Publications by authors named "Elizabeth M Johnson"

99 Publications

Erratum for Borman and Johnson, "Name Changes for Fungi of Medical Importance, 2018 to 2019".

J Clin Microbiol 2021 Mar 19;59(4). Epub 2021 Mar 19.

UK National Mycology Reference Laboratory, National Infection Service, Public Health England South-West, Bristol, United Kingdom.

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http://dx.doi.org/10.1128/JCM.00331-21DOI Listing
March 2021

Genomic epidemiology of a case cluster in Glasgow, Scotland, 2018.

Microb Genom 2021 Mar 23;7(3). Epub 2021 Feb 23.

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

In 2018, a cluster of two cases of cryptococcosis occurred at the Queen Elizabeth University Hospital (QEUH) in Glasgow, Scotland (UK). It was postulated that these cases may have been linked to pigeon droppings found on the hospital site, given there have been previous reports of associated with pigeon guano. Although some samples of pigeon guano taken from the site yielded culturable yeast from genera related to , they have since been classified as or spp., and no isolates of were recovered from either the guano or subsequent widespread air sampling. In an attempt to further elucidate any possible shared source of the clinical isolates, we used whole-genome sequencing and phylogenetic analysis to examine the relationship of the two isolates from the QEUH cases, along with two isolates from sporadic cases treated at a different Glasgow hospital earlier in 2018. Our work demonstrated that these four clinical isolates were not clonally related; while all isolates were from the VNI global lineage and of the same mating type (MATα), the genotypes of the two QEUH isolates were separated by 1885 base changes and belonged to different sub-lineages, recently described as the intercontinental sub-clades VNIa-93 and VNIa-5. In contrast, one of the two sporadic 2018 clinical isolates was determined to belong to the VNIb sub-lineage and the other classified as a VNIV/VNI hybrid. Our work demonstrated that the two 2018 QEUH isolates and the two prior clinical isolates were all genetically distinct. It was not possible to determine whether the QEUH genotypes stemmed from independent sources or from the same source, i.e. pigeons carrying different genotypes, but it should be noted that whilst members of allied genera within the were isolated from the hospital environment, there were no environmental isolations of .
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http://dx.doi.org/10.1099/mgen.0.000537DOI Listing
March 2021

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

Mycoses 2021 Apr 24;64(4):394-404. Epub 2020 Dec 24.

Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital (CWZ), Nijmegen, The Netherlands.

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.
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http://dx.doi.org/10.1111/myc.13227DOI Listing
April 2021

Biosensors and Diagnostics for Fungal Detection.

J Fungi (Basel) 2020 Dec 8;6(4). Epub 2020 Dec 8.

Medical Research Council Centre for Medical Mycology, The University of Exeter University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter EX4 4QD, UK.

Early detection is critical to the successful treatment of life-threatening infections caused by fungal pathogens, as late diagnosis of systemic infection almost always equates with a poor prognosis. The field of fungal diagnostics has some tests that are relatively simple, rapid to perform and are potentially suitable at the point of care. However, there are also more complex high-technology methodologies that offer new opportunities regarding the scale and precision of fungal diagnosis, but may be more limited in their portability and affordability. Future developments in this field are increasingly incorporating new technologies provided by the use of new format biosensors. This overview provides a critical review of current fungal diagnostics and the development of new biophysical technologies that are being applied for selective new sensitive fungal biosensors to augment traditional diagnostic methodologies.
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http://dx.doi.org/10.3390/jof6040349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770582PMC
December 2020

Reply to Kidd et al., "New Names for Fungi of Medical Importance: Can We Have Our Cake and Eat It Too?"

J Clin Microbiol 2021 Feb 18;59(3). Epub 2021 Feb 18.

UK National Mycology Reference Laboratory, Public Health England South-West, Bristol, United Kingdom.

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http://dx.doi.org/10.1128/JCM.02896-20DOI Listing
February 2021

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

J Clin Microbiol 2020 12 17;59(1). Epub 2020 Dec 17.

UK National Mycology Reference Laboratory, Public Health England South-West, Bristol, United Kingdom.

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 from COVID-19 patients (including three that exhibited environmental triazole resistance). Diagnostic tests performed included 1,000 (1-3)-β-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, -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.
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http://dx.doi.org/10.1128/JCM.02136-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771443PMC
December 2020

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

J Clin Microbiol 2021 Jan 21;59(2). Epub 2021 Jan 21.

UK National Mycology Reference Laboratory, National Infection Service, Public Health England South-West, Bristol, United Kingdom.

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.
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http://dx.doi.org/10.1128/JCM.01811-20DOI Listing
January 2021

Blastomycosis: The Great Pretender.

J Thorac Imaging 2020 Sep 25. Epub 2020 Sep 25.

Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI.

Blastomycosis is an endemic fungal infection caused by Blastomyces, a soil-dwelling dimorphic fungus found predominantly in North America. In this pictorial essay, we illustrate the varied imaging features of blastomycosis along with a brief description of the epidemiology, clinical aspects, and differential diagnosis, emphasizing clues that can help radiologists arrive at this diagnosis.
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http://dx.doi.org/10.1097/RTI.0000000000000562DOI Listing
September 2020

causing a subcutaneous palmar cyst in an otherwise healthy UK resident.

Med Mycol Case Rep 2020 Sep 5;29:43-45. Epub 2020 Aug 5.

UK National Mycology Reference Laboratory, Public Health England, Science Quarter, Southmead Hospital, Bristol, BS10 5NB, United Kingdom.

is a ubiquitous genus encompassing more than forty species, a number of which have been associated with superficial or systemic infections in humans, and other hot- or cold-blooded animals. Here we report a human case of subcutaneous mycotic cyst caused by . To our knowledge, this is only the third reported human infection caused by , all three of which involved subcutaneous nodules in patients who had resided in the United Kingdom.
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http://dx.doi.org/10.1016/j.mmcr.2020.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424171PMC
September 2020

Talaromycosis in a renal transplant recipient returning from South China.

Transpl Infect Dis 2021 Feb 31;23(1):e13447. Epub 2020 Aug 31.

Department of Renal and Pancreas Transplantation, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Oxford Road, Manchester, UK.

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.
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http://dx.doi.org/10.1111/tid.13447DOI Listing
February 2021

Candida auris in the UK: Introduction, dissemination, and control.

PLoS Pathog 2020 07 30;16(7):e1008563. Epub 2020 Jul 30.

UK National Mycology Reference Laboratory, National Infections Service, Public Health England, Science Quarter, Southmead Hospital, Bristol, United Kingdom and MRC Centre for Medical Mycology, University of Exeter, United Kingdom.

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http://dx.doi.org/10.1371/journal.ppat.1008563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392211PMC
July 2020

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

Med Mycol 2021 Mar;59(3):253-258

UK National Mycology Reference Laboratory, National Infection Service, Public Health England South-West, Bristol, United Kingdom.

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.
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http://dx.doi.org/10.1093/mmy/myaa049DOI Listing
March 2021

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

Med Mycol 2020 Oct;58(7):996-999

UK National Mycology Reference Laboratory, Public Health England South-West, Bristol, United Kingdom.

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.
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http://dx.doi.org/10.1093/mmy/myaa022DOI Listing
October 2020

Colonic Basidiobolomycosis-An Unusual Presentation of Eosinophilic Intestinal Inflammation.

Front Pediatr 2020 21;8:142. Epub 2020 Apr 21.

Great Ormond Street Hospital for Children, London, United Kingdom.

