Mycoses最新文献

Background: Terbinafine resistance in dermatophytes is an increasing problem worldwide. Several outbreaks of terbinafine-resistant dermatophytosis are currently occurring in India and surrounding countries, and these recent years, European countries have also been affected by this issue. Currently, antifungal susceptibility testing of dermatophytes is not routinely performed in clinical laboratories.

Objectives: Given the current situation and associated public health concerns, there is an urgent need for accurate and rapid detection of terbinafine resistance in laboratories. Therefore, we evaluated different methods currently available for the detection of terbinafine resistance in dermatophytes.

Methods: Twenty-eight strains previously identified as T. indotineae/mentagrophytes/interdigitale were concurrently characterised using terbinafine gradient strips (HiMedia), EUCAST E.Def 11.0 microdilution, the DermaGenius resistance PCR assay (PathoNostics), and SQLE sequencing. These four methods were compared to terbinafine resistance characterisation obtained by whole genome sequencing (WGS).

Results: All four evaluated methods were able to detect terbinafine resistant strains either by showing high MICs (> 0.125 μg/mL) or by detecting SQLE substitutions.

Conclusions: The gradient strips, despite questionable essential agreement with EUCAST E.Def 11.0, can be an easy, fast and cheap method to screen terbinafine resistance among dermatophytes in clinical laboratories. The DermaGenius resistance PCR assay enables rapid detection of the most common substitutions in SQLE associated with terbinafine resistance. However, its inability to precisely determine specific substitutions on SQLE or identify new ones may pose a problem in the future. These limitations can be addressed by using SQLE sequencing or whole genome sequencing (WGS).

Background: Trichophyton indotineae, a newly defined species within the T. mentagrophytes/T. interdigitale complex, has emerged as an epidemiological concern worldwide. However, owing to the limitations of commonly applied fungal identification techniques, T. indotineae remains underreported. In addition, T. indotineae's response to treatment has been described in only a few studies.

Objective: To investigate the prevalence, clinical characteristics and treatment outcomes of terbinafine-resistant T. mentagrophytes/T. interdigitale complex infections, as well as to detect T. indotineae cases.

Patients and methods: A retrospective cohort study was conducted on 22 patients with T. mentagrophytes/T. interdigitale complex infections between 2019 and 2023, using either culture or commercial polymerase chain reaction methods. Patient demographics, disease characteristics and treatment responses were recorded. Patients non-responsive to oral terbinafine underwent further analyses, including DNA sequencing of the internal transcribed spacer region for accurate species identification and mutational analysis of the squalene epoxidase (SQLE) gene.

Results: The mean age of the patients was 49.7 years (±18.2), with 54.5% men. Terbinafine-resistant T. mentagrophytes/T. interdigitale complex infections were reported in 46.2% of the cohort (n = 6/13 patients; 9 lost to treatment response follow-up), all of whom exhibited extensive dermatophytosis. Among the terbinafine-resistant T. mentagrophytes/T. interdigitale isolates, all five isolates available for fungal analysis were identified as T. indotineae, harbouring SQLE single-point mutations (Phe397Leu and Leu393Ser). Only three of the terbinafine-resistant cases responded to oral itraconazole 200 mg/day, with two responding only to oral voriconazole and one to oral itraconazole 400 mg/day.

Conclusion: All cases of T. mentagrophytes/T. interdigitale assessed in this study were identified as T. indotineae, which exhibits SQLE gene mutations. This underscores the importance of integrating methods to detect T. indotineae in routine clinical practice.

Objectives: Worldwide emergence of clonal outbreaks caused by fluconazole-resistant (FLCR) and the recent emergence of echinocandin- and multidrug-resistant (ECR and MDR) Candida parapsilosis isolates pose serious threats to modern clinics. Conducting large-scale epidemiological studies aimed at determining the genetic composition and antifungal resistance rates is necessary to devise antifungal stewardship and infection control strategies at international, national and local levels. Despite being severely hit by outbreaks due to FLCR C. parapsilosis isolates, such knowledge at the national level is lacking in Türkiye. Herein, we conducted a prospective multicentre study involving five major clinical centres in Türkiye to determine antifungal resistance rates, underlying mechanisms and genetic composition of all isolates.

