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Background: Invasive fungal infections (IFIs) present significant challenges, especially among immunocompromised patients, with associated high morbidity, mortality and significant economic impact. Diagnostic difficulties and the emergence of antifungal resistance necessitates enhanced antifungal stewardship (AFS) efforts. Methods: We report outcomes from a review of our multidisciplinary approach to AFS, based in a 1300-bed teaching hospital in the South-West of England. Retrospectively reviewing all adult and paediatric cases over 12 months in 2022, we investigated demographics, diagnosis, antifungal therapy and adherence to AFS advice, including clinical, mycological, financial and teamwork metrics. Data were extracted from our AFS database, supported by pharmacy records. Results: The AFS multidisciplinary team (MDT) reviewed 111 patients, with 30 day and 1 year mortality of 22.7% and 35.4%, respectively. IFIs classified as proven accounted for 26%, with fungal pathogens identified in 36.3% of cases. Antifungal consumption (by 25.1%) and expenditure (by 59.9%) decreased from 2018 to 2022. The AFS MDT issued 324 recommendations, with a 93% acceptance rate. Conclusions: Our approach to AFS, centred around a weekly MDT, demonstrated improvements in IFI management, antifungal consumption and cost-efficiency. This single-centre study highlights the value of a comprehensive, collaborative approach to AFS involving experts in mycology, infection, radiology, antifungal therapies and clinical teams. The programme's success in paediatric and adult populations and the near-universal acceptance of its recommendations show its potential as a model for replication. It represents a model for enhancing patient care and AFS practices, with future directions aimed at expanding service reach and the integration of further rapid diagnostic modalities.
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OBJECTIVE: To evaluate the frequency and content of media coverage pertaining to artificial intelligence (AI) and radiology in the United States from 1998 to 2023. METHODS: The ProQuest US Newsstream database was queried for print and online articles mentioning AI and radiology published between January 1, 1998, and March 30, 2023. A Boolean search using terms related to radiology and AI was used to retrieve full text and publication information. One of 9 readers with radiology expertise independently reviewed randomly assigned articles using a standardized scoring system. RESULTS: 379 articles met inclusion criteria, of which 290 were unique and 89 were syndicated articles. Most had a positive sentiment (74 %) towards AI, while negative sentiment was far less common (9 %). Frequency of positive sentiment was highest in articles with a focus on AI and radiology (86 %) and lowest in articles focusing on AI and non-medical topics (55 %). The net impact of AI on radiology was most commonly presented as positive (60 %). Benefits of AI were more frequently mentioned (76 %) than potential harms (46 %). Radiologists were interviewed or quoted in less than one-third of all articles. CONCLUSION: Portrayal of the impact of AI on radiology in US media coverage was mostly positive, and advantages of AI were more frequently discussed than potential risks. However, articles with a general non-medical focus were more likely to have a negative sentiment regarding the impact of AI on radiology than articles with a more specific focus on medicine and radiology. Radiologists were infrequently interviewed or quoted in media coverage.
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Human fungal infections are a historically neglected area of disease research, yet they cause more than 1.5 million deaths every year. Our understanding of the pathophysiology of these infections has increased considerably over the past decade, through major insights into both the host and pathogen factors that contribute to the phenotype and severity of these diseases. Recent studies are revealing multiple mechanisms by which fungi modify and manipulate the host, escape immune surveillance and generate complex comorbidities. Although the emergence of fungal strains that are less susceptible to antifungal drugs or that rapidly evolve drug resistance is posing new threats, greater understanding of immune mechanisms and host susceptibility factors is beginning to offer novel immunotherapeutic options for the future. In this Review, we provide a broad and comprehensive overview of the pathobiology of human fungal infections, focusing specifically on pathogens that can cause invasive life-threatening infections, highlighting recent discoveries from the pathogen, host and clinical perspectives. We conclude by discussing key future challenges including antifungal drug resistance, the emergence of new pathogens and new developments in modern medicine that are promoting susceptibility to infection.
