cyp51A are known as the primary mechanisms of azole resistance. However, not all of them cause azole resistance. Among them, mutations related to improved susceptibility have not been reported so far. We found that two isolates that carry frameshift or nonsense mutations in cyp51A are more susceptible to azoles, even to fluconazole (FLCZ) (IC₅₀: frameshift, 32 μg/mL; nonsense, 32 μg/mL) compared to other azole-susceptible strains (IC₅₀: > 256 μg/mL).

Objectives: We investigated the contribution of these two mutations to azole sensitivity and their effect on Cyp51A functions.

Methods: We transformed an experimental strain, AfS35, by replacing cyp51A^WT with each of the mutated cyp51A and measured its MICs to azoles. We also evaluated the functions of mutated Cyp51A after suppression of Cyp51B, based on the notion that Cyp51A and Cyp51B complement each other.

Results: Induction of mutated cyp51A in AfS35 led to higher susceptibility to FLCZ (IC₅₀: frameshift, 32-64 μg/mL; nonsense, 32 μg/mL). Transformants carrying either of the mutated cyp51A could not survive when cyp51B was suppressed, indicating that these cyp51A mutations result in Cyp51A dysfunction. Furthermore, a cyp51A-deleted mutant strain also showed increased susceptibility to FLCZ (IC₅₀: 32 μg/mL), similar to cyp51A dysfunctional strains, while a cyp51B-deleted mutant strain showed unchanged susceptibility (IC₅₀: > 256 μg/mL) from AfS35.

Conclusions: It was suggested that FLCZ can inhibit Cyp51B rather than Cyp51A and that this unequal inhibition leads to higher azole susceptibility of the two isolates harbouring Cyp51A dysfunction.

Background: Trichophyton indotineae has emerged as a significant global dermatophyte, associated with recalcitrant dermatophytosis and increasing antifungal resistance.

Materials and methods: This study evaluates therapeutic outcomes in T. indotineae infections. We conducted a systematic review and meta-analysis of individual patient data adhering to PRISMA guidelines, including studies published before December 2023 from six electronic databases. Only studies with confirmed T. indotineae by rDNA sequencing and therapeutic outcome data were included.

Results: A total of 27 publications with 81 cases were included. T. indotineae infections affected both genders equally, with 25% having prior steroid use, which was significantly associated with non-improvement. Resistance to terbinafine was observed in 85.3% of cases. Oral itraconazole was significantly associated with a cure. The restricted median time to complete clinical cure was 11.50 weeks, with a recurrence rate of 19.7%.

Conclusions: The effective management of T. indotineae infections is essential, given the significant challenges posed by antifungal resistance.

Background: In mid-2024, German media reported increasing fungal infections by Trichophyton tonsurans linked to visits to barbershops. However, epidemiological data confirming a rise in tinea capitis and tinea corporis due to Trichophyton tonsurans are lacking.

Objectives: This study assesses dermatophyte species and clinical types of infections in German university hospitals in 2018 and 2023.

Patients/methods: This retrospective, multicentre study analyses mycological culture results from three Departments of Dermatology in Freiburg, Tübingen and Munich. The dermatophyte, along with the sampled body site, age and gender of the affected patient, was recorded.

Results: 1915 patients (male: 66.1%; mean age: 50 ± 24 years) with a dermatophyte-positive culture were identified. The most common dermatophyte was Trichophyton rubrum (2018: 78.7%; 2023: 66.3%) with tinea pedis and tinea unguium being the most prevalent types of infection. An increase in tinea corporis and tinea capitis was observed, with tinea capitis doubling from 4.3% to 9.3%. In 2023, Trichophyton tonsurans emerged as the prevailing dermatophyte (67.6%) in tinea capitis and as the second most frequent agent in tinea corporis (26.3%). This dominance of Trichophyton tonsurans was consistently observed across all three study centres. Trichophyton tonsurans affected patients presented a median age of 18 years in 2023 (vs. 9 years in 2018) and an amplified imbalance towards the male gender.

Conclusions: The pathogen spectrum and infection patterns have changed in Germany due to the increase of Trichophyton tonsurans infections. Intensified screening and hygiene measures, as well as adaptation of initial empiric treatment of tinea capitis, should be considered.

Background: In 2019, Trichophyton mentagrophytes genotype VII (TMVII) was identified in Germany as a cause of sexually transmitted tinea. Since 2023, it has been described in men who have sex with men (MSM) in France, Italy, and the United States. No cases have been reported in Spain.

Obectives: Our study aimed to assess the occurrence of TMVII in an STI clinic in Barcelona.

Patients/methods: We identified TMVII cases among all positive mycological skin/hair cultures between January 2020 and January 2025 by sequencing the internal transcribed spacer on isolates of T. mentagrophytes-interdigitale. We retrospectively collected demographic, clinical and treatment data and analysed the association between treatment received and outcome (cure vs. recurrence).

Results: Among 21 positive cultures, we obtained 15 isolates of T. mentagrophytes-interdigitale, of which 14 were sequenced and identified as TMVII. Patients with TMVII were all MSM; most were HIV positive (7) or negative on preexposure prophylaxis (6). Main sites of infection were pubogenital (6), buttocks-perianal (5) and beard (2). Six patients required multiple courses of treatment due to recurrence. Twenty-one courses of antifungal therapy were analysed, with an observed cure rate of 45% (5/11) for oral terbinafine vs. 80% (7/10) for topical agents (p = 0.39), and 0% (0/6) for ≤ 2-week courses vs. 80% (12/15) for 3-to-8-week courses (p < 0.01).

Conclusions: Our study confirms the presence of TMVII in Spain, supporting its circulation across Europe. Epidemiological profile and site of infection support sexual transmission. Patients responded to systemic or topical terbinafine but required longer-than-usual periods of treatment.

Candida auris (C. auris) is a therapeutic challenge due to the lack of definition of susceptibility breakpoints and the misidentification by biochemical tests, which leads to suboptimal therapy. Hence, our goal was to assess the treatment outcomes of C. auris infections at our institution.

Methods: A retrospective observational study between January 2019 and June 2022 that included confirmed C. auris infection cases. The primary endpoint was to assess the clinical outcomes of C. auris management. The secondary endpoints were to evaluate mycologic cure, 30 and 90-day infection recurrence, and 30-day all-cause mortality. Descriptive statistics were used to analyse our data.

Results: Fifty-six subjects were evaluated, with a mean age of 65.05 ± 16.86 years. Candidemia accounted for 62.7% of cases. Clinical cure was achieved in 57% of patients, and mycologic cure in 84.4%. Recurrence of C. auris infection occurred in 28.6% at 30 days and in 12.7% at 90 days. Thirty-day all-cause mortality occurred in 28.6% of patients. Multivariable logistic regression indicated that mycologic cure with Odds Ratio (OR) 6.96 (95% CI: 1.21-39.92), length in intensive care units (ICU) stay OR 0.132 (95% CI: 0.019-0.907), and baseline C-reactive protein (CRP) OR 0.990 (95% CI: 0.982-0.998) were the independent predictors of clinical cure.

Conclusion: Clinical cure of invasive C. auris infections was dependent on mycologic cure, length of ICU stays, and baseline CRP levels, with observed 30-day all-cause mortality up to 28.6%. Similarly to other reports, our isolates exhibited resistance to fluconazole and amphotericin B in most cases. Only two isolates demonstrated resistance to caspofungin and were deemed pan-resistant. Further multi-centre studies are needed to validate our findings.

