Mycoses最新文献

{"title":"Sporothrix and Sporotrichosis: A South African Perspective on a Growing Global Health Threat.","authors":"Taygen Fuchs, Cobus M Visagie, Brenda D Wingfield, Michael J Wingfield","doi":"10.1111/myc.13806","DOIUrl":"https://doi.org/10.1111/myc.13806","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18797,"journal":{"name":"Mycoses","volume":"67 10","pages":"e13806"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Candidemia Following Severe COVID-19 in Hospitalised and Critical Ill Patients: A Systematic Review and Meta-Analysis.","authors":"Karan Srisurapanont, Bhoowit Lerttiendamrong, Tanaporn Meejun, Jaedvara Thanakitcharu, Kasama Manothummetha, Achitpol Thongkam, Nipat Chuleerarux, Anawin Sanguankeo, Lucy X Li, Surachai Leksuwankun, Nattapong Langsiri, Pattama Torvorapanit, Navaporn Worasilchai, Rongpong Plongla, Chatphatai Moonla, Saman Nematollahi, Olivia S Kates, Nitipong Permpalung","doi":"10.1111/myc.13798","DOIUrl":"10.1111/myc.13798","url":null,"abstract":"<p><strong>Rationale: </strong>The epidemiology and clinical impact of COVID-19-associated candidemia (CAC) remained uncertain, leaving gaps in understanding its prevalence, risk factors and outcomes.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":18797,"journal":{"name":"Mycoses","volume":"67 10","pages":"e13798"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EQUAL ABPA Score 2024: A Tool to Measure Guideline Adherence for Managing Allergic Bronchopulmonary Aspergillosis.","authors":"Inderpaul Singh Sehgal, Valliappan Muthu, Danila Seidel, Rosanne Sprute, Darius Armstrong-James, Koichiro Asano, James D Chalmers, Jean-Pierre Gangneux, Cendrine Godet, Helmut J F Salzer, Oliver A Cornely, Ritesh Agarwal","doi":"10.1111/myc.13810","DOIUrl":"https://doi.org/10.1111/myc.13810","url":null,"abstract":"<p><strong>Objectives: </strong>Allergic bronchopulmonary aspergillosis (ABPA) is a complex lung disease associated with significant morbidity. The ABPA Working Group (AWG) of the International Society for Human and Animal Mycology (ISHAM) revised their management guidelines in 2024, but there is currently no standardised tool to assess adherence to these recommendations.</p><p><strong>Methods: </strong>We extracted key recommendations from the updated 2024 ISHAM-AWG guidelines, focusing on critical areas: screening and diagnosis of ABPA, managing acute and treatment-dependent ABPA, and monitoring treatment response. Each item was assigned a score ranging from zero to three. We assigned negative scores to interventions not recommended by the guidelines.</p><p><strong>Results: </strong>We identified 38 items indicative of optimal clinical care for patients with ABPA. The score for screening asthmatics for ABPA was set at three points. For diagnosing ABPA, 16 items were included, with a score ranging from 12 to 16 points, depending on the specific components used (predisposing conditions, serum A. fumigatus-specific IgE and IgG, serum total IgE, blood eosinophil count and chest computed tomography). The management of acute ABPA comprised 11 items, with a maximum score of three points. For treatment-dependent ABPA, there were nine items (scores ranging from -3 to 6). Follow-up care comprised 10 items with a maximum score of 10-13 points, covering imaging, spirometry, testing serum total IgE levels and therapeutic drug monitoring.</p><p><strong>Conclusions: </strong>The EQUAL ABPA score has been developed as a comprehensive tool to quantify guideline adherence. Future studies will evaluate to which extent guideline adherence is associated with improved clinical outcomes for patients with ABPA.</p>","PeriodicalId":18797,"journal":{"name":"Mycoses","volume":"67 10","pages":"e13810"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intra-Abdominal Candidiasis in Cancer Patients: A 10-Year Experience in a Middle-Income Country.","authors":"Bianca Leal de Almeida, Vitor Ciampone Arcieri, Danilo Mardegam Razente, Maristela Pinheiro Freire, Thais Guimarães, Evangelina da Motta Pacheco Alves de Araújo, Edson Abdala, Marcello Mihailenko Chaves Magri","doi":"10.1111/myc.13807","DOIUrl":"https://doi.org/10.1111/myc.13807","url":null,"abstract":"<p><strong>Background: </strong>Invasive candidiasis (IC) represents a significant threat to both mortality and morbidity, especially among vulnerable populations. Intra-abdominal candidiasis (IAC) frequently occurs in critically ill and cancer patients, with these specific groups carrying a heightened risk for such invasive fungal infections. Despite this, there is a noticeable lack of attention to IAC in cancer patients within the literature, highlighting a critical gap that requires urgent consideration.