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The emergent fungal pathogen Candida auris is increasingly recognised as an important cause of healthcare-associated infections globally. It is highly transmissible, adaptable, and persistent, resulting in an organism with significant outbreak potential that risks devastating consequences. Progress in the ability to identify C. auris in clinical specimens is encouraging, but laboratory diagnostic capacity and surveillance systems are lacking in many countries. Intrinsic resistance to commonly used antifungals, combined with the ability to rapidly acquire resistance to therapy, substantially restricts treatment options and novel agents are desperately needed. Despite this, outbreaks can be interrupted, and mortality avoided or minimised, through the application of rigorous infection prevention and control measures with an increasing evidence base. This review provides an update on epidemiology, the impact of the COVID-19 pandemic, risk factors, identification and typing, resistance profiles, treatment, detection of colonisation, and infection prevention and control measures for C. auris. This review has informed a planned 2024 update to the United Kingdom Health Security Agency (UKHSA) guidance on the laboratory investigation, management, and infection prevention and control of Candida auris. A multidisciplinary response is needed to control C. auris transmission in a healthcare setting and should emphasise outbreak preparedness and response, rapid contact tracing and isolation or cohorting of patients and staff, strict hand hygiene and other infection prevention and control measures, dedicated or single-use equipment, appropriate disinfection, and effective communication concerning patient transfers and discharge.
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Antifúngicos , COVID-19 , Candida auris , Candidiasis , Control de Infecciones , Humanos , Candidiasis/prevención & control , Candidiasis/epidemiología , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Control de Infecciones/métodos , Candida auris/efectos de los fármacos , COVID-19/prevención & control , COVID-19/epidemiología , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Inglaterra/epidemiología , Infección Hospitalaria/prevención & control , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , SARS-CoV-2 , Farmacorresistencia Fúngica , Candida/efectos de los fármacos , Candida/clasificación , Candida/aislamiento & purificación , Brotes de Enfermedades/prevención & controlAsunto(s)
Antifúngicos , Farmacorresistencia Fúngica , Terbinafina , Tiña , Trichophyton , Humanos , Terbinafina/uso terapéutico , Antifúngicos/uso terapéutico , Tiña/tratamiento farmacológico , Tiña/microbiología , Tiña/diagnóstico , Trichophyton/aislamiento & purificación , Trichophyton/efectos de los fármacos , Masculino , Londres , Viaje , Persona de Mediana Edad , FemeninoRESUMEN
OBJECTIVE: To report the identification and results of susceptibility testing for fungal isolates from the cornea or contact lens care systems. MATERIALS AND METHODS: In this retrospective epidemiological study, we searched the results of fungal cultures from cornea or contact lens systems referred for identification and susceptibility testing to the United Kingdom National Mycology Reference Laboratory between October 2016 and March 2022. For each fungal isolate, we recorded the genus and species of the fungus and the minimum inhibitory concentration (MIC) to six antifungal agents available to treat corneal infection (amphotericin, econazole, itraconazole, natamycin, posaconazole, and voriconazole). RESULTS: There were 600 isolates from 585 patients, comprising 374 (62%) from corneal samples and 226 from contact lenses and care systems, of which 414 (69%) isolates were moulds (filamentous fungi) and 186 (31%) were yeasts. The most frequent moulds isolated were Fusarium spp (234 isolates, 39%) and Aspergillus spp (62, 10%). The most frequent yeasts isolated were Candida spp (112, 19%), predominantly Candida parapsilosis (65, 11%) and Candida albicans (33, 6%), with 35 isolates (6%) of Meyerozyma guilliermondii. In vitro susceptibility was greatest for natamycin (347 moulds tested, mode 4 mg/L, range 0.25-64 mg/L; 98 yeasts tested, mode 4 mg/L, range 0.5-32 mg/L), with susceptibility for 94% for moulds and 99% yeasts. Of the 16 isolates interpreted as highly resistant to natamycin (MIC ≥16 mg/L), 13 were Aspergillus flavus complex. CONCLUSIONS: In vitro susceptibility supports the use of natamycin for the empiric treatment of fungal keratitis in the UK.
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Antifúngicos , Natamicina , Humanos , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Natamicina/farmacología , Estudios Retrospectivos , Voriconazol , Hongos , Córnea , Aspergillus , Pruebas de Sensibilidad MicrobianaRESUMEN
Numerous fungal species of medical importance have been recently subjected to and will likely continue to undergo nomenclatural changes as a result of the application of molecular approaches to fungal classification together with abandonment of dual nomenclature. Here, we summarize those changes affecting key groups of fungi of medical importance, explaining the mycological (taxonomic) rationale that underpinned the changes and the clinical relevance/importance (where such exists) of the key nomenclatural revisions. Potential mechanisms to mitigate unnecessary taxonomic instability are suggested, together with approaches to raise awareness of important changes to minimize potential clinical confusion.
