Changes in fungal taxonomy: mycological rationale and clinical implications.

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.

Name Changes for Fungi of Medical Importance, 2020 to 2021.

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.

U.S. Newspaper Coverage of Lung Cancer Screening From 2010 to 2022.

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.

Disseminated Bisifusarium infection following toxic epidermal necrolysis in a child with B-cell acute lymphoblastic leukemia.

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.

The importance of appropriate processing and direct microscopic examination for the timely diagnosis and management of invasive infections caused by filamentous fungi.

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.

A Candida auris Outbreak and Its Control in an Intensive Care Setting.

BACKGROUND: Candida auris is an emerging and multidrug-resistant pathogen. Here we report the epidemiology of a hospital outbreak of C. auris colonization and infection. METHODS: After identification of a cluster of C. auris infections in the neurosciences intensive care unit (ICU) of the Oxford University Hospitals, United Kingdom, we instituted an intensive patient and environmental screening program and package of interventions. Multivariable logistic regression was used to identify predictors of C. auris colonization and infection. Isolates from patients and from the environment were analyzed by whole-genome sequencing. RESULTS: A total of 70 patients were identified as being colonized or infected with C. auris between February 2, 2015, and August 31, 2017; of these patients, 66 (94%) had been admitted to the neurosciences ICU before diagnosis. Invasive C. auris infections developed in 7 patients. When length of stay in the neurosciences ICU and patient vital signs and laboratory results were controlled for, the predictors of C. auris colonization or infection included the use of reusable skin-surface axillary temperature probes (multivariable odds ratio, 6.80; 95% confidence interval [CI], 2.96 to 15.63; P<0.001) and systemic fluconazole exposure (multivariable odds ratio, 10.34; 95% CI, 1.64 to 65.18; P=0.01). C. auris was rarely detected in the general environment. However, it was detected in isolates from reusable equipment, including multiple axillary skin-surface temperature probes. Despite a bundle of infection-control interventions, the incidence of new cases was reduced only after removal of the temperature probes. All outbreak sequences formed a single genetic cluster within the C. auris South African clade. The sequenced isolates from reusable equipment were genetically related to isolates from the patients. CONCLUSIONS: The transmission of C. auris in this hospital outbreak was found to be linked to reusable axillary temperature probes, indicating that this emerging pathogen can persist in the environment and be transmitted in health care settings. (Funded by the National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University and others.).

Name Changes for Fungi of Medical Importance, 2018 to 2019.

The current article summarizes recent changes in nomenclature for fungi of medical importance published in the years 2018 to 2019, 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.

CHROMagarTM Candida Plus: A novel chromogenic agar that permits the rapid identification of Candida auris.

Candida auris is a serious nosocomial health risk, with widespread outbreaks in hospitals worldwide. Successful management of such outbreaks has depended upon intensive screening of patients to identify those that are colonized and the subsequent isolation or cohorting of affected patients to prevent onward transmission. Here we describe the evaluation of a novel chromogenic agar, CHROMagarTM Candida Plus, for the specific identification of Candida auris isolates from patient samples. Candida auris colonies on CHROMagarTM Candida Plus are pale cream with a distinctive blue halo that diffuses into the surrounding agar. Of over 50 different species of Candida and related genera that were cultured in parallel, only the vanishingly rare species Candida diddensiae gave a similar appearance. Moreover, both the rate of growth and number of colonies of C. auris recovered from swabs of pure and mixed Candida species were substantially increased on CHROMagarTM Candida Plus agar when compared with growth on the traditional mycological isolation medium, Sabouraud dextrose agar. Taken together, the present data suggest that CHROMagarTM Candida Plus agar is an excellent alternative to current conventional mycological media for the screening of patients who are potentially colonized/infected with Candida auris, can be reliably used to identify this emerging fungal pathogen, and should be tested in a clinical setting. LAY ABSTRACT: Candida auris is a novel pathogenic yeast that has been associated with large hospital outbreaks across several continents. Affected patients become colonized, predominantly on the skin, with large quantities of C. auris which they then shed into the hospital environment. Identification of C. auris is challenging using routine laboratory methods, and time consuming when patients are colonized with a mixture of different Candida species. Here we demonstrate that a novel chromogenic agar, CHROMagarTM Candida Plus, permits the rapid differentiation of C. auris from a wide range of other yeast species and is potentially ideally suited to screening of patients that are suspected of being colonized or infected with this medically important yeast.

