Publications by authors named "Jacques F Meis"

359 Publications

In vitro activity of eight antifungal drugs against Chaetomiaceae.

Med Mycol 2021 Nov 13. Epub 2021 Nov 13.

Bioprocess Engineering and Biotechnology Graduate Program; Microbiology, Parasitology and Pathology Post-Graduation Program, Department of Basic Pathology, Federal University of Paraná, Curitiba, Brazil.

The incidence of infections caused by uncommon Chaetomiaceae (Chaetomium and related species) in humans has increased in recent years. The in vitro activity of eight antifungal drugs (amphotericin B, five azoles, two echinocandins) against 42 morphologically identified Chaetomium strains was determined according to the Clinical and Laboratory Standards Institute (CLSI) guideline. The strains were subsequently identified based on sequences of the internal transcribed spacer 1 and 2 including the intervening 5.8S nrDNA region (ITS) and the partial β tubulin gene (tub2). Chaetomium globosum (n = 24), was the most frequently isolated species, followed by Amesia atrobrunnea (syn. Chaetomium atrobrunnea, n = 6), Dichotomopilus dolichotrichus (syn. Chaetomium dolichotrichum, n = 2) and Acrophialophora jodhpurensis, Chaetomium coarctatum, C. elatum, C. gracile, C. subaffine, C. tarraconense, C. unguicola, Dichotomopilus sp., Dichotomopilus variostiolatus, Ovatospora brasiliensis (all represented by a single strain). The geometric mean of the minimum inhibitory concentrations/minimum effective concentrations (MICs/MECs) of the antifungals across all strains were (in increasing order): micafungin 0.12 µg/mL, itraconazole and posaconazole 0.21 µg/mL, amphotericin B 0.25 µg/mL, voriconazole 0.45 µg/mL, isavuconazole 0.54 µg/mL, caspofungin 2.57 µg/mL, and fluconazole 45.25 µg/mL. Micafungin had the lowest geometric mean followed by amphotericin B which had the largest range against tested isolates. All examined C. globosum strains had a similar antifungal susceptibility patterns. Fluconazole and caspofungin could not be considered as an option for treatment of infections caused by Chaetomium and chaetomium-like species.
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http://dx.doi.org/10.1093/mmy/myab074DOI Listing
November 2021

Development of a multiplex PCR short tandem repeat typing scheme for .

J Clin Microbiol 2021 Nov 17:JCM0203221. Epub 2021 Nov 17.

Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, 6532 SZ Nijmegen, The Netherlands.

is a human pathogenic yeast that can cause candidemia with the lowest 90-day survival rate in comparison to other species. Infections occur frequently in immunocompromised patients and several outbreaks in health care facilities have been described. Here, we developed a short tandem repeat (STR) typing scheme for to allow for fast and cost-effective genotyping of an outbreak and compared identified relatedness of ten isolates to SNP calling from whole-genome sequencing (WGS). From a selection of 14 novel STR markers, six were used to develop two multiplex PCRs. Additionally, three previously reported markers were selected for a third multiplex PCR. In total, 119 isolates were typed using these nine markers and 79 different genotypes were found. STR typing correlated well with WGS SNP typing, as isolates with the same STR genotype varied by 8 and 19 SNPs, while isolates that differed in all STR markers varied at least tens of thousands of SNPs. The STR typing assay was found to be specific for , stable in 100 subcloned generations, and comparable to SNP calling by WGS. In summary, this newly developed STR typing scheme is a fast, reliable, easy-to-interpret and cost-effective method compared to other typing methods. Moreover, the two newly developed multiplexes showed the same discriminatory power as all nine markers combined, indicating that multiplexes M3-1 and M9 are sufficient to type .
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http://dx.doi.org/10.1128/JCM.02032-21DOI Listing
November 2021

South Asian (Clade I) Candida auris meningitis in a paediatric patient in Iran with a review of the literature.

Mycoses 2021 Nov 15. Epub 2021 Nov 15.

Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.

