Publications by authors named "Andrew M Borman"

71 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

New weapons to fight a new enemy: A systematic review of drug combinations against the drug-resistant fungus Candida auris.

Mycoses 2021 Mar 27. Epub 2021 Mar 27.

Department of Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Candida auris is an emerging and drug-resistant pathogen. Drug combination is a promising approach against such pathogens. This study was conducted to provide an overview of all the studied drug combinations against C. auris. Relevant articles reporting results of any drug/non-drug combinations against C. auris were found by a systematic search in PubMed, Scopus and Web of Science (ISI), and in Google Scholar up to 1 October 2020. From 187 articles retrieved in the primary search, 23 met the inclusion criteria. In total, 124 different combinations including antifungal with antifungal (45), antifungal with other antimicrobials (11), antifungal with non-antimicrobials (32), antifungal with natural compounds (25) and between natural compounds (11) have been reported. Complete or partial synergistic effects have been reported for 3 out of 45 (6.67%) combinations of two antifungal agents, 8 out of 11 (72.73%) combinations involving antifungal agents and antimicrobials, 15 out of 32 (46.88%) of combinations between antifungal agents with non-antimicrobials, 16 out of 25 (64%) of combinations involving antifungal agents and natural compounds, and 3 out of 11 (22.27%) of combinations involving multiple natural compounds. Antagonistic interactions have been reported for 1 out of 32 (3.13%) and 8 out of 25 (32%) of combinations between antifungal drugs with non-antimicrobials and with natural compounds, respectively. Different drugs/compounds could potentiate the activity of antifungal drugs using this approach. However, despite the availability of this promising initial data, many more studies will be required to elucidate whether favourable interactions observed in vitro might translate into tangible clinical benefits.
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http://dx.doi.org/10.1111/myc.13277DOI 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

The Antifungal Protein 2 (NFAP2): A New Potential Weapon against Multidrug-Resistant Biofilms.

Int J Mol Sci 2021 Jan 14;22(2). Epub 2021 Jan 14.

Institute of Plant Biology, Biological Research Centre, Temesvári krt. 62, 6726 Szeged, Hungary.

is a potential multidrug-resistant pathogen able to persist on indwelling devices as a biofilm, which serve as a source of catheter-associated infections. antifungal protein 2 (NFAP2) is a cysteine-rich, cationic protein with potent anti- activity. We studied the in vitro activity of NFAP2 alone and in combination with fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin against biofilms. The nature of interactions was assessed utilizing the fractional inhibitory concentration index (FICI), a Bliss independence model, and LIVE/DEAD viability assay. NFAP2 exerted synergy with all tested antifungals with FICIs ranging between 0.312-0.5, 0.155-0.5, 0.037-0.375, 0.064-0.375, and 0.064-0.375 for fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin, respectively. These results were confirmed using a Bliss model, where NFAP2 produced 17.54 μM%, 2.16 μM%, 33.31 μM%, 10.72 μM%, and 111.19 μM% cumulative synergy log volume in combination with fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin, respectively. In addition, biofilms exposed to echinocandins (32 mg/L) showed significant cell death in the presence of NFAP2 (128 mg/L). Our study shows that NFAP2 displays strong potential as a novel antifungal compound in alternative therapies to combat biofilms.
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http://dx.doi.org/10.3390/ijms22020771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828714PMC
January 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

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

Relative Frequency of Paradoxical Growth and Trailing Effect with Caspofungin, Micafungin, Anidulafungin, and the Novel Echinocandin Rezafungin against Species.

J Fungi (Basel) 2020 Aug 17;6(3). Epub 2020 Aug 17.

Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.

Rezafungin is a next-generation echinocandin that has favorable pharmacokinetic properties. We compared the occurrence of paradoxical growth (PG) and trailing effect (TE) characteristics to echinocadins with rezafungin, caspofungin, micafungin and anidulafungin using 365 clinical isolates belonging to 13 species. MICs were determined by BMD method according to CLSI (M27 Ed4). Disconnected growth (PG plus TE) was most frequent with caspofungin (49.6%), followed by anidulafungin (33.7%), micafungin (25.7%), while it was least frequent with rezafungin (16.9%). PG was relatively common in the case of caspofungin (30.1%) but was rare in the case of rezafungin (3.0%). , , and exhibited PG most frequently with caspofungin, micafungin or anidulafungin. PG never occurred in the case of isolates. Against and , echinocandins frequently showed PG after 24 h followed by TE after 48 h. All four echinocandins exhibited TE for the majority of and isolates. Disconnected growth was common among species and was echinocandin- and species-dependent. In contrast to earlier echinocandins, PG was infrequently found with rezafungin.
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http://dx.doi.org/10.3390/jof6030136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560028PMC
August 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

Distribution, antifungal susceptibility pattern and intra-Candida albicans species complex prevalence of Candida africana: A systematic review and meta-analysis.