The considerable impact of the SARS-CoV-2 pandemic and COVID-19 on the UK National Mycology Reference Laboratory activities and workload.

Starting late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating global pandemic of coronavirus-19 disease (COVID-19) with ∼179 million cases and ∼3.9 million deaths to date. COVID-19 ranges from asymptomatic infection to severe illness with acute respiratory distress requiring critical care in up to 40% of hospitalized patients. Numerous reports have identified COVID-19-associated pulmonary aspergillosis (CAPA) as an important infective complication of COVID-19. In the UK, the pandemic has had unprecedented impacts on the National Health Service (NHS'): each wave of infections required hospitals to reconfigure for large surges in patients requiring intensive care, to the detriment of most aspects of non-COVID care including planned operations, outpatient appointments, general practitioner consultations and referrals. The UK National Mycology Reference Laboratory (MRL) offers a comprehensive service for the diagnosis and management of fungal disease nationwide, with a test portfolio that includes: diagnosis of allergies to fungal and other respiratory allergens; diagnosis of superficial and invasive/systemic fungal infections using traditional mycological, serological and molecular approaches; identification and susceptibility testing of the causative fungi; therapeutic drug monitoring of patients receiving antifungal therapy. Here, we describe the impact of the first 14 months of the COVID-19 pandemic on MRL activities. Changes to MRL workload closely mirrored many of the NHS-wide challenges, with marked reductions in 'elective' mycological activities unrelated to the pandemic and dramatic surges in tests that contributed to the diagnosis and management of COVID-19-related secondary fungal infections, in particular CAPA and candidemia in COVID-19 patients in intensive care. LAY SUMMARY: The COVID-19 pandemic has had an unprecedented impact on the UK National Health Service, with hospitals forced to repeatedly reconfigure to prepare for large surges in COVID-19 patients. Here we describe the impact of the first 14 months of the UK pandemic on the workload of the National Mycology Reference Laboratory.

Talaromycosis in a renal transplant recipient returning from South China.

Talaromycosis is a fungal infection endemic in Southeast Asia. We report a case of a renal transplant recipient who developed infection after a trip to South China. She presented with constitutional symptoms and was found to have an FDG-avid lung mass. Histopathology demonstrated small yeast cells and culture grew Talaromyces marneffei. The patient was treated with 2 weeks of liposomal amphotericin B followed by itraconazole. The dose of tacrolimus was significantly reduced because of the interaction with itraconazole. Mycophenolate mofetil was discontinued. After 12 months of treatment, the mass had completely resolved. Talaromycosis has mainly been reported in patients with AIDS and is uncommon among solid organ transplant recipients. The immune response against T. marneffei infection is mediated predominantly by T cells and macrophages. The diagnosis may not be suspected outside of endemic areas. We propose a therapeutic approach in transplant patients by extrapolating the evidence from the HIV literature and following practices applied to other endemic mycoses.

A pseudo-outbreak of Rhinocladiella similis in a bronchoscopy unit of a tertiary care teaching hospital in London, United Kingdom.

Outbreaks of fungal infections due to emerging and rare species are increasingly reported in healthcare settings. We investigated a pseudo-outbreak of Rhinocladiella similis in a bronchoscopy unit of a tertiary care teaching hospital in London, UK. We aimed to determine route of healthcare-associated transmission and prevent additional infections. From July 2018 through February 2019, we detected a pseudo-outbreak of R. similis isolated from bronchoalveolar lavage (BAL) fluid samples collected from nine patients who had undergone bronchoscopy in a multispecialty teaching hospital, during a period of 8 months. Isolates were identified by MALDI-TOF mass spectrometry. Antifungal susceptibility testing was performed by EUCAST broth microdilution. To determine genetic relatedness among R. similis isolates, we undertook amplified fragment length polymorphism analysis. To determine the potential source of contamination, an epidemiological investigation was carried out. We reviewed patient records retrospectively and audited steps taken during bronchoscopy as well as the subsequent cleaning and decontamination procedures. Fungal cultures were performed on samples collected from bronchoscopes and automated endoscope washer-disinfector systems. No patient was found to have an infection due to R. similis either before or after bronchoscopy. One bronchoscope was identified to be used among all affected patients with positive fungal cultures. Physical damage was found in the index bronchoscope; however, no fungus was recovered after sampling of the affected scope or the rinse water of automated endoscope washer-disinfectors. Use of the scope was halted, and, during the following 12-month period, Rhinocladiella species were not isolated from any BAL specimen. All pseudo-outbreak isolates were identified as R. similis with high genetic relatedness (>90% similarity) on ALFP analysis. The study emphasises the emergence of a rare and uncommon black yeast R. similis, with reduced susceptibility to echinocandins, in a bronchoscope-related pseudo-outbreak with a potential water-related reservoir. Our findings highlight the importance of prolonged fungal culture and species-level identification of melanised yeasts isolated from bronchoscopy samples. Possibility of healthcare-associated transmission should be considered when R. similis is involved in clinical microbiology samples.