Basidiobolomycosis is a rare fungal disease caused by . Involvement of the gastrointestinal tract is unusual and poses both a diagnostic and therapeutic challenge, as clinical signs are non-specific and predisposing risk factors are lacking. It can mimick inflammatory bowel disease, primary immunodeficiency, or a malignancy and should be considered in patients who do not respond to standard therapy. We present the case of a 22 months old boy with confirmed colonic Basidiobolomycosis, who presented with severe eosinophilic inflammation of the gastrointestinal tract. Panfungal PCR performed on DNA extracted directly from a tissue sample confirmed the presence of . He made a full recovery with a combination of surgery and prolonged targeted antifungal medication.
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http://dx.doi.org/10.3389/fped.2020.00142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186448PMC
April 2020

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.

J Antimicrob Chemother 2020 05;75(5):1194-1205

PHE UK National Mycology Reference Laboratory, Science Quarter, Southmead Hospital, Bristol, UK.

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.
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http://dx.doi.org/10.1093/jac/dkz568DOI Listing
May 2020

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

Med Mycol 2020 Aug;58(6):744-755

Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.

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.
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http://dx.doi.org/10.1093/mmy/myz127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398771PMC
August 2020

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

J Digit Imaging 2020 06;33(3):735-746

Department of Radiology & Imaging Sciences, Emory University, 1364 Clifton Rd NE D107, Atlanta, GA, 30322, USA.

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.
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http://dx.doi.org/10.1007/s10278-019-00311-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256153PMC
June 2020

Cardiac Magnetic Resonance for the Evaluation of Suspected Cardiac Thrombus: Conventional and Emerging Techniques.

J Vis Exp 2019 06 11(148). Epub 2019 Jun 11.

Department of Diagnostic Imaging, H. Lee Moffitt Cancer Center and Research Institute;

We present the conventional cardiac magnetic resonance (CMR) protocol for evaluating a suspected thrombus and highlight emerging techniques. The appearance of a mass on certain magnetic resonance (MR) sequences can help differentiate a thrombus from competing diagnoses such as a tumor. T1 and T2 signal characteristics of a thrombus are related to the evolution of hemoglobin properties. A thrombus typically does not enhance following contrast administration, which also helps differentiation from a tumor. We also highlight the emerging role of T1 mapping in the evaluation of a thrombus, which can add another level of support in diagnosis. Prior to any CMR exam, patient screening and interviews are critical to ensure safety and to optimize patient comfort. Effective communication during the exam between the technologist and the patient promotes proper breath holding technique and higher quality images. Volumetric post processing and structured reporting are helpful to ensure that the radiologist answers the ordering services' question and communicates these results effectively. Optimal pre-MR safety evaluation, CMR exam execution, and post exam processing and reporting allow for delivery of high quality radiological service in the evaluation of a suspected cardiac thrombus.
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http://dx.doi.org/10.3791/58808DOI Listing
June 2019

National mycology laboratory diagnostic capacity for invasive fungal diseases in 2017: Evidence of sub-optimal practice.

J Infect 2019 08 21;79(2):167-173. Epub 2019 Jun 21.

Healthcare Associated Infection & Antimicrobial Resistance Division, National Infection Service, Public Health England, 61 Colindale Avenue, London, UK.

A survey of laboratory testing capabilities for systemic fungal pathogens was undertaken in the UK, to identify where improved compliance with published standards and guidelines is required and to inform antifungal stewardship (AFS). The survey captured information from laboratories in the UK on diagnostic capacity for invasive fungal diseases (IFD), including identification, serology, molecular diagnostics and susceptibility testing. The survey was circulated in March 2017 through key networks. Of 154 laboratories providing diagnostic mycology services in the UK, 80 (52%) responded to the survey. Results indicated that 85% of respondents identified fungal isolates from high risk patients to species level, and that many laboratories (78%) could access local susceptibility testing for yeasts, whereas 17% could for Aspergillus species. However, direct microscopy was only used in 49% as a first line investigation on samples where it would be appropriate. A low number of respondents identified yeasts cultured from intravascular line tips to species level (63%) and even fewer fully identified urine isolates from critically ill patients (42%) or the immunocompromised (39%). Less than half of respondents advised therapeutic drug monitoring (TDM) for flucytosine. Few laboratories had access to local β-glucan (4%) or galactomannan (20%) testing. The survey highlights that the current level of fungal diagnostics in the UK is below accepted best practice with an urgent need to improve across many diagnostic areas including the timely accessibility of fungal biomarkers, susceptibility testing and provision of TDM testing. Improvements are important to facilitate the delivery of diagnostic driven AFS strategies as well as appropriate management of IFD.
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http://dx.doi.org/10.1016/j.jinf.2019.06.009DOI Listing
August 2019

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

Antimicrob Agents Chemother 2019 08 25;63(8). Epub 2019 Jul 25.

PHE UK National Mycology Reference Laboratory, Science Quarter, Southmead Hospital, Bristol, 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 infections. Established susceptibility profiles and clinical interpretive breakpoints are available for fluconazole with , , , and , 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 clade (, , and ). 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 ). 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.
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http://dx.doi.org/10.1128/AAC.00211-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658760PMC
August 2019

A Review of Innovative Teaching Methods.

Acad Radiol 2019 01 9;26(1):101-113. Epub 2018 May 9.

Department of Radiology, University of Washington, 4245 Roosevelt Way NE, Seattle, WA 98105. Electronic address:

Teaching is one of the important roles of an academic radiologist. Therefore, it is important that radiologists are taught how to effectively educate and, in turn, to act as role models of these skills to trainees. This is reinforced by the Liaison Committee on Medical Education which has the requirement that all residents who interact with and teach medical students must undergo training in effective methods of teaching. Radiologists are likely familiar with the traditional didactic lecture-type teaching format. However, there are many newer innovative teaching methods that could be added to the radiologist's teaching repertoire, which could be used to enhance the traditional lecture format. The Association of University Radiologists Radiology Research Alliance Task Force on Noninterpretive Skills therefore presents a review of several innovative teaching methods, which include the use of audience response technology, long-distance teaching, the flipped classroom, and active learning.
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http://dx.doi.org/10.1016/j.acra.2018.03.025DOI Listing
January 2019

A black mould death: A case of fatal cerebral phaeohyphomycosis caused by .

Med Mycol Case Rep 2019 Jun 28;24:23-26. Epub 2019 Feb 28.

Department of Neurology, Charing Cross Hospital, Imperial College NHS Trust, London W6 8RF, UK.

Cladophialophora bantiana is a neurotropic mould and primary cause of cerebral phaeohyphomycoses, which presents with brain abscesses in both immunocompromised and immunocompetent individuals. It is associated with high mortality due to delay in diagnosis and absence of standardised therapy. We present a case of fatal cerebral phaeohyphomycosis in a 67-year-old Caucasian man. Diagnosis was achieved by histopathological examination of brain tissue followed by conventional culture and molecular identification. We highlight diagnostic and treatment challenges involved.
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http://dx.doi.org/10.1016/j.mmcr.2019.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403067PMC
June 2019

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

J Clin Microbiol 2019 05 26;57(5). Epub 2019 Apr 26.

UK National Mycology Reference Laboratory (MRL), Public Health England South-West, Bristol, United Kingdom.

is a serious nosocomial health risk, with widespread outbreaks occurring in hospitals worldwide. Sequence analyses of outbreak isolates revealed that has simultaneously emerged as four distinct continentally restricted clonal lineages. We previously reported multiple independent introductions of 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 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 , 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 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.
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http://dx.doi.org/10.1128/JCM.02055-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498034PMC
May 2019

Practical Presentation Pearls: Evidence-based Recommendations From the Psychology and Physiology Literature.

Acad Radiol 2019 01 9;26(1):93-100. Epub 2018 Aug 9.

Department of Radiology, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania.

Oral presentations remain a common teaching method in academic radiology. The goal of these presentations is to transfer knowledge from the presenter's brain to brains in the audience in a way that sticks. A number of studies from the recent psychological and physiological literature offer some rather practical and evidence-based advice on ways to optimize our oral presentations. The purpose of this paper is to summarize this work, and to give examples of how it can be harnessed to increase the efficacy of radiology presentations, whether they are for resident education, a continuing medical education course, or for a scientific presentation at a national radiology meeting.
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http://dx.doi.org/10.1016/j.acra.2018.04.008DOI Listing
January 2019

Rapid and robust identification of clinical isolates of Talaromyces marneffei based on MALDI-TOF mass spectrometry or dimorphism in Galleria mellonella.

Med Mycol 2019 Nov;57(8):969-975

UK National Mycology Reference Laboratory (MRL), Public Health England South-West, Bristol, United Kingdom.

Talaromyces marneffei is a thermally dimorphic fungal pathogen that causes serious infections particularly in patients with human immunodeficiency virus (HIV). Although the mould form typically produces a characteristic red-diffusing pigment, and conidia from penicillate heads, several nonpathogenic Talaromyces/Penicillium species are morphologically and phenotypically similar. While those other species do not exhibit thermal dimorphism, conversion of T. marneffei to the distinctive fission yeast form in vitro is arduous and frequently incomplete. Here we show that T. marneffei can be rapidly and unambiguously discriminated from related nonpathogenic Talaromyces/Penicillium spp., either by matrix-assisted laser desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry or conversion to fission yeast after introduction into Galleria mellonella. Conversion of T. marneffei conidia to the fission yeast form in G. mellonella larvae occurred as early as 24 h post inoculation at 37oC. Identification by MALDI-TOF was possible after supplementation of the commercial Bruker database with in-house mass spectral profiles created from either the yeast or mycelial phase of T. marneffei. In addition, we show that in-house generated mass spectral profiles could be successfully used to identify T. marneffei with a recently published on-line MALDI-TOF database, circumventing the need to create extensive in-house additional databases for rarely encountered fungal pathogens.
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http://dx.doi.org/10.1093/mmy/myy162DOI Listing
November 2019

mPGES-1-Mediated Production of PGE and EP4 Receptor Sensing Regulate T Cell Colonic Inflammation.

Front Immunol 2018 14;9:2954. Epub 2018 Dec 14.

Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States.

PGE is a lipid mediator of the initiation and resolution phases of inflammation, as well as a regulator of immune system responses to inflammatory events. PGE is produced and sensed by T cells, and autocrine or paracrine PGE can affect T cell phenotype and function. In this study, we use a T cell-dependent model of colitis to evaluate the role of PGE on pathological outcome and T-cell phenotypes. CD4 T effector cells either deficient in mPGES-1 or the PGE receptor EP4 are less colitogenic. Absence of T cell autocrine mPGES1-dependent PGE reduces colitogenicity in association with an increase in CD4RORγt cells in the lamina propria. In contrast, recipient mice deficient in mPGES-1 exhibit more severe colitis that corresponds with a reduced capacity to generate FoxP3 T cells, especially in mesenteric lymph nodes. Thus, our research defines how mPGES-1-driven production of PGE by different cell types in distinct intestinal locations impacts T cell function during colitis. We conclude that PGE has profound effects on T cell phenotype that are dependent on the microenvironment.
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http://dx.doi.org/10.3389/fimmu.2018.02954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302013PMC
October 2019

Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis.

Nat Commun 2018 12 11;9(1):5288. Epub 2018 Dec 11.

Medical Research Council Centre for Medical Mycology at the University of Aberdeen, Aberdeen, AB25 2ZD, UK.

The high global burden of over one million annual lethal fungal infections reflects a lack of protective vaccines, late diagnosis and inadequate chemotherapy. Here, we have generated a unique set of fully human anti-Candida monoclonal antibodies (mAbs) with diagnostic and therapeutic potential by expressing recombinant antibodies from genes cloned from the B cells of patients suffering from candidiasis. Single class switched memory B cells isolated from donors serum-positive for anti-Candida IgG were differentiated in vitro and screened against recombinant Candida albicans Hyr1 cell wall protein and whole fungal cell wall preparations. Antibody genes from Candida-reactive B cell cultures were cloned and expressed in Expi293F human embryonic kidney cells to generate a panel of human recombinant anti-Candida mAbs that demonstrate morphology-specific, high avidity binding to the cell wall. The species-specific and pan-Candida mAbs generated through this technology display favourable properties for diagnostics, strong opsono-phagocytic activity of macrophages in vitro, and protection in a murine model of disseminated candidiasis.
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http://dx.doi.org/10.1038/s41467-018-07738-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290022PMC
December 2018

The burden of serious fungal disease in the UK - infections with "rare" organisms.

J Infect 2018 12 31;77(6):561-571. Epub 2018 Oct 31.

PHE UK National Mycology Reference Laboratory, Science Quarter, Southmead Hospital, Bristol, United Kingdom.

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http://dx.doi.org/10.1016/j.jinf.2018.10.010DOI Listing
December 2018

A novel dermatophyte relative, Nannizzia perplicata sp. nov., isolated from a case of tinea corporis in the United Kingdom.

Med Mycol 2018 Oct 16. Epub 2018 Oct 16.

Public Health England UK National Mycology Reference Laboratory, Bristol.

A novel dermatophyte was isolated from skin scales of a female patient presenting with tinea corporis of the wrist and arm. Her principal risk factor was long-term corticosteroid use for underlying Lupus autoimmune syndrome. Microscopic examination of skin scales from lesions revealed hyphae consistent with dermatophyte infection, and a morphologically identical fungus grew in pure culture on all cultures of skin scales. Repeat isolation of the same organism from persistent lesions five months later confirmed the novel species as the causative agent. Microscopic examination revealed predominantly smooth, thin-walled macroconidia, with large numbers of unicellular aleuriospores of varied shapes and sizes. Since the isolate exhibited considerable microscopic pleomorphism, sharing morphological features consistent with several dermatophyte genera, it was subjected to multi-locus phylogenetic analyses employing a total of six different loci. Sequence analyses of all loci revealed that the isolate clustered with species within Nannizzia but diverged from all known members of the genus by 2 to 13% depending on locus analyzed. The isolate exhibited high minimum inhibitory concentrations for terbinafine in vitro, which might explain why the infection had failed to respond to two cycles of oral treatment with this antifungal agent. Interestingly, sequences in GenBank of an unnamed "Microsporum sp" isolated from leg skin of a patient in the Czech Republic showed greater than 99% identity across all of the loci analysed in common, indicating that this novel organism, which we describe here as Nannizzia perplicata sp. nov., is likely not restricted to the UK.
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http://dx.doi.org/10.1093/mmy/myy099DOI Listing
October 2018

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

N Engl J Med 2018 10;379(14):1322-1331

From Oxford University Hospitals NHS Foundation Trust (D.W.E., H.M., I.M., R.M., L.B., M.M., R.N., M.S., T.C., T.E.A.P., D.W.C., K.J.M.J.) and Nuffield Department of Medicine (D.W.E., A.E.S., T.P.Q., D.G., S.G., D.F., A.S.W., T.E.A.P., D.W.C.), Big Data Institute (D.W.E.), and the National Institute for Health Research Health Protection Unit in Healthcare Associated Infections and Antimicrobial Resistance (D.W.E., A.E.S., T.P.Q., A.S.W., T.E.A.P., D.W.C.), University of Oxford, Oxford, Public Health England, National Infection Service, Colindale, London (P.H., C.S.B., D.W.C.), the National Mycology Reference Laboratory, Public Health England, Bristol (A.M.B., E.M.J.), and Public Health England, Porton Down, Salisbury (G.M.) - all in the United Kingdom.

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.).
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http://dx.doi.org/10.1056/NEJMoa1714373DOI Listing
October 2018