Methods: In total, 341 isolates were collected from 265 patients including clinical information. Antifungal susceptibility testing against common antifungals was performed in addition to sequencing of ERG11 and FKS1. Last, isolates were genotyped with short tandem repeat (STR) genotyping to investigate potential nosocomial transmission.

Results: The FLCR rate was 26.7% (91/341), out of which 75.8% (69/91) harboured the ERG11^Y132F mutation. Patients infected with FLCR isolates had a higher mortality rate compared to their susceptible counterparts (49% for FLCR vs. 42% for susceptible). ECR rate was 2.1% (7/341) and isolates carried FKS1^{F652L/R658G/W1370R} mutations. Concerningly, four ECR isolates were MDR. FLCR isolates grouped in distinct clusters without evidence of inter-hospital transmission, whereas large clusters containing susceptible isolates from all centres were noted.

Conclusion: Overall, the increasing prevalence of FLCR C. parapsilosis at national level and the emergence of ECR and MDR isolates pose serious clinical challenges in Türkiye. Therefore, conducting large-scale epidemiological studies are critical to determine the trend of antifungal resistance and to tailor pertinent antifungal stewardship and infection control strategies to effectively curb the spread of drug-resistant C. parapsilosis.

Background: Candida parapsilosis is a pathogenic yeast that has reduced susceptibility to echinocandins and ranks as the second or third leading cause of candidaemia, depending on the geographical region. This yeast often causes nosocomial infections, which are frequently detected as outbreaks. In recent years, resistance to azoles in C. parapsilosis has increased globally, primarily due to the accumulation of mutations in the ERG11 gene.

Objectives: In this study, we have developed an assay based on real-time PCR and high-resolution melting (HRM) curve analysis to detect two of the most prevalent mutations at ERG11 that confer resistance to fluconazole (Y132F and G458S).

Methods: We designed allele-specific oligonucleotides that selectively bind to either the wild type or mutated sequences and optimised the conditions to ensure amplification of the specific allele, followed by detection via high-resolution melting (HRM) analysis.

Results: The designed oligonucleotides to detect the Erg11^Y132F and Erg11^G458S mutations produced specific amplification of either WT or mutated alleles. We conducted a duplex real-time PCR combining oligonucleotides for the wild-type sequences in one mix, and oligonucleotides for the mutated alleles in another. Following this, we performed an analysis of the HRM curve to identify the amplified allele in each case. This technique was blindly evaluated on a set of 114 C. parapsilosis isolates, all of which were unequivocally identified using our approach.

Conclusion: This technique offers a new method for the early detection of azole resistance mechanism in C. parapsilosis.

Background: Invasive candidiasis (IC) is increasing due to the rising numbers of immunocompromised patients. Increasing azole resistance rates and daily dosing required for most echinocandins have complicated its treatment. The approval of rezafungin has provided an option for weekly echinocandin treatment. The susceptibility of less common Candida spp. to rezafungin is unclear. We looked at the minimum inhibitory concentrations (MICs) of rezafungin and comparator agents against Candida spp. collected as part of a global surveillance program.

Method: The CLSI reference broth microdilution method was performed to test 590 clinical isolates of 28 different Candida species, including Candida auris. Species-specific interpretative criteria by breakpoints or epidemiological cutoff values were applied where available.