COVID-19-Associated Invasive Aspergillosis: Data from the UK National Mycology Reference Laboratory.

COVID-19-associated pulmonary aspergillosis (CAPA) was recently reported as a potential infective complication affecting critically ill patients with acute respiratory distress syndrome following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with incidence rates varying from 8 to 33% depending on the study. However, definitive diagnosis of CAPA is challenging. Standardized diagnostic algorithms and definitions are lacking, clinicians are reticent to perform aerosol-generating bronchoalveolar lavages for galactomannan testing and microscopic and cultural examination, and questions surround the diagnostic sensitivity of different serum biomarkers. Between 11 March and 14 July 2020, the UK National Mycology Reference Laboratory received 1,267 serum and respiratory samples from 719 critically ill UK patients with COVID-19 and suspected pulmonary aspergillosis. The laboratory also received 46 isolates of Aspergillus fumigatus from COVID-19 patients (including three that exhibited environmental triazole resistance). Diagnostic tests performed included 1,000 (1-3)-ß-d-glucan and 516 galactomannan tests on serum samples. The results of this extensive testing are presented here. For a subset of 61 patients, respiratory specimens (bronchoalveolar lavage specimens, tracheal aspirates, and sputum samples) in addition to serum samples were submitted and subjected to galactomannan testing, Aspergillus-specific PCR, and microscopy and culture. The incidence of probable/proven and possible CAPA in this subset of patients was approximately 5% and 15%, respectively. Overall, our results highlight the challenges in biomarker-driven diagnosis of CAPA, especially when only limited clinical samples are available for testing, and the importance of a multimodal diagnostic approach involving regular and repeat testing of both serum and respiratory samples.

MIC distributions for amphotericin B, fluconazole, itraconazole, voriconazole, flucytosine and anidulafungin and 35 uncommon pathogenic yeast species from the UK determined using the CLSI broth microdilution method.

BACKGROUND: Epidemiological cut-off values and clinical interpretive breakpoints have been developed for a number of antifungal agents with the most common Candida species that account for the majority of infections due to pathogenic yeasts species. However, less-common species, for which susceptibility data are limited, are increasingly reported in high-risk patients and breakthrough infections. METHODS: The UK National Mycology Reference Laboratory performs routine antifungal susceptibility testing of clinical yeast isolates submitted from across the UK. Between 2002 and 2016, >32 000 isolates representing 94 different yeast species were referred to the laboratory. Here we present antifungal susceptibility profiles generated over this period for amphotericin B, fluconazole, voriconazole, itraconazole, anidulafungin and flucytosine against 35 species of uncommon yeast using CLSI methodologies. MIC data were interpreted against epidemiological cut-off values and clinical breakpoints developed with Candida albicans, in order to identify species with unusually skewed MIC distributions that potentially indicate resistance. RESULTS: Potential resistance to at least one antifungal agent (>10% of isolates with MICs greater than the epidemiological cut-off or clinical breakpoint) was evidenced for 29/35 species examined here. Four species exhibited elevated MICs with all of the triazole antifungal drugs against which they were tested, and 21 species exhibited antifungal resistance to agents from at least two different classes of antifungal agent. CONCLUSIONS: This study highlights a number of yeast species with unusual MIC distributions and provides data to aid clinicians in deciding which antifungal regimens may be appropriate when confronted with infections with rarer yeasts.

Lessons from isavuconazole therapeutic drug monitoring at a United Kingdom Reference Center.