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Candida auris is a multi-drug resistant human fungal pathogen that has become a global threat to human health due to its drug resistant phenotype, persistence in the hospital environment and propensity for patient to patient spread. Isolates display variable aggregation that may affect the relative virulence of strains. Therefore, dissection of this phenotype has gained substantial interest in recent years. We studied eight clinical isolates from four different clades (I-IV); four of which had a strongly aggregating phenotype and four of which did not. Genome analysis identified polymorphisms associated with loss of cell surface proteins were enriched in weakly-aggregating strains. Additionally, we identified down-regulation of chitin synthase genes involved in the synthesis of the chitinous septum. Characterisation of the cells revealed no ultrastructural defects in cytokinesis or cell separation in aggregating isolates. Strongly and weakly aggregating strains did not differ in net surface charge or in cell surface hydrophobicity. The capacity for aggregation and for adhesion to polystyrene microspheres were also not correlated. However, aggregation and extracellular matrix formation were all increased at higher growth temperatures, and treatment with the amyloid protein inhibitor Thioflavin-T markedly attenuated aggregation. Genome analysis further indicated strain specific differences in the genome content of GPI-anchored proteins including those encoding genes with the potential to form amyloid proteins. Collectively our data suggests that aggregation is a complex strain and temperature dependent phenomenon that may be linked in part to the ability to form extracellular matrix and cell surface amyloids.
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Using a citizen science approach, we identify a country-wide exposure to aerosolized spores of a human fungal pathogen, Aspergillus fumigatus, that has acquired resistance to the agricultural fungicide tebuconazole and first-line azole clinical antifungal drugs. Genomic analysis shows no distinction between resistant genotypes found in the environment and in patients, indicating that at least 40% of azole-resistant A. fumigatus infections are acquired from environmental exposures. Hotspots and coldspots of aerosolized azole-resistant spores were not stable between seasonal sampling periods. This suggests a high degree of atmospheric mixing resulting in an estimated per capita cumulative annual exposure of 21 days (±2.6). Because of the ubiquity of this measured exposure, it is imperative that we determine sources of azole-resistant A. fumigatus to reduce treatment failure in patients with aspergillosis.
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Aspergilosis , Ciencia Ciudadana , Humanos , Aspergillus fumigatus/genética , Farmacorresistencia Fúngica/genética , Aspergilosis/tratamiento farmacológico , Aspergilosis/microbiología , Antifúngicos/farmacología , Azoles/farmacologíaRESUMEN
BACKGROUND. Newspapers are an important source of information for the public about low-dose CT (LDCT) lung cancer screening (LCS) and may influence public perception and knowledge of this important cancer screening service. OBJECTIVE. The purpose of this article was to evaluate the volume, content, and other characteristics of articles pertaining to LCS that have been published in U.S. newspapers. METHODS. The ProQuest U.S. Newsstream database was searched for U.S. newspaper articles referring to LCS published between January 1, 2010 (the year of publication of the National Lung Screening Trial results), and March 28, 2022. Search terms included "lung cancer screening(s)," "lung screening(s)," "low dose screening(s)," and "LDCT." Search results were reviewed to identify those articles mentioning LCS. Characteristics of included articles and originating newspapers were extracted. Articles were divided among nine readers, who independently assessed article sentiment regarding LCS and additional article content using a standardized form. RESULTS. The final analysis included 859 articles, comprising 816 nonsyndicated articles published in a single newspaper and 43 syndicated articles published in multiple newspapers. Sentiment regarding LCS was positive in 76% (651/859) of articles, neutral in 21% (184/859), and negative in 3% (24/859). Frequency of positive sentiment was lowest (61%) for articles published from 2010 to 2012; frequency of negative sentiment was highest (8%) for articles published in newspapers in the highest quartile for weekly circulation. LCS enrollment criteria were mentioned in 52% of articles, smoking cessation programs in 28%, need for annual CT in 27%, and shared decision-making in 4%. Cost or insurance coverage for LCS was mentioned in 33% in articles. A total of 64% of articles mentioned at least one benefit of LCS (most commonly early detection or possible cure of lung cancer), and 23% mentioned at least one harm (most commonly false-positives). A total of 9% of articles interviewed or mentioned a radiologist. CONCLUSION. The sentiment of U.S. newspaper articles covering LCS from 2010 to 2022 was overall positive. However, certain key elements of LCS were infrequently mentioned. CLINICAL IMPACT. The findings highlight areas for potential improvement of LCS media coverage; radiologists have an opportunity to take a more active role in this coverage.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Detección Precoz del CáncerRESUMEN
The current article summarizes recent changes in nomenclature for fungi of medical importance published in the years 2020 to 2021, including new species and revised names for existing ones. Many of the revised names have been widely adopted without further discussion. However, those that concern common pathogens of humans may take longer to achieve general usage, with new and current names reported together to engender increasing familiarity with the correct taxonomic classification.