Candida meningitis is a rare life-threatening yeast infection mostly involving immunocompromised or paediatric patients undergoing neurosurgical procedures or shunt placement. Due to difficulties in diagnosis because of diverse clinical manifestations, the number of patients affected is most likely underestimated. Therefore, the correct diagnosis may be delayed for months, and accurate species identification is highly recommended for administering appropriate antifungal therapy. We report the first case of fluconazole-resistant Candida auris meningitis in a paediatric patient in Iran. This strain was probably imported, as it genotypically belonged to Clade I from South Asia. Furthermore, we include a literature review of C auris meningitis cases, as the number of cases with C auris meningitis has increased with reports from the United Kingdom, India and Iran. This problem might increase further in the era of COVID-19 due to attrition of experienced healthcare personnel and a high workload of hospital healthcare workers. To understand the precise prevalence of this emerging multidrug resistance pathogen, epidemiological surveillance studies are urgently warranted.
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http://dx.doi.org/10.1111/myc.13396DOI Listing
November 2021

Multi-locus sequence typing reveals genotypic similarity in Nigerian AFLP1/VNI of environmental and clinical origin.

J Med Microbiol 2021 Oct;70(10)

Westerdijk Fungal Biodiversity Institute, Utrecht, The Netherlands.

Pigeon droppings are among the major environmental sources of AFLP1/VNI from where the organism infects susceptible humans and animals resulting in cryptococcosis. Until now, AFLP1B/VNII was the only molecular type reported in Nigeria. Effective clinical treatment of this infection has occasionally been stymied by the emergence of antifungal non-susceptible, and resistant strains of AFLP1/VNI.Pigeon droppings harbour and HIV/AIDS patients are among the susceptible population to develop cryptococcal infection. Epidemiological data on cryptococcal prevalence is limited in Nigeria.To investigate the environmental prevalence of in South-eastern Nigeria and compare the isolates with other lineages by using molecular and microbiological tools.A total of 500 pigeon droppings and 300 blood samples of HIV/AIDS patients were collected, respectively, from five market squares and three tertiary healthcare centres within the Nsukka area of South-eastern Nigeria. The antifungal susceptibility of the isolates to amphotericin B, fluconazole, 5-fluorocytosine, itraconazole, voriconazole, posaconazole, and isavuconazole was investigated based on the CLSI M27-A3 protocol. Yeasts were identified by MALDI-TOF MS, thereafter MLST was performed according to the International Society for Human and Animal Mycology (ISHAM) consensus scheme. was recovered from 6 (1.2 %) pigeon droppings and 6 (2 %) blood cultures of HIV/AIDS patients. Molecular analyses indicated that all cryptococcal isolates belong to serotype A and the AFLP1/VNI molecular type with sequence type (ST)32. Infection with was independent of sex and age of the patients investigated. All isolates were susceptible to the seven antifungal agents.This is the first report on the prevalence of AFLP1/VNI (ST32) in environmental and clinical samples from Nigeria. The antifungal susceptibility indicates that antifungal resistance by is yet a rare occurrence in Nigeria.
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http://dx.doi.org/10.1099/jmm.0.001440DOI Listing
October 2021

Diagnostic Allele-Specific PCR for the Identification of Clades.

J Fungi (Basel) 2021 Sep 13;7(9). Epub 2021 Sep 13.

Laboratory of Molecular Cell Biology, Department of Biology, Institute of Botany and Microbiology, KU Leuven, 3001 Leuven, Belgium.

is an opportunistic pathogenic yeast that emerged worldwide during the past decade. This fungal pathogen poses a significant public health threat due to common multidrug resistance (MDR), alarming hospital outbreaks, and frequent misidentification. Genomic analyses have identified five distinct clades that are linked to five geographic areas of origin and characterized by differences in several phenotypic traits such as virulence and drug resistance. Typing of strains and the identification of clades can be a powerful tool in molecular epidemiology and might be of clinical importance by estimating outbreak and MDR potential. As has caused global outbreaks, including in low-income countries, typing strains quickly and inexpensively is highly valuable. We report five allele-specific polymerase chain reaction (AS-PCR) assays for the identification of and each of the five described clades of based on conserved mutations in the internal transcribed spacer (ITS) rDNA region and a clade-specific gene cluster. This PCR method provides a fast, cheap, sequencing-free diagnostic tool for the identification of , clades, and potentially, the discovery of new clades.
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http://dx.doi.org/10.3390/jof7090754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471779PMC
September 2021

sp. nov. Causing Angioinvasive Abdominal Basidiobolomycosis.

J Fungi (Basel) 2021 Aug 12;7(8). Epub 2021 Aug 12.

Department of Microbiology and Immunology, Sultan Qaboos University Hospital, Muscat 123, Oman.