We determined isavuconazole serum concentrations for 150 UK patients receiving standard isavuconazole dosing regimens, including serial therapeutic drug monitoring for several patients on prolonged therapy. Mean trough isavuconazole concentrations in these patients were virtually identical to those reported previously from clinical trials, although greater variability was seen in patients below 18 years of age. Serial monitoring in patients receiving prolonged therapy suggested gradual, near-linear accumulation of the drug over many weeks.

The environmental stress sensitivities of pathogenic Candida species, including Candida auris, and implications for their spread in the hospital setting.

Candida auris is an emerging pathogenic yeast of significant clinical concern because of its frequent intrinsic resistance to fluconazole and often other antifungal drugs and the high mortality rates associated with systemic infections. Furthermore, C. auris has a propensity for persistence and transmission in health care environments. The reasons for this efficient transmission are not well understood, and therefore we tested whether enhanced resistance to environmental stresses might contribute to the ability of C. auris to spread in health care environments. We compared C. auris to other pathogenic Candida species with respect to their resistance to individual stresses and combinations of stresses. Stress resistance was examined using in vitro assays on laboratory media and also on hospital linen. In general, the 17 C. auris isolates examined displayed similar degrees of resistance to oxidative, nitrosative, cationic and cell wall stresses as clinical isolates of C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei, C. guilliermondii, C. lusitaniae and C. kefyr. All of the C. auris isolates examined were more sensitive to low pH (pH 2, but not pH 4) compared to C. albicans, but were more resistant to high pH (pH 13). C. auris was also sensitive to low pH, when tested on contaminated hospital linen. Most C. auris isolates were relatively thermotolerant, displaying significant growth at 47°C. Furthermore, C. auris was relatively resistant to certain combinations of combinatorial stress (e.g., pH 13 plus 47°C). Significantly, C. auris was sensitive to the stress combinations imposed by hospital laundering protocol (pH > 12 plus heat shock at >80°C), suggesting that current laundering procedures are sufficient to limit the transmission of this fungal pathogen via hospital linen.

mPGES1-Dependent Prostaglandin E2 (PGE2) Controls Antigen-Specific Th17 and Th1 Responses by Regulating T Autocrine and Paracrine PGE2 Production.

The integration of inflammatory signals is paramount in controlling the intensity and duration of immune responses. Eicosanoids, particularly PGE2, are critical molecules in the initiation and resolution of inflammation and in the transition from innate to acquired immune responses. Microsomal PGE synthase 1 (mPGES1) is an integral membrane enzyme whose regulated expression controls PGE2 levels and is highly expressed at sites of inflammation. PGE2 is also associated with modulation of autoimmunity through altering the IL-23/IL-17 axis and regulatory T cell (Treg) development. During a type II collagen-CFA immunization response, lack of mPGES1 impaired the numbers of CD4+ regulatory (Treg) and Th17 cells in the draining lymph nodes. Ag-experienced mPGES1-/- CD4+ cells showed impaired IL-17A, IFN-γ, and IL-6 production when rechallenged ex vivo with their cognate Ag compared with their wild-type counterparts. Additionally, production of PGE2 by cocultured APCs synergized with that of Ag-experienced CD4+ T cells, with mPGES1 competence in the APC compartment enhancing CD4+ IL-17A and IFN-γ responses. However, in contrast with CD4+ cells that were Ag primed in vivo, exogenous PGE2 inhibited proliferation and skewed IL-17A to IFN-γ production under Th17 polarization of naive T cells in vitro. We conclude that mPGES1 is necessary in vivo to mount optimal Treg and Th17 responses during an Ag-driven primary immune response. Furthermore, we uncover a coordination of autocrine and paracrine mPGES1-driven PGE2 production that impacts effector T cell IL-17A and IFN-γ responses.

Radiology, Mobile Devices, and Internet of Things (IoT).

Radiology by its nature is intricately connected to the Internet and is at the forefront of technology in medicine. The past few years have seen a dramatic rise in Internet-based technology in healthcare, with imaging as a core application. Numerous Internet-based applications and technologies have made forays into medicine, and for radiology it is more seamless than in other clinical specialties. Many applications in the practice of radiology are Internet based and more applications are being added every day. Introduction of mobile devices and their integration into imaging workflow has reinforced the role played by the Internet in radiology. Due to the rapid proliferation of wearable devices and smartphones, IoT-enabled technology is evolving healthcare from conventional hub-based systems to more personalized healthcare systems. This article briefly discusses how the IoT plays a useful role in daily imaging workflow and current and potential future applications, how mobile devices can be integrated into radiology workflows, and the impact of the IoT on resident and medical student education, research, and patient engagement in radiology.