PLoS One 2020 20;15(8):e0237046. Epub 2020 Aug 20.

Department of Medical Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Candida africana is a pathogenic species within the Candida albicans species complex. Due to the limited knowledge concerning its prevalence and antifungal susceptibility profiles, a comprehensive study is overdue. Accordingly, we performed a search of the electronic databases for literature published in the English language between 1 January 2001 and 21 March 2020. Citations were screened, relevant articles were identified, and data were extracted to determine overall intra-C. albicans complex prevalence, geographical distribution, and antifungal susceptibility profiles for C. africana. From a total of 366 articles, 41 were eligible for inclusion in this study. Our results showed that C. africana has a worldwide distribution. The pooled intra-C. albicans complex prevalence of C. africana was 1.67% (95% CI 0.98-2.49). Prevalence data were available for 11 countries from 4 continents. Iran (3.02%, 95%CI 1.51-4.92) and Honduras (3.03%, 95% CI 0.83-10.39) had the highest values and Malaysia (0%) had the lowest prevalence. Vaginal specimens were the most common source of C. africana (92.81%; 155 out of 167 isolates with available data). However, this species has also been isolated from cases of balanitis, from patients with oral lesions, and from respiratory, urine, and cutaneous samples. Data concerning the susceptibility of C. africana to 16 antifungal drugs were available in the literature. Generally, the minimum inhibitory concentrations of antifungal drugs against this species were low. In conclusion, C. africana demonstrates geographical variation in prevalence and high susceptibility to antifungal drugs. However, due to the relative scarcity of existing data concerning this species, further studies will be required to establish more firm conclusions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237046PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440629PMC
October 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

and Effect of Exogenous Farnesol Exposure Against .

Front Microbiol 2020 20;11:957. Epub 2020 May 20.

Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

The spreading of multidrug-resistant is considered as an emerging global health threat. The number of effective therapeutic regimens is strongly limited; therefore, development of novel strategies is needed. Farnesol is a quorum-sensing molecule with a potential antifungal and/or adjuvant effect; it may be a promising candidate in alternative treatment against species including . To examine the effect of farnesol on , we performed experiments focusing on growth, biofilm production ability, production of enzymes related to oxidative stress, triazole susceptibility and virulence. Concentrations ranging from 100 to 300 μM farnesol caused a significant growth inhibition against planktonic cells for 24 h ( < 0.01-0.05). Farnesol treatment showed a concentration dependent inhibition in terms of biofilm forming ability of ; however, it did not inhibit significantly the biofilm development at 24 h. Nevertheless, the metabolic activity of adhered farnesol pre-exposed cells (75 μM) was significantly diminished at 24 h depending on farnesol treatment during biofilm formation ( < 0.001-0.05). Moreover, 300 μM farnesol exerted a marked decrease in metabolic activity against one-day-old biofilms between 2 and 24 h ( < 0.001). Farnesol increased the production of reactive species remarkably, as revealed by 2',7'-dichlorofluorescein (DCF) assay {3.96 ± 0.89 [nmol DCF (OD)] and 23.54 ± 4.51 [nmol DCF (OD)] for untreated cells and farnesol exposed cells, respectively; < 0.001}. This was in line with increased superoxide dismutase level {85.69 ± 5.42 [munit (mg protein)] and 170.11 ± 17.37 [munit (mg protein)] for untreated cells and farnesol exposed cells, respectively; < 0.001}, but the catalase level remained statistically comparable between treated and untreated cells ( > 0.05). Concerning virulence-related enzymes, exposure to 75 μM farnesol did not influence phospholipase or aspartic proteinase activity ( > 0.05). The interaction between fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole and farnesol showed clear synergism (FICI ranges from 0.038 to 0.375) against one-day-old biofilms. Regarding experiments, daily 75 μM farnesol treatment decreased the fungal burden in an immunocompromised murine model of disseminated candidiasis, especially in case of inocula pre-exposed to farnesol ( < 0.01). In summary, farnesol shows a promising therapeutic or adjuvant potential in traditional or alternative therapies such as catheter lock therapy.
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http://dx.doi.org/10.3389/fmicb.2020.00957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251031PMC
May 2020

Comparison of pathogenicity of four clades in a neutropenic bloodstream infection murine model.

Emerg Microbes Infect 2020 Dec;9(1):1160-1169

Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

is an emerging worldwide concern, but comparative data about the virulence of different lineages in mammalian hosts is lacking. Different isolates of the four prevalent clades (South Asian = 5, East Asian = 4, South African = 5, and South American = 5) were compared to assess their virulence in a neutropenic murine bloodstream infection model with as reference. , regardless of clade, proved to be less virulent than Highest overall mortality at day 21 was observed for the South American clade (96%), followed by the South Asian (80%), South African (45%) and East Asian (44%) clades. Fungal burden results showed close correlation with lethality. Histopathological examination revealed large aggregates of blastoconidia and budding yeast cells in the hearts, kidneys and livers but not in the spleens. The myocardium of apparently healthy sacrificed mice as well as of mice found moribund showed contraction band necrosis in case of all lineages. Regardless of clade, the heart and kidneys were the most heavily affected organs. Isolates of the same clade showed differences in virulence in mice, but a markedly higher virulence of the South American clade was clearly demonstrated.
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http://dx.doi.org/10.1080/22221751.2020.1771218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448943PMC
December 2020

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

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

Human Blastomycosis in South Africa Caused by and sp. nov., 1967 to 2014.

J Clin Microbiol 2020 02 24;58(3). Epub 2020 Feb 24.

National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa.

We reevaluated 20 cases of blastomycosis diagnosed in South Africa between 1967 and 2014, with considered to be the etiological agent, in light of newly described species and the use of more advanced technologies. In addition to histopathological and/or culture-based methods, all 20 isolates were phenotypically and genotypically characterized, including multilocus typing of five genes and whole-genome sequencing. Antifungal susceptibility testing was performed as outlined by Clinical and Laboratory Standards Institute documents M27-A3 and M38-A2. We merged laboratory and corresponding clinical case data, where available. Morphological characteristics and phylogenetic analyses of five-gene and whole-genome sequences revealed two groups, both of which were closely related to but distinct from , , and The first group ( = 12) corresponded to the recently described species , and the other ( = 8) is described here as sp. nov. Both species exhibited incomplete conversion to the yeast phase at 37°C and were heterothallic for mating types. All eight isolates belonged to the α mating type. Whole-genome sequencing confirmed distinct species identities as well as the absence of a full orthologue of the gene. Extrapulmonary (skin or bone) disease, probably resulting from hematogenous spread from a primary lung infection, was more common than pulmonary disease alone. Voriconazole, posaconazole, itraconazole, amphotericin B, and micafungin had the most potent activity. Over the 5 decades, South African cases of blastomycosis were caused by species that are distinct from Increasing clinical awareness and access to simple rapid diagnostics may improve the diagnosis of blastomycosis in resource-limited countries.
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http://dx.doi.org/10.1128/JCM.01661-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041581PMC
February 2020

Candida auris outbreak: Mortality, interventions and cost of sustaining control.

J Infect 2019 12 23;79(6):601-611. Epub 2019 Sep 23.

UK National Mycology Reference Laboratory, Public Health England South West Laboratory, Science Quarter, Southmead Hospital, BS10 5NB, UK. Electronic address:

Objective: Candida auris has recently emerged as a global cause of multidrug resistant fungal outbreaks. An outbreak occurred at a tertiary care center in London in 2016. Transmission characteristics, interventions, patient outcomes and cost of resources are described.

Methods: Outbreak interventions included patient isolation, contact screening, single-use equipment, environmental screening and decontamination, staff education, and enhanced surveillance. Risk factors for infection were recorded. Survival probabilities of patients with C. auris and other Candida bloodstream infections (BSI) were calculated. Antifungal susceptibility and epidemiological typing were performed. Actual and opportunity costs of interventions were determined.

Results: 34 patients acquired the organism including 8 with BSI. Clinical infection was significantly associated with prolonged hospital stay, haemodialysis and antifungal therapy. Variable susceptibility to amphotericin and the triazoles was seen and isolates clustered with the South Asian strains. No significant difference was detected in the survival probabilities of C. auris BSI compared to other candidemias. Outbreak control cost in excess of £1 million and £58,000/month during the subsequent year.

Conclusion: C. auris outbreaks can be controlled by a concerted infection control strategy but can be expensive. Transmission maybe prolonged due to patient movements and unidentified transmission mechanisms.
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http://dx.doi.org/10.1016/j.jinf.2019.09.007DOI Listing
December 2019

In vitro activity of rezafungin against common and rare Candida species and Saccharomyces cerevisiae.

J Antimicrob Chemother 2019 12;74(12):3505-3510

Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Background: Rezafungin is a novel echinocandin with excellent activity against common Candida species; however, limited data are available regarding rare Candida species.

Methods: We determined the in vitro susceptibility of 689 clinical isolates of 5 common and 19 rare Candida species, as well as Saccharomyces cerevisiae. The activity of rezafungin was compared with that of anidulafungin, caspofungin, micafungin, amphotericin B and fluconazole, using CLSI broth microdilution methodology (Fourth Edition: M27).

Results: Rezafungin MIC90 values were 0.06 mg/L for Candida albicans (n=125), Candida tropicalis (n=51), Candida dubliniensis (n=22), Candida inconspicua (n=41), Candida sojae (n=10), Candida lipolytica (n=10) and Candida pulcherrima (n=10), 0.12 mg/L for Candida glabrata (n=81), Candida krusei (n=53), Candida kefyr (n=52) and Candida fabianii (n=15), 0.25 mg/L for Candida lusitaniae (n=46) and Candida auris (n=19), 0.5 mg/L for Candida metapsilosis (n=15) and S. cerevisiae (n=21), 1 mg/L for Candida orthopsilosis (n=15) and Candida guilliermondii (n=27) and 2 mg/L for Candida parapsilosis sensu stricto (n=59). Caspofungin MIC90 values were 0.25-2 mg/L for all species, while micafungin and anidulafungin MIC90 values were similar to those of rezafungin. Fluconazole resistance was found in C. albicans (5.6%) and C. glabrata (4.9%); rezafungin was effective against these isolates as well. Amphotericin B MIC values did not exceed 2 mg/L.

Conclusions: Rezafungin showed excellent in vitro activity against both WT and azole-resistant Candida species, as well as against S. cerevisiae. Rezafungin had similar activity to other echinocandins (excluding caspofungin) against common Candida species and, notably, against clinically relevant uncommon Candida species.
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http://dx.doi.org/10.1093/jac/dkz390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857195PMC
December 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

Farnesol increases the activity of echinocandins against Candida auris biofilms.

Med Mycol 2020 Apr;58(3):404-407

Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Nagyerdei krt. 98., Hungary.

Candida auris biofilms exhibit decreased susceptibility to echinocandins, which is associated with poorer clinical outcomes. Farnesol is a quorum-sensing molecule enhancing the activity of antifungals; therefore, we evaluated the in vitro effect of farnesol with anidulafungin, caspofungin, or micafungin against biofilms using fractional inhibitory concentration indexes (FICI), Bliss independence model, LIVE/DEAD-assay and scanning electron microscopy. Based on mathematical models, farnesol caused synergism in eleven out of twelve cases (FICIs range 0.133-0.507; Bliss synergy volume range 70.39-204.6 μM2%). This was confirmed by microscope images of combination-exposed biofilms. Our study showed the prominent effect of farnesol with echinocandins against C. auris biofilms.
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http://dx.doi.org/10.1093/mmy/myz057DOI Listing
April 2020

Resistance to echinocandin antifungal agents in the United Kingdom in clinical isolates of Candida glabrata: Fifteen years of interpretation and assessment.

Med Mycol 2020 Feb;58(2):219-226

Centre for Research in Bioscience, University of the West of England, Coldharbour Lane, Bristol, UK.

Candidemia is widely reported as the fourth most common form of bloodstream infection worldwide. Reports of breakthrough cases of candidemia are increasing, especially in the context of a move away from azole antifungals as prophylactic or first line treatment toward the use of echinocandin agents. The global evaluation of echinocandin antifungal susceptibility since 2003 has included switches in testing methodologies and the move to a sentinel echinocandin approach for classification reporting. This study compiles previously unpublished data from echinocandin susceptibility testing of UK clinical isolates of C. glabrata received at the Public Health England Mycology Reference Laboratory from 2003 to 2016 and reevaluates the prevalence of resistance in light of currently accepted testing protocols. From 2015 onward, FKS gene mutation detection using a novel Pyrosequencing® assay was assessed as a predictor of echinocandin resistance alongside conventional susceptibility testing. Overall, our data show that echinocandin resistance in UK isolates of C. glabrata is a rare phenomenon and prevalence has not appreciably increased in the last 14 years. The pyrosequencing assay was able to successfully detect hot spot mutations in FKS1 and FKS2, although not all isolates that exhibited phenotypic resistance demonstrated detectable hot spot mutations. We propose that a rapid genomic based detection method for FKS mutations, as part of a multifactorial approach to susceptibility testing, could help provide accurate and timely management decisions especially in regions where echinocandin resistance has been reported to be emerging in this important pathogen.
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http://dx.doi.org/10.1093/mmy/myz053DOI Listing
February 2020

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

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

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