Human infectious fungal diseases are increasing, despite improved hygienic conditions. We present a case of gastrointestinal basidiobolomycosis (GIB) in a 20-year-old male with a history of progressively worsening abdominal pain. The causative agent was identified as a novel species. Validation of its novelty was established by analysis of the partial ribosomal operon of two isolates from different organs. Phylogeny of ITS and LSU rRNA showed that these isolates belonged to the genus positioned closely to and . Morphological and physiological data supported the identity of the species, which was named , with CBS 146281 as the holotype. The strains showed high minimum inhibitory concentrations (MICs) to fluconazole (>64 µg/mL), itraconazole and voriconazole (>16 µg/mL), anidulafungin and micafungin (>16 µg/mL), but had a low MIC to amphotericin B (1 µg/mL). The pathogenic role of in gastrointestinal disease is discussed. We highlight the crucial role of molecular identification of these rarely encountered opportunistic fungi.
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http://dx.doi.org/10.3390/jof7080653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400364PMC
August 2021

Disseminated Rhinocladiella mackenziei infection in a kidney transplant recipient: A case report and literature review.

J Mycol Med 2021 Aug 12;31(4):101196. Epub 2021 Aug 12.

Hamed Alessa Organ Transplant Center, Shuwaikh, Kuwait.

Rhinocladiella mackenziei is a rare fungal pathogen which belongs to a large group of pigmented fungi causing phaeohyphomycosis. R. mackenziei primarily infects the brain and leads to high fatality rates among both immunocompetent and immunocompromised individuals. Among solid organ transplant recipients, the infection may disseminate to extra-neuronal sites, necessitating comprehensive radiologic imaging. Here we describe a new case of R. mackenziei infection in a renal transplant patient involving the brain and renal allograft. She received liposomal amphotericin B and voriconazole but no surgical intervention. Ultimately, the patient died after two months of hospital stay. A review of all reported cases of transplant patients infected with R. mackenziei is also presented.
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http://dx.doi.org/10.1016/j.mycmed.2021.101196DOI Listing
August 2021

In vitro activities of 8 antifungal drugs against 126 clinical and environmental Exophiala isolates.

Mycoses 2021 Nov 23;64(11):1328-1333. Epub 2021 Aug 23.

Bioprocess Engineering and Biotechnology Graduate Program, Microbiology, Parasitology and Pathology Post-Graduation Program, Department of Basic Pathology, Federal University of Paraná, Curitiba, Brazil.

Background: Exophiala is the main genus of black fungi comprising numerous opportunistic species. Data on antifungal susceptibility of Exophiala isolates are limited, while infections are potentially fatal.

Materials And Methods: In vitro activities of eight antifungal drugs (AMB, five azoles, two echinocandins) against 126 clinical (n = 76) and environmental (n = 47) isolates from around the world were investigated. E. oligosperma (n = 58), E. spinifera (n = 33), E. jeanselmei (n = 14) and E. xenobiotica (n = 21) were included in our dataset.

Results: The resulting MIC s of all strains were as follows, in increasing order: posaconazole 0.063 μg/ml, itraconazole 0.125 μg/ml, voriconazole and amphotericin B 1 μg/ml, isavuconazole 2 μg/ml, micafungin and caspofungin 4 μg/ml, and fluconazole 64 μg/ml. Posaconazole, itraconazole and micafungin were the drugs with the best overall activity against Exophiala species. Fluconazole could not be considered as a treatment choice. No significant difference could be found among antifungal drug activities between these four species, neither in clinical nor in environmental isolates.

Conclusion: Antifungal susceptibility data for Exophiala spp. are crucial to improve the management of this occasionally fatal infection and the outcome of its treatment.
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http://dx.doi.org/10.1111/myc.13364DOI Listing
November 2021

Molecular typing and antifungal susceptibility study of Aspergillus spp. in intensive care unit (ICU) patients in Indonesia.

J Infect Dev Ctries 2021 07 31;15(7):1014-1020. Epub 2021 Jul 31.

Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

Introduction: Aspergillus exhibits a wide variation of susceptibility against antifungals according to genetic and environmental factors. Identification to the species level is necessary for appropriate treatment. Our objective was to determine the Aspergillus species involved in invasive pulmonary aspergillosis (IPA) among ICU patients in Jakarta, Indonesia.

Methodology: The incidence of IPA in ICU patients at six hospitals in Jakarta from October 2012 - January 2015 was investigated. It involved a collection of endotracheal aspirates (ETA), nasal swabs and environmental samples around the hospitals, phenotypic screening, molecular characterization, and antifungal susceptibility testing.