Candida auris: a Review of the Literature.

The emerging pathogen Candida auris has been associated with nosocomial outbreaks on five continents. Genetic analysis indicates the simultaneous emergence of separate clades of this organism in different geographical locations. Invasive infection and colonization have been detected predominantly in patients in high-dependency settings and have garnered attention due to variable antifungal resistance profiles and transmission within units instituting a range of infection prevention and control measures. Issues with the identification of C. auris using both phenotypic and molecular techniques have raised concerns about detecting the true scale of the problem. This review considers the literature available on C. auris and highlights the key unknowns, which will provide direction for further work in this field.

Fluconazole Resistance in Isolates of Uncommon Pathogenic Yeast Species from the United Kingdom.

The triazole drug fluconazole remains one of the most commonly prescribed antifungal drugs, both for prophylaxis in high-risk patients and also as a second-line treatment option for invasive Candida infections. Established susceptibility profiles and clinical interpretive breakpoints are available for fluconazole with Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, which account for the majority of infections due to pathogenic yeast species. However, less common species for which only limited susceptibility data are available are increasingly reported in high-risk patients and from breakthrough infections. The UK National Mycology Reference Laboratory performs routine antifungal susceptibility testing of clinical isolates of pathogenic yeast submitted from across the United Kingdom. Between 2002 and 2016, ∼32,000 isolates were referred, encompassing 94 different yeast species. Here, we present fluconazole antifungal susceptibility data generated using a CLSI methodology over this 15-year period for 82 species (2,004 isolates) of less common yeast and yeast-like fungi, and amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and anidulafungin, with members of the Nakaseomyces clade (C. glabrata, Candida nivariensis, and Candida bracarensis). At least 22 different teleomorph genera, comprising 45 species, exhibited high MICs when tested with fluconazole (>20% of isolates with MICs higher than the clinical breakpoint [≥8 mg/liter] proposed for C. albicans). Since several of these species have been reported anecdotally from breakthrough infections and therapeutic failures in patients receiving fluconazole, the current study underscores the importance of rapid and accurate yeast identification and may aid clinicians dealing with infections with rarer yeasts to decide whether fluconazole would be appropriate.

Candida auris Isolates of the Southern Asian and South African Lineages Exhibit Different Phenotypic and Antifungal Susceptibility Profiles In Vitro.

Candida auris is a serious nosocomial health risk, with widespread outbreaks occurring in hospitals worldwide. Sequence analyses of outbreak isolates revealed that C. auris has simultaneously emerged as four distinct continentally restricted clonal lineages. We previously reported multiple independent introductions of C. auris isolates from at least three of these lineages (the Southern Asia, South African, and Japanese/Korean lineages) into hospitals across the United Kingdom and that isolates circulating in the United Kingdom displayed two different cell phenotypes which correlated with differences in virulence in Galleria mellonella wax moths. Here, we compared the phenotypic characteristics and antifungal susceptibilities of isolates representative of the three geographic clades circulating in the United Kingdom. Isolates of the South African and Japanese/Korean lineages, but not those of the Southern Asian lineage, grew well on media containing actidione. However, unlike Southern Asian lineage isolates, they were unable to produce even rudimentary pseudohyphae in culture. Importantly, although all isolates were fluconazole resistant in vitro, fluconazole and voriconazole exhibited significantly higher MICs against isolates of the South African lineage than against isolates of the Southern Asian lineage. A similar trend was seen with minimum fungicidal concentrations (MFCs), with higher MFCs of the triazole antifungal agents being seen for the South African lineage isolates. Finally, the formation of large cellular aggregates was seen only with isolates of the South African and Japanese/Korean lineages, which correlates with the reduced virulence observed previously in Galleria wax moths inoculated with such isolates. Intriguingly, aggregation could be reversibly induced in isolates of the Southern Asian lineage by exposure to triazole and echinocandin antifungals but not by exposure to amphotericin B or flucytosine.