Results: Rezafungin was within ±2-fold MIC₅₀/₉₀ values of other echinocandins against all Candida spp. The lowest rezafungin MIC₅₀/₉₀ values were noted against C. kefyr (0.03/0.06 mg/L) and C. pelliculosa (0.015/0.03 mg/L). Higher rezafungin MIC₅₀/₉₀ values were noted for C. guilliermondii (1/1 mg/L) and for isolates in the C. parapsilosis complex (C. orthopsilosis, 0.5/1 mg/L, C. metapsilosis, 0.12/0.5 mg/L). Rezafungin was active against 97.7% of C. dubliniensis and 95.4% of C. auris by CLSI breakpoints. For fluconazole, 69.7% of C. guilliermondii, 85.7% of C. orthopsilosis, and 100% of C. metapsilosis were wildtype by ECV, and 10.8% of C. auris were susceptible by CDC breakpoint.

Conclusions: Rezafungin was highly active by in vitro testing against less common Candida spp. Rezafungin MICs were comparable to other echinocandins. Rezafungin is a desirable therapeutic alternative due to its reduced dosing frequency.

Background: Previous studies correlated Sensititre YeastOne and gradient diffusion plastic strips with standard procedures for the detection of echinocandin-resistant C. glabrata isolates. However, these studies were limited by the low number of resistant isolates studied; the inclusion of sufficient numbers of mutant isolates is essential to test the procedures' capacity to detect resistance.

Objective: We assessed the performance of Sensititre YeastOne and Etest strips to detect echinocandin resistance in susceptible or resistant C. glabrata isolates (n = 80) in which the FKS genes were sequenced, and MICs interpreted using EUCAST and CLSI breakpoints.

Patients/methods: Isolates were echinocandin-susceptible (n = 50) or echinocandin-resistant according to EUCAST 7.4 methodology. Echinocandin susceptibility using Sensititre YeastOne and Etest strips and categorical agreement were assessed.

Results: All except one anidulafungin-resistant isolate had an anidulafungin Sensititre YeastOne MIC ≥ 0.25 mg/L, while most micafungin-resistant isolates had a MIC ≥ 0.25 mg/L. Likewise, all anidulafungin-resistant isolates had an anidulafungin Etest strip-obtained MIC ≥ 0.03 mg/L, whereas micafungin-resistant isolates were ≥ 0.125 mg/L. Overall, these commercial methods correctly classified > 90% of isolates by using any breakpoint. Despite the low number of errors detected, these were mostly false resistance (major errors) with EUCAST breakpoints and false susceptibility (very major errors) with CLSI breakpoints.

Conclusions: Sensititre YeastOne and Etest strips were suitable procedures to detect echinocandin resistance in C. glabrata. The high number of FKS mutants included reinforces our study and opens the door for multicentre validations.

Background: Dermatophytosis, caused by dermatophytes, affects up to 25% of people globally, with higher rates observed in Africa and Asia. While these infections are usually superficial, they can become severe in immunocompromised individuals. Despite their high prevalence, scientific research on dermatophytes is limited and the epidemiological data available are insufficient. In addition, diagnostic methods are not standardised and there are challenges with resistance to antifungals.

Objectives: This study aimed to conduct a bibliometric analysis of scientific publications related to dermatophytes and dermatophytosis to assess research output and trends.

Methods: A bibliometric analysis of publications from 2000 to 2023 in Web of Science and Scopus examined trends, citation counts, publication types, key journals, top authors and institutions and funding sources.

Results: The analysis revealed a significant increase in dermatophyte-related publications, with 15,868 articles retrieved from the Web of Science and 23,189 from Scopus. Research articles dominated the output, constituting 76.2% in Web of Science and 80% in Scopus. Peak publication years were 2019, 2021 and 2022 in Web of Science, and 2020, 2021 and 2023 in Scopus, with lower output between 2000 and 2002. The United States and India were the leading contributors, followed by Brazil and China, though citation metrics varied. Although there has been a rise in the number of publications, the amount of research conducted on dermatophytes is still very limited in comparison with other types of fungal diseases.

Conclusions: Dermatophyte-related research has increased over the past 2 decades. However, research gaps remain, particularly compared with other fungal diseases. Advances in diagnostics, antifungal testing and taxonomic classification are urgently needed. The study underscores the need for continued research and global collaboration to address these issues.

Tropicoporus tropicalis (formerly Phellinus tropicalis) is a saprophytic basidiomycete that has been implicated in refractory mycoses in humans, particularly in patients with chronic granulomatous disease. Despite its clinical significance, T. tropicalis is an under-recognised cause of eumycetoma, with no prior reports available. We present a case of white grain eumycetoma with associated osteomyelitis of the left foot, caused by T. tropicalis, confirmed through 18S-ITS1-5.8S-ITS2-28S rRNA gene amplification and sequencing. The patient was treated with itraconazole 200 mg daily, leading to gradual improvement. A review of the literature on T. tropicalis infections in humans reveals its characteristic manifestations, which include osteomyelitis, soft tissue abscesses, pulmonary nodules and keratitis. These infections are locally destructive but have the potential to disseminate. Diagnosis is often delayed and relies on molecular techniques. Amphotericin B combined with an azole appears to be the most effective treatment, often necessitating concurrent surgical drainage. In conclusion, T. tropicalis is a newly recognised pathogen associated with eumycetoma and poses an increased risk of osteomyelitis. Molecular identification, such as sequencing the internal transcribed spacer (ITS) region from cultures or tissue specimens, is crucial for accurate identification of this pathogen.

Sporotrichosis is a disease that arises from a fungal infection caused by members of the Ascomycete genus Sporothrix. The disease has a unique history in South Africa, due to an association with gold mines, where large numbers of mine workers were infected in the 1930s and 1940s. This was likely driven by hot humid conditions and timber supports used in these mine shafts. Furthermore, the disease is the most common subcutaneous fungal infection amongst the general population in South Africa, and the large number of immunocompromised individuals increases the public health risk in the country. Sporothrix is a genus in the Ophiostomatales, a fungal order primarily associated with environmental habitats. Unsurprisingly, sporotrichosis therefore has a documented history of sapronotic transmission from contaminated plant material. This review provides insights into the understanding of sporotrichosis and Sporothrix species, with a particular emphasis on the South African situation. We highlight knowledge gaps, particularly regarding the ecological factors influencing the occurrence and distribution of these species, which in turn affect the patterns of sporotrichosis. We also emphasise a need for ongoing proactive research and surveillance to prevent future outbreaks of sporotrichosis, an emerging disease with growing health implications worldwide.

Rationale: The epidemiology and clinical impact of COVID-19-associated candidemia (CAC) remained uncertain, leaving gaps in understanding its prevalence, risk factors and outcomes.

Methods: A systematic review and meta-analysis were conducted by searching PubMed, Embase and Scopus for reports of CAC prevalence, risk factors and clinical outcomes up to June 18, 2024. The generalised linear mixed model was employed to determine the prevalence and 95% confidence intervals (CIs). The risk factors and clinical outcomes were compared between patients with and without CAC using the inverse variance method.

Results: From 81 studies encompassing 29 countries and involving 351,268 patients, the global prevalence of CAC was 4.33% (95% Cl, 3.16%-5.90%) in intensive care unit (ICU) patients. In ICUs, the pooled prevalence of CAC in high-income countries was significantly higher than that of lower-middle-income countries (5.99% [95% Cl, 4.24%-8.40%] vs. 2.23% [95% Cl, 1.06%-4.61%], p = 0.02). Resistant Candida species, including C. auris, C. glabrata (Nakaseomyces glabratus) and C. krusei (Pichia kudriavzveii), constituted 2% of ICU cases. The mortality rate for CAC was 68.40% (95% Cl, 61.86%-74.28%) among ICU patients. Several risk factors were associated with CAC, including antibiotic use, central venous catheter placement, dialysis, mechanical ventilation, tocilizumab, extracorporeal membrane oxygenation and total parenteral nutrition. Notably, the pooled odds ratio of tocilizumab was 2.59 (95% CI, 1.44-4.65).

Conclusions: The prevalence of CAC is substantial in the ICU setting, particularly in high-income countries. Several risk factors associated with CAC were identified, including several that are modifiable, offering the opportunity to mitigate the risk of CAC.