Background: The Trichophyton mentagrophytes complex encompasses common dermatophytes causing superficial mycoses in humans and animals. The taxonomy of the complex is unstable, with conflicting views on the species status of some taxa, particularly T. indotineae and T. interdigitale. Due to the presence of intermediate genotypes, neither MALDI-TOF MS nor ITS rDNA sequencing can accurately distinguish all taxa in the complex, potentially contributing to clinical misdiagnoses.

Objectives: This research resolves phylogenetic relationships within the T. mentagrophytes complex. Based on these data, the taxonomical recommendations are suggested.

Methods: In order to resolve the phylogenetic relationship of the T. mentagrophytes complex, we employed Restriction Site-Associated DNA Sequencing (RADseq) to produce a high-resolution single nucleotide polymorphism (SNP) dataset from 95 isolates. The SNP-based analyses indicated the presence of two major genetic clusters corresponding to T. mentagrophytes (including T. indotineae) and T. interdigitale.

Results: Our results challenge the species status of T. indotineae because of insufficient genetic divergence from T. mentagrophytes. Therefore, we propose designating T. indotineae as T. mentagrophytes var. indotineae (or T. mentagrophytes ITS genotype VIII) to avoid further splitting of the complex and taxonomic inflation. Although T. interdigitale shows clearer genetic differentiation, its separation is incomplete and identification of some isolates is ambiguous when using routine methods, leading us to consider it a variety as well: T. mentagrophytes var. interdigitale.

Conclusions: We recommend using T. mentagrophytes as the overarching species name for all complex isolates. Where precise molecular identification is possible, the use of variety ranks is encouraged. Since identical resistance mechanisms are not specific to any genotype or dermatophyte species, identifying antifungal resistance is more important than differentiating closely related genotypes or populations.

Background: Trichophyton rubrum is one of the most common human pathogenic fungi, with the infections often managed through empirical drug use. However, treatments frequently lead to relapse upon withdrawal. The rise in drug-resistant T. rubrum cases has led to an increased demand for drug susceptibility assays in clinical settings to guide antifungal drug selection and monitor therapeutic outcomes. However, insufficient sporulation of T. rubrum on routinely-used media presents a significant challenge, limiting the widespread use of drug sensitivity tests on a large scale.

Objectives: There is an urgent need to develop a new, effective culture method that can promote rapid and abundant sporulation of T. rubrum.

Methods: In this study, we adopted a nutrient-rich medium (Yeast extract-glucose YAG) which demonstrated superior efficacy in promoting T. rubrum sporulation compared to PDA and OA mediums.

Results: Abundant microconidia production of T. rubrum was observed at 30° between 7 to 10 days on YAG medium, and this sporulation was further enhanced under elevated carbon dioxide conditions. Particularly, a 20% carbon dioxide environment significantly improved T. rubrum sporulation on PDA by 30-fold, equivalent to the sporulation effect with YAG cultivation.

Conclusions: This enhanced sporulation was confirmed in 37 clinical T. rubrum isolates, highlighting the potential applicability of YAG medium in both clinical and research settings for drug susceptibility assays and pathogenesis studies. These findings also offer new insights into improving sporulation in other fungi with low spore production.

Background: Candida auris is an emerging fungal pathogen that is often multidrug-resistant. It can persist on skin and in hospital environments, leading to outbreaks and severe infections for patients at risk. Several countries and institutions are working on establishing guidelines and recommendations for prevention. This review aims to assess the evidence on factors associated with C. auris colonisation or infection, the duration of such colonisation, possible colonisation sites, and the risk of secondary cases to inform screening recommendations.

Methods: We systematically searched five databases for primary studies and systematic reviews of our four outcomes. We excluded studies on treatment, management, laboratory methods, drug resistance, and environmental screening. From each paper, we extracted relevant data and summarised them in tables. Main findings were described narratively.

Findings: We selected 117 studies for inclusion. Most of the studies were observational studies. Without taking the method of testing into account, the duration of C. auris colonisation varied, with up to and beyond a year being common. The predominant sites of colonisation were the axillae and groin, with the nares and rectum being less common sites. The risk of secondary cases saw considerable variation across the studies, and the secondary cases primarily involved patients and not healthcare workers. Critical care settings, invasive medical devices, recent antimicrobial use, and comorbidities were often associated with C. auris colonisation and infection.

Conclusion: Our review highlights that, despite relevant findings on factors influencing C. auris colonisation and infection, substantial gaps remain in the evidence supporting screening practices. Most studies were conducted reactively, in outbreak settings, and lack systematic protocols. Given these limitations, screening guidelines are likely to be more successful if grounded in medical theory and yeast microbiology rather than relying solely on current studies. Rigorous, well-designed research is urgently needed to inform future C. auris screening and control efforts.

TNF-α inhibitors, including infliximab, adalimumab and etanercept, are used to treat various inflammatory diseases, such as arthritis, psoriasis and ankylosing spondylitis. However, these treatments may predispose patients to fungal infections, including histoplasmosis, candidiasis and aspergillosis. In this study, we systematically reviewed case reports to critically examine the correlations between anti-TNF-α therapies and the occurrence of invasive and superficial fungal infections. Infliximab was the most commonly used TNF-α inhibitor (50.65%). The highest number of fungal infections during anti-TNF34 α therapy was reported in the USA (84.25%). The conditions treated primarily included rheumatoid arthritis. A total of 517 invasive fungal infections were identified, including histoplasmosis, invasive candidiasis and aspergillosis, with histoplasmosis being the most common. Most studies were conducted in higher-income countries, highlighting the critical lack of research on the use of immunobiologicals in relation to fungal diseases in African countries, which requires further attention. Logistic regression analysis revealed significant associations between adalimumab use and increased risks of candidiasis, coccidioidomycosis, onychomycosis and pityriasis versicolor. For etanercept, significant associations were found with aspergillosis, coccidioidomycosis, cryptococcosis, dermatophytosis, invasive candidiasis, pityriasis versicolor and onychomycosis. Infliximab use was significantly associated with coccidioidomycosis, onychomycosis, aspergillosis, cryptococcosis, histoplasmosis and invasive candidiasis. The data presented in this study clearly demonstrate an association between the use of TNF-α inhibitors and an increased risk of fungal infections. It is imperative that healthcare professionals maintain a high level of vigilance when managing patients on these medications. Regular monitoring and proactive management strategies are essential to mitigate risks and ensure patient safety.

Background: Mucormycosis is a life-threatening fungal infection with high mortality in critically ill patients. Clinical manifestations and outcomes of mucormycosis in intensive care units (ICUs) remain poorly investigated.

Methods: We conducted a multicenter retrospective study including 43 adult patients with confirmed mucormycosis admitted to 14 tertiary ICUs between January 2014 and May 2022. Clinical characteristics, diagnostic approaches, treatment strategies, and outcomes were analysed.

Results: The mean age was 56.8 ± 16.2 years, with 16/43 (37.2%) female patients. The 28-day survival rate was 46.5% (20/43). Lung involvement was predominant (29/43, 67.4%), and 29/43 (67.4%) patients received amphotericin B therapy. Survivors showed significantly better treatment response compared to non-survivors (16/20, 80% vs. 4/23, 17.4%, p < 0.001). Non-survivors demonstrated significantly higher levels of aspartate aminotransferase, C-reactive protein, and white blood cells, along with lower albumin levels. Metagenomic next-generation sequencing (mNGS) was associated with a shorter time to diagnosis. Multivariate analysis identified age, respiratory failure, time from symptom onset to diagnosis, and antifungal treatment response as independent predictors of 28-day mortality (AUC = 0.852).

Conclusion: In critically ill patients with mucormycosis, early diagnosis and prompt targeted therapy are crucial determinants of survival, with our newly developed prediction model providing a practical tool for risk stratification, while mNGS shows promise in expediting diagnosis.