Results: Of the 405 patients investigated, 31 patients (7.7%) were diagnosed with putative IPA, from whom 45 Aspergillus isolates were collected. Aspergillus isolates were identified from pulmonary secretions in 24 patients, from nasal swabs in 7 patients and from both pulmonary secretions and nasal swabs in 7 patients. The phenotypic method showed 33 isolates of Aspergillus flavus (73.4%), nine Aspergillus fumigatus (20%), two Aspergillus niger (4.4%), and one Aspergillus nidulans (2.2%) isolate. Molecular identification showed 27 isolates of A. flavus (60.0%), eight isolates of A. fumigatus (17.8%), two isolates of A. niger (4.4%) and one isolate of A. nidulans (2.2%), while seven isolates (15.6%) were cryptic species or mixed isolates.

Conclusions: Susceptibility testing showed all isolates were susceptible to amphotericin B, azoles and micafungin. Aspergillus flavus was the main causative organism in IPA cases in Jakarta, followed by A. fumigatus.
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http://dx.doi.org/10.3855/jidc.13135DOI Listing
July 2021

Antifungal activity of nitroxoline against Candida auris isolates.

Clin Microbiol Infect 2021 Nov 7;27(11):1697.e7-1697.e10. Epub 2021 Jul 7.

Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Medical Faculty and University Hospital of Cologne, Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany; Institute for Medical Microbiology and Virology, University of Oldenburg, Oldenburg, Germany. Electronic address:

Objectives: To investigate the in vitro activity of nitroxoline against a molecularly characterized collection of clinical Candida auris isolates.

Methods: Thirty-five clinical isolates of C. auris from diverse sources representing all five different C. auris clades were included in the study. Nitroxoline activity was assessed using broth microdilution. Additionally, susceptibility testing by disc diffusion was assessed on RPMI-1640 and Müller-Hinton agar plates. Minimal inhibitory concentrations of the antifungals fluconazole, voriconazole, amphotericin B and anidulafungin were determined.

Results: Nitroxoline MICs ranged from 0.125 to 1 mg/L (MIC 0.25/0.5 mg/L). Compared with amphotericin B (MIC >1 mg/L in 4/35 isolates), anidulafungin (MIC >0.06 mg/L in 26/35 isolates) and fluconazole (MIC >4 mg/L in 31/35 isolates), in vitro activity of nitroxoline was high. Isolates belonging to clade I had marginally lower nitroxoline MICs (range 0.125-0.5 mg/L, mean MIC 0.375 mg/L) compared with clade III (range 0.5-1 mg/L, mean MIC 0.7 mg/L; p = 0.0094). The correlation of MIC and inhibition zones by disc diffusion was good when using RPMI-agar for disc diffusion, with a Pearson's correlation coefficient of -0.74 (95% CI -0.86 to -0.54).

Conclusions: Nitroxoline has excellent in vitro activity against C. auris isolates, with MICs of 0.125-1 mg/L (for comparison, the EUCAST breakpoint for uncomplicated urinary tract infection with Escherichia coli is ≤ 16 mg/L). It is an approved, well-tolerated antimicrobial that achieves high urinary concentrations after oral administration and could be a useful treatment option in C. auris candiduria.
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http://dx.doi.org/10.1016/j.cmi.2021.06.035DOI Listing
November 2021

ECMM/ISHAM recommendations for clinical management of COVID-19 associated mucormycosis in low- and middle-income countries.

Mycoses 2021 Sep 26;64(9):1028-1037. Epub 2021 Jul 26.

Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Reports are increasing on the emergence of COVID-19-associated mucormycosis (CAM) globally, driven particularly by low- and middle-income countries. The recent unprecedented surge of CAM in India has drawn worldwide attention. More than 28,252 mucormycosis cases are counted and India is the first country where mucormycosis has been declared a notifiable disease. However, misconception of management, diagnosing and treating this infection continue to occur. Thus, European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) felt the need to address clinical management of CAM in low- and middle-income countries. This article provides a comprehensive document to help clinicians in managing this infection. Uncontrolled diabetes mellitus and inappropriate (high dose or not indicated) corticosteroid use are the major predisposing factors for this surge. High counts of Mucorales spores in both the indoor and outdoor environments, and the immunosuppressive impact of COVID-19 patients as well as immunotherapy are possible additional factors. Furthermore, a hyperglycaemic state leads to an increased expression of glucose regulated protein (GRP- 78) in endothelial cells that may help the entry of Mucorales into tissues. Rhino-orbital mucormycosis is the most common presentation followed by pulmonary mucormycosis. Recommendations are focused on the early suspicion of the disease and confirmation of diagnosis. Regarding management, glycaemic control, elimination of corticosteroid therapy, extensive surgical debridement and antifungal therapy are the standards for proper care. Due to limited availability of amphotericin B formulations during the present epidemic, alternative antifungal therapies are also discussed.
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http://dx.doi.org/10.1111/myc.13335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447004PMC
September 2021