</p><p><strong>Objectives: </strong>This study aimed to explore the clinical and epidemiological characteristics of IAC and identify prognostic factors in a cancer centre in a middle-income country over 10 years.</p><p><strong>Patients/methods: </strong>A retrospective cohort observational study of adults diagnosed with IAC was conducted at the Instituto do Cancer do Estado de São Paulo (ICESP), a tertiary hospital specialising in oncological diseases with 499 beds, including 85 intensive care unit (ICU) beds, from December 2009 through May 2021.</p><p><strong>Results: </strong>A total of 128 episodes were included: 67.2% admitted to the ICU; 54.7% males; and median age 62 years. The predominant diagnosis was peritonitis (75.8%). Blood culture samples were collected from 128 patients upon admission, revealing candidemia in 17.2% (22). The most frequently isolated were C. albicans (n = 65, 50.8%) and C. glabrata (n = 42, 32.8%). Antifungal treatment was administered to 91 (71%) patients, with fluconazole (64.8%) and echinocandins (23.4%) being the most common choices. A significant proportion of these patients had a history of abdominal surgery or antibiotic use. Independent factors associated with 30-day mortality included the median Sequential Organ Failure Assessment (SOFA) score of 6 (OR = 1.30, 95% CI 1.094-1.562, p = 0.003), days of treatment (median 10.5) (OR = 0.93, 95% CI 0.870-0.993, p = 0.031) and abdominal source control (78.1%) (OR = 0.148, 95% CI 0.030-0.719, p = 0.018). The 30-day mortality rate was 41.1%.</p><p><strong>Conclusions: </strong>Our study underscores the critical importance of implementing effective source control as a key strategy for reducing mortality in IAC.</p>","PeriodicalId":18797,"journal":{"name":"Mycoses","volume":"67 10","pages":"e13807"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fungal Intracranial Infections (Central Nervous System-Invasive Fungal Disease) in Patients With Haematological Disorders-A Single-Centre Retrospective Study.","authors":"Sohini Chattopadhyay, Lydia Jennifer Sumanth, Harshad Arvind Vanjare, Sharon Anbumalar Lionel, Sushil Selvarajan, Uday Kulkarni, Fouzia N Abubacker, Kavitha M Lakshmi, Anu Korula, Aby Abraham, Vikram Mathews, Joy Sarojini Michael, Biju George","doi":"10.1111/myc.13809","DOIUrl":"https://doi.org/10.1111/myc.13809","url":null,"abstract":"<p><strong>Background: </strong>Invasive fungal disease (IFD) is a sinister complication encountered in patients with haematological disorders. When occurring in the central nervous system (CNS), IFDs can have catastrophic outcomes.</p><p><strong>Objectives: </strong>To study the clinical presentation, predisposing etiological factors, and prognosis of a CNS-IFD in a patient with a haematological disorder.</p><p><strong>Patients and methods: </strong>This is a retrospective study focusing on the clinical profile, diagnosis, treatment strategy and outcomes of 43 patients with an underlying haematological disorder, who were diagnosed with CNS-IFD between 2018 and 2022.</p><p><strong>Results: </strong>Of the 43 patients, 18 were chemotherapy recipients, while 23 were stem cell transplant (SCT) recipients and 2 presented with CNS-IFD at diagnosis. AML/MDS (37.2%) and ALL (18.6%) were the predominant underlying diagnoses. A sudden deterioration in sensorium (53.5%) was the earliest clinical sign, while T2 hyperintensities (26.8%), vascular involvement (26.8%) and ring-enhancing lesions (16.3%) were the commonest radiological findings, with all patients exhibiting diffusion restriction in diffusion-weighted images. Microbiological evidence of infection was obtained in all patients; however, culture positivity was established in only 25 patients. Rhizopus spp (23.2%) and Aspergillus spp (20.9%) were implicated in most cases. Overall survival of the cohort was 27.9% at a median follow-up of 6 months. In patients who succumbed, the median time to death was 4 days (0-46).</p><p><strong>Conclusion: </strong>CNS-IFD is associated with very poor survival in patients undergoing chemotherapy or an SCT, urging the need for prompt diagnosis and initiation of suitable antifungal therapy.</p>","PeriodicalId":18797,"journal":{"name":"Mycoses","volume":"67 10","pages":"e13809"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neglected Pulmonary Infection Caused by Exophiala dermatitidis Misidentified as Rhodotorula spp.","authors":"Daichi Setoguchi, Naoki Iwanaga, Yuya Ito, Tatsuro Hirayama, Masataka Yoshida, Kazuaki Takeda, Shotaro Ide, Shinnosuke Takemoto, Masato Tashiro, Naoki Hosogaya, Takahiro Takazono, Kosuke Kosai, Hiroshi Ishimoto, Noriho Sakamoto, Yasushi Obase, Tomoya Nishino, Koichi Izumikawa, Katsunori Yanagihara, Hiroshi Mukae","doi":"10.1111/myc.13804","DOIUrl":"10.1111/myc.13804","url":null,"abstract":"<p><p>Exophiala dermatitidis is an emerging black fungus that causes pulmonary infections that may be underestimated by conventional culture methods. We encountered one case that initially appeared to be yeast and was misidentified as Rhodotorula spp. using a commercial identification kit. Thus, genetic identification and clinical background investigations were conducted on 46 strains of Rhodotorula spp. The sequences of the internal transcribed spacer and large-subunit RNA genes (D1/D2 regions) of 43 isolates, excluding two environmental isolates and one difficult-to-culture isolate, were determined and genetically identified. Notably, 22 isolates were identified as E. dermatitidis and misidentified as Rhodotorula spp. using the conventional method. Based on the exclusion criteria, the clinical information of 11 patients was retrospectively reviewed. Five cases (definite) had definite exacerbation of pulmonary infections due to E. dermatitidis, and six cases (possible) had undeniable infections. Of the 11 cases of pulmonary infection suggested to be caused by E. dermatitidis, comorbidities included two cases of chronic pulmonary aspergillosis (CPA), three cases of pulmonary non-tuberculous mycobacterial (NTM) infection and one case of pulmonary nocardiosis, suggesting a trend towards simultaneous detection of chronic pulmonary infections. Steroid and immunosuppressive drug use was observed in five cases, and β-D-glucan elevation was observed in three of five definite cases of pulmonary infections due to E. dermatitidis. The possibility of E. dermatitidis infection should be considered when Rhodotorula spp. are isolated from cultures of airway-derived specimens, and, in addition to CPA and NTM, identification of E. dermatitidis may be important in chronic pulmonary infections.</p>","PeriodicalId":18797,"journal":{"name":"Mycoses","volume":"67 10","pages":"e13804"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Risk Factors of Tinea Capitis Among Primary School Children in the Grand Lomé Region (Togo), 2021: A Cross-Sectional and Case-Control Study Approach.","authors":"Ameyo M Dorkenoo, Akovi K Adjetey-Toglozombio, Smaila Alidou, Justin Santrao Etassoli, Efoe Sossou, Fiali Lack, Massan J Afankoutché, Emmanuel Awaté, Yaovi Améyapoh","doi":"10.1111/myc.13808","DOIUrl":"https://doi.org/10.1111/myc.13808","url":null,"abstract":"<p><strong>Background: </strong>Tinea capitis is an infectious dermatosis frequent in children, causative fungi variable over time and space. The risk factors associated with this disease are still poorly understood. The objective of this study was to estimate the prevalence of tinea capitis among schoolchildren in Lomé (Togo), identify the fungal species involved and assess the associated risk factors.</p><p><strong>Patients and methods: </strong>It was a cross-sectional and case-control study conducted in primary schools in Lomé from November 2020 to April 2021. All pupils presenting tinea capitis suspected lesions have been sampled, and the scraping and hair were examined by direct microscopy in KOH solution and cultured in Sabouraud dextrose agar with chloramphenicol and cycloheximide. Positive children were matched by age and sex with those without symptoms for case-control study.</p><p><strong>Results: </strong>Out of the 15,087 pupils enrolled, 465 had positive cultures for dermatophytes, corresponding to the tinea capitis prevalence of 3.08% (95% CI [2.59-3.57]). Trichophyton mentagrophytes (81.86%) and Trichophyton soudanense (13.12%) were the majors isolated dermatophytes. The risk factors were mostly living in households with domestic animals, showering less than twice a day, having a history of ringworm, having similar lesions in the same household and sharing personal hygiene items.</p><p><strong>Conclusion: </strong>This study highlights the low prevalence of tinea capitis in schoolchildren in Lomé (Togo), the causative species dominated by T. mentagrophytes and emphasises the importance of environmental and behavioural factors in the mycosis transmission. Implementing preventive measures addressing the identified factors could help to reduce the prevalence of this disease.</p>","PeriodicalId":18797,"journal":{"name":"Mycoses","volume":"67 10","pages":"e13808"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Accuracy of Dermatoscopy Versus Microbiological Culture and Polymerase Chain Reaction in the Diagnosis of Onychomycosis: A Cross‐Sectional Study","authors":"David Navarro‐Pérez, Aroa Tardáguila‐García, Sara García‐Oreja, Diego León‐Herce, Francisco Javier Álvaro‐Afonso, José Luis Lázaro‐Martínez","doi":"10.1111/myc.13799","DOIUrl":"https://doi.org/10.1111/myc.13799","url":null,"abstract":"BackgroundSeveral clinical signs in dermatoscopy are very characteristic of onychomycosis and can be a quick complement for the diagnosis of onychomycosis.ObjectivesThe aim of this study was to evaluate the diagnostic accuracy of dermatoscopy compared to microbiological culture and polymerase chain reaction (PCR), as well as the clinical signs associated with onychomycosis.MethodsThe clinical signs of 125 patients were assessed cross‐sectionally using dermatoscopy, and a positive or negative result was assigned. A sample was then taken for PCR and microbiological culture.ResultsOf the 125 patients, 69.6% (87/125) had positive results when both laboratory tests were combined. When they were not combined, the prevalence was lower at 48% (60/125) with PCR and at 43.2% (54/125) with culture. Furthermore, 76.8% (96/125) were classified as positive with dermatoscopy with a sensitivity of 1, a specificity of 0.76, positive predictive value of 0.91 and negative predictive value of 1 (with 95% confidence intervals). Of the 96 dermatoscopy‐positive samples, 36 were negative with PCR (<jats:italic>p &lt;</jats:italic> 0.001), 42 were negative with culture (<jats:italic>p &lt;</jats:italic> 0.001) and nine were negative when both tests were combined (<jats:italic>p &lt;</jats:italic> 0.001). Clinical signs that were significantly associated with the presence of onychomycosis were subungual hyperkeratosis (dermatoscopy: <jats:italic>p =</jats:italic> 0.004, odds ratio (OR) = 2.438; PCR + microbiological culture: <jats:italic>p =</jats:italic> 0.004, OR = 3.221), subungual detritus (<jats:italic>p =</jats:italic> 0.033, OR = 3.01, only with dermatoscopy) and dermatophytoma (dermatoscopy: <jats:italic>p =</jats:italic> 0.049, OR = 3.02; PCR + microbiological culture: <jats:italic>p =</jats:italic> 0.022, OR = 2.40).ConclusionsThe results suggest that dermatoscopy is a good tool for the diagnosis of onychomycosis but should be used as a complementary test or for screening patients to be sampled for laboratory testing. The combination of the three tests can lead to a reduction of false‐positive and false‐negative clinical and laboratory results. This allows for early diagnosis and specific treatment based on test results.","PeriodicalId":18797,"journal":{"name":"Mycoses","volume":"153 1","pages":"e13799"},"PeriodicalIF":4.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Sources of Resistance to Terbinafine Revealed and Squalene Epoxidase Modelled in the Dermatophyte Fungus Trichophyton interdigitale From Australia.","authors":"Phemelo Mechidi, Jessica Holien, Danilla Grando, Tien Huynh, Ann C Lawrie","doi":"10.1111/myc.13795","DOIUrl":"https://doi.org/10.1111/myc.13795","url":null,"abstract":"<p><strong>Background: </strong>Terbinafine is widely used to treat onychomycosis caused by dermatophyte fungi. Terbinafine resistance in recent years is causing concern. Resistance has so far been associated with single-nucleotide substitutions in the DNA sequence of the enzyme squalene epoxidase (SQLE) but how this affects SQLE functionality is not understood.</p><p><strong>Objectives: </strong>The aim of this study was to understand newly discovered resistance in two Australian strains of Trichophyton interdigitale.</p><p><strong>Patients/methods: </strong>Resistance to terbinafine was tested in four newly isolated strains. Three-dimensional SQLE models were prepared to investigate how the structure of their SQLE affected the binding of terbinafine.</p><p><strong>Results: </strong>This study found the first Australian occurrences of terbinafine resistance in two T. interdigitale strains. Both strains had novel deletion mutations in erg1 and frameshifts during translation. Three-dimensional models had smaller SQLE proteins and open reading frames as well as fewer C-terminal α-helices than susceptible strains. In susceptible strains, the lipophilic tail of terbinafine was predicted to dock stably into a hydrophobic pocket in SQLE lined by over 20 hydrophobic amino acids. In resistant strains, molecular dynamics simulations showed that terbinafine docking was unstable and so terbinafine did not block squalene metabolism and ultimately ergosterol production. The resistant reference strain ATCC MYA-4438 T. rubrum showed a single erg1 mutation that resulted in frameshift during translation, leading to C-terminal helix deletion.</p><p><strong>Conclusions: </strong>Modelling their effects on their SQLE proteins will aid in the design of potential new treatments for these novel resistant strains, which pose clinical problems in treating dermatophyte infections with terbinafine.</p>","PeriodicalId":18797,"journal":{"name":"Mycoses","volume":"67 9","pages":"e13795"},"PeriodicalIF":4.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding Global Access to Topical Onychomycosis Therapy: A Systematic Review and Meta-Analysis.","authors":"S M Nasereddin, J L Li, O S Malallah, G R McClelland, D Morgan, S Meadowcroft, A Bolhuis, S A Jones","doi":"10.1111/myc.13797","DOIUrl":"10.1111/myc.13797","url":null,"abstract":"<p><strong>Introduction: </strong>Equal access to medicines is crucial to ensuring public health, but access is difficult to measure, especially for infections where changes in infective species make treatment choices highly dynamic. This study investigated if the combination of infection prevalence with medicine efficacy and regulatory availability could access medicines access of topical onychomycosis medicines.</p><p><strong>Methods: </strong>Two databases, PubMed and Web of Science, were used to identify relevant information published between 1990 and 2019. For the meta-analysis, human onychomycosis investigations using PCR analysis were included. Reviewers independently selected eligible articles, extracted data and assessed the study quality. A random-effects meta-analysis model with a Freeman-Tukey transformation was employed to the PCR data. For the meta-analysis, the global infection trends and regional differences in the infective organisms were determined.</p><p><strong>Results: </strong>Of the 26 studies analysed, the PCR analysis in 18 studies confirmed onychomycosis in about half of the visually suspected cases (55%, CI 43%-67%). Across all 26 studies dermatophytes were the most prevalent infective organism (57%, CI 37%-76%), but a sub-group analysis showed yeasts predominated in females (31%, CI 0%-84%) (p < 0.0001), in fingernail infections (42%, CI 21%-65%) (p < 0.0001) and in arid countries (p < 0.0001). Combining these results with medicine efficacy data showed that residents from 83 of the 92 countries assessed (90%) could not access the most efficacious topical product, and 22% could not access any broad-spectrum agents. Countries in Africa had the poorest access to topical onychomycosis medicines.</p><p><strong>Conclusion: </strong>This study identified that access to effective topical products for onychomycosis is a global problem. This issue appeared to be due to under-representation of candida infections in pivotal clinical studies of topical onychomycosis products. A head-to-head multicentre study for topical efinaconazole or a novel broad spectrum topical agent is needed to help resolve these access problems.</p><p><strong>Protocol registration: </strong>PROSPERO-CRD42023464744.</p>","PeriodicalId":18797,"journal":{"name":"Mycoses","volume":"67 9","pages":"e13797"},"PeriodicalIF":4.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}