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Hongos , Hongos/clasificaciónRESUMEN
Objective: To describe the clinical and radiographic findings in a large cohort of patients with positive cultures for Nocardia emphasizing the differences between invasive disease and colonization. Patients and Methods: We conducted a single-center, retrospective cohort study of 133 patients with a positive Nocardia isolate between August 1, 1998, and November 30, 2018, and a computed tomography (CT) of the chest within 30 days before or after the bacteria isolation date. Results: Patients with colonization were older (71 vs 65 years; P=.004), frequently with chronic obstructive pulmonary disease (56.8% vs 16.9%; P<.001) and coronary artery disease (47.7% vs 27%, P=.021), and had Nocardia isolated exclusively from lung specimens (100% vs 83.1%; P=.003). On CT of the chest, they had frequent airway disease (84.1% vs 51.7%; P<.001). Patients with invasive nocardiosis had significantly (P<.05) more diabetes, chronic kidney disease, solid organ transplant, use of corticosteroids, antirejection drugs, and prophylactic sulfa. They had more fever (25.8% vs 2.3%; P<.001), cutaneous lesions (14.6% vs 0%; P=.005), fatigue (18% vs 0%; P=.001), pulmonary nodules (52.8% vs 27.3%; P=.006), and free-flowing pleural fluid (63.6% vs 29.4%; P=.024). The patterns of nodule distribution were different-diffuse for invasive nocardiosis and peribronchiolar for Nocardia colonization. Conclusion: The isolation of Nocardia in sputum from a patient with respiratory symptoms does not equal active infection. Only by combining clinical and chest CT findings, one could better differentiate between invasive nocardiosis and Nocardia colonization.
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Fusarium is a polyphyletic genus of plant pathogens, members of which can cause opportunistic human infections with varying superficial and systemic presentations, including disseminated infections which typically occur in immunocompromised patients and have a poor prognosis. Treatment is challenging due to intrinsic resistance to many antifungal agents, and antifungal susceptibility testing is therefore essential. Early suspicion, isolation of the organism, and prompt initiation of management are crucial to improving survival. We present a case of disseminated Bisifusarium infection following toxic epidermal necrolysis in a child with B-cell acute lymphoblastic leukemia, successfully treated with liposomal amphotericin B, voriconazole, flucytosine, and terbinafine.
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Fusariosis , Fusarium , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Síndrome de Stevens-Johnson , Humanos , Niño , Fusariosis/diagnóstico , Fusariosis/tratamiento farmacológico , Fusariosis/etiología , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/tratamiento farmacológico , Síndrome de Stevens-Johnson/etiología , Antifúngicos/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Huésped InmunocomprometidoRESUMEN
The gold standard for diagnosis of invasive fungal infections caused by filamentous fungi remains the visualization of fungal elements in fluids, and biopsy/tissue collected from a normally sterile body site. Parallel recovery of viable fungus from the sample subsequently permits antifungal susceptibility testing of the individual isolate. Central to both processes is the appropriate processing of tissue specimens to avoid damaging fungal elements and optimize viable organism recovery. Historically, mycologists have proposed that homogenization (grinding or bead-beating) of tissue should be avoided in cases of suspected fungal infection as it likely damages hyphae, instead preferring to chop tissue into small portions (dicing) for direct microscopic examination and culture. Here, we have compared the two processes directly on material from clinical patient cases of mucoromycosis and invasive aspergillosis. Representative portions of fresh biopsy samples were processed in parallel either by chopping (dicing) in the mycology reference laboratory or by bead-beating in the adjoining general microbiology laboratory. Aliquots of the samples were then cultured under identical conditions and subjected to direct microscopic examination. The results demonstrated that tissue homogenization significantly reduced (i) organism recovery rates in cases of both mucoromycosis and invasive aspergillosis and (ii) the number of fungal elements detectable upon direct microscopic examination. To our knowledge, this is the first study to directly compare these alternative processing methods and despite only employing a limited number of samples the data presented here, provide support for the perceived mycological wisdom that homogenization of tissue samples should be avoided when filamentous fungal infections are suspected.
The gold standard for diagnosis of fungal infections remains the visualization of fungal elements in samples from usually sterile sites. Here we show that certain methods employed for processing biopsy samples significantly impact the ability to detect and grow fungi from genuine cases of infection.
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Microscopía , Micología , Animales , Microscopía/veterinariaRESUMEN
Susceptibility testing of isolates of Candida auris is helpful as a guide to the selection of the most appropriate antifungal agent for treatment as different clades and strains within clades often demonstrate markedly different susceptibility profiles. Some strains are relatively susceptible to all antifungal drugs, but most demonstrate innate resistance to fluconazole, many are cross-resistant to other azoles and others demonstrate resistance to other classes of antifungal. The finding of multi-drug resistance, where an isolate is resistant to two or more classes of antifungal agent, is not uncommon, and development of resistance during a course of treatment has also been documented. This chapter describes a reference broth microdilution method for susceptibility testing and a commercially available gradient strip method.
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Antifúngicos , Candida , Antifúngicos/farmacología , Candida auris , Fluconazol/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
Subcutaneous fungal infections, which typically result from traumatic introduction (implantation) of fungal elements into the skin or underlying tissues, can present as a range of different clinical entities including phaeohyphomycosis, chromoblastomycosis, subcutaneous nodules or masses, and genuine eumycetoma. Here, we mined our laboratory information management system for such infections in humans and domestic animals for the period 2016-2022, including (i) fungal isolates referred for identification and/or susceptibility testing; (ii) infections diagnosed at our laboratory using panfungal PCR approaches on infected tissue; and (iii) organisms cultured in our laboratory from biopsies. In total, 106 cases were retrieved, involving 39 fungal species comprising 26 distinct genera. Subcutaneous infections with Alternaria species were the most frequent (36 cases), which possibly reflects the ubiquitous nature of this common plant pathogen. A substantial proportion of Alternaria spp. isolates exhibited reduced in vitro susceptibility to voriconazole. Notably, a significant number of subcutaneous infections were diagnosed in renal and other solid organ transplant recipients post transplantation, suggesting that humans may harbour "inert" subcutaneous fungal elements from historical minor injuries that present as clinical infections upon later immunosuppression. The current study underscores the diversity of fungi that can cause subcutaneous infections. While most organisms catalogued here were responsible for occasional infections, several genera (Alternaria, Exophiala, Phaeoacremonuim, Scedosporium) were more frequently recovered in our searches, suggesting that they possess virulence factors that facilitate subcutaneous infections and/or inhabit natural niches that make them more likely to be traumatically inoculated.
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Infections caused by the fungal pathogen Aspergillus fumigatus are increasingly resistant to first-line azole antifungal drugs. However, despite its clinical importance, little is known about how susceptible patients acquire infection from drug-resistant genotypes in the environment. Here, we present a population genomic analysis of 218 A. fumigatus isolates from across the UK and Ireland (comprising 153 clinical isolates from 143 patients and 65 environmental isolates). First, phylogenomic analysis shows strong genetic structuring into two clades (A and B) with little interclade recombination and the majority of environmental azole resistance found within clade A. Second, we show occurrences where azole-resistant isolates of near-identical genotypes were obtained from both environmental and clinical sources, indicating with high confidence the infection of patients with resistant isolates transmitted from the environment. Third, genome-wide scans identified selective sweeps across multiple regions indicating a polygenic basis to the trait in some genetic backgrounds. These signatures of positive selection are seen for loci containing the canonical genes encoding fungicide resistance in the ergosterol biosynthetic pathway, while other regions under selection have no defined function. Lastly, pan-genome analysis identified genes linked to azole resistance and previously unknown resistance mechanisms. Understanding the environmental drivers and genetic basis of evolving fungal drug resistance needs urgent attention, especially in light of increasing numbers of patients with severe viral respiratory tract infections who are susceptible to opportunistic fungal superinfections.
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Antiinfecciosos , Aspergillus fumigatus , Aspergillus fumigatus/genética , Azoles/farmacología , Farmacorresistencia Fúngica/genética , Humanos , Metagenómica , Pruebas de Sensibilidad MicrobianaRESUMEN
Dyspnea is a common presenting symptom among patients with cardiopulmonary diseases. However, several neuromuscular and chest wall conditions are often overlooked and under-recognized causes of dyspnea. These disorders frequently adversely affect the structure and function of the ventilatory pump (diaphragm, accessory muscles of ventilation) and can precipitate respiratory failure despite normal lung parenchyma. Weakened musculature impairs clearance of airway secretions leading to aspiration and pneumonia, further compromising respiratory function. Radiologists should be aware of the pathophysiology and imaging manifestations of these conditions and might suggest them to be causes of dyspnea which otherwise may not have been considered by referring clinicians.