Two Cases in Germany with No Recent Contact to Foreign Healthcare-Epidemiological and Microbiological Investigations.

J Fungi (Basel) 2021 May 12;7(5). Epub 2021 May 12.

Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.

has become a global fungal public health threat. This multidrug-resistant yeast is associated with nosocomial intra- and interhospital transmissions causing healthcare-associated infections. Here, we report on two cases from Germany. The two patients stayed in Germany for a long time before was detected during their hospitalization. The patients were isolated in single rooms with contact precautions. No nosocomial transmissions were detected within the hospital. Both isolates exhibited high minimum inhibitory concentrations (MICs) of fluconazole and one isolate additionally high MICs against the echinocandins. Microsatellite genotyping showed that both strains belong to the South Asian clade. These two cases are examples for appropriate in-hospital care and infection control without further nosocomial spread. Awareness for this emerging, multidrug-resistant pathogen is justified and systematic surveillance in European health care facilities should be performed.
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http://dx.doi.org/10.3390/jof7050380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151845PMC
May 2021

Axillary Digital Thermometers uplifted a multidrug-susceptible Candida auris outbreak among COVID-19 patients in Brazil.

Mycoses 2021 Sep 7;64(9):1062-1072. Epub 2021 Jun 7.

Disciplina de Infectologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.

Objectives: To describe the first outbreak of Candida auris in Brazil, including epidemiological, clinical and microbiological data.

Methods: After the first Candida auris-colonised patient was diagnosed in a COVID-19 ICU at a hospital in Salvador, Brazil, a multidisciplinary team conducted a local C. auris prevalence investigation. Screening cultures for C. auris were collected from patients, healthcare workers and inanimate surfaces. Risk factors for C. auris colonisation were evaluated, and the fungemia episodes that occurred after the investigation were also analysed and described. Antifungal susceptibility of the C. auris isolates was determined, and they were genotyped with microsatellite analysis.

Results: Among body swabs collected from 47 patients, eight (n = 8/47, 17%) samples from the axillae were positive for C. auris. Among samples collected from inanimate surfaces, digital thermometers had the highest rate of positive cultures (n = 8/47, 17%). Antifungal susceptibility testing showed MICs of 0.5 to 1 mg/L for AMB, 0.03 to 0.06 mg/L for voriconazole, 2 to 4 mg/L for fluconazole and 0.03 to 0.06 mg/L for anidulafungin. Microsatellite analysis revealed that all C. auris isolates belong to the South Asian clade (Clade I) and had different genotypes. In multivariate analysis, having a colonised digital thermometer was the only independent risk factor associated with C. auris colonisation. Three episodes of C. auris fungemia occurred after the investigation, with 30-day attributable mortality of 33.3%.

Conclusions: Emergence of C. auris in Salvador, Brazil, may be related to local C. auris clade I closely related genotypes. Contaminated axillary monitoring thermometers may facilitate the dissemination of C. auris reinforcing the concept that these reusable devices should be carefully cleaned with an effective disinfectant or replaced by other temperature monitoring methods.
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http://dx.doi.org/10.1111/myc.13320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242760PMC
September 2021

MALDI-TOF MS characterisation, genetic diversity and antifungal susceptibility of Trichosporon species from Iranian clinical samples.

Mycoses 2021 Aug 1;64(8):918-925. Epub 2021 Jun 1.

Antimicrobial Resistance Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Trichosporonosis is an emerging fungal infection caused by Trichosporon species, a genus of yeast-like fungi, which are frequently encountered in human infections ranging from mild cutaneous lesions to fungemia in immunocompromised patients. The incidence of trichosporonosis has increased in recent years, owing to higher numbers of individuals at risk for this infection. Although amphotericin B, posaconazole and isavuconazole are generally effective against Trichosporon species, some isolates may have variable susceptibility to these antifungals.

Objectives: Herein, we evaluated the species distribution, genetic diversity and antifungal susceptibility profiles of Trichosporon isolates in Iran.

Methods: The yeasts were identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Phylogenetic analysis was performed based on amplified fragment length polymorphism (AFLP). The in vitro susceptibilities of eight antifungal agents were analysed using the Clinical and Laboratory Standards Institute broth microdilution methods.

Results: The isolates belonged to the species T asahii (n = 20), T japonicum (n = 4) and T faecale (n = 3). A dendrogram of the AFLP analysis demonstrated that T asahii and non-asahii Trichosporon strains (T japonicum and T faecale) are phylogenetically distinct. While voriconazole was the most active agent (GM MIC = 0.075 μg/ml), high fluconazole MICs (8 μg/ml) were observed for a quarter of Trichosporon isolates. The GM MIC value of amphotericin B for T asahii and non-asahii Trichosporon species was 0.9 μg/ml.

Conclusions: The distribution and antifungal susceptibility patterns of the identified Trichosporon species could inform therapeutic choices for treating these emerging life-threatening fungi.
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http://dx.doi.org/10.1111/myc.13306DOI Listing
August 2021

Antifungal Susceptibility and Mutations in the Squalene Epoxidase Gene in Dermatophytes of the Trichophyton mentagrophytes Species Complex.

Antimicrob Agents Chemother 2021 07 16;65(8):e0005621. Epub 2021 Jul 16.

Department of Medical Mycology, Institute of Dermatology, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing, China.

During the past decade, a prolonged and serious outbreak of dermatophytosis due to a terbinafine-resistant novel species in the Trichophyton mentagrophytesT. interdigitale complex has been ongoing in India, and it has spread to several European countries. The objective of this study was to investigate the molecular background of the squalene epoxidase () gene in order to understand the risk of emergence and spread of multiresistance in dermatophytes. Antifungal susceptibility to fluconazole, griseofulvin, itraconazole, ketoconazole, miconazole, naftifine, sertaconazole, and terbinafine was tested in 135 isolates from India, China, Australia, Germany, and The Netherlands. Based on the latest taxonomic insights, strains were identified as three species: T. mentagrophytes ( = 35), T. indotineae ( = 64, representing the Indian clone), and T. interdigitale ( = 36). High MICs of terbinafine (>16 mg/liter) were found in 34 (53%) isolates. These isolates showed an amino acid substitution in the 397th position of the gene. Elevated MICs of terbinafine (0.5 mg/liter) were noted in 2 (3%) isolates; these isolates lead to PheVal and LeuSer of the gene. The stability of the effect of the mutations was proven by serial transfer on drug-free medium. LysAsn and LeuPhe substitutions were found in susceptible T. mentagrophytes strains. The PheLeu/AlaThr double mutant showed higher MIC values for triazoles. High MICs of terbinafine are as yet limited to and are unlikely to be distributed throughout the T. mentagrophytes species complex by genetic exchange.
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http://dx.doi.org/10.1128/AAC.00056-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284460PMC
July 2021

Environmental Detection of SARS-CoV-2 Virus RNA in Health Facilities in Brazil and a Systematic Review on Contamination Sources.

Int J Environ Res Public Health 2021 04 6;18(7). Epub 2021 Apr 6.

Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba 81530-000, Brazil.

SARS-CoV-2 environmental monitoring can track the rate of viral contamination and can be used to establish preventive measures. This study aimed to detect by RT-PCR the presence of SARS-CoV-2 from inert surface samples in public health settings with a literature review about surface contamination and its burden on spread virus. Samples were collected from health settings in Curitiba, Brazil, between July and December 2020. A literature review was conducted using PRISMA. A total of 711 environmental surface samples were collected from outpatient areas, dental units, doctors' offices, COVID-19 evaluation areas, and hospital units, of which 35 (4.9%) were positive for SARS-CoV-2 RNA. The frequency of environmental contamination was higher in primary care units than in hospital settings. The virus was detected on doctors' personal items. Remarkably, the previously disinfected dental chair samples tested positive. These findings agree with those of other studies in which SARS-CoV-2 was found on inanimate surfaces. Detection of SARS-CoV-2 RNA on surfaces in public health settings, including those not meant to treat COVID-19, indicates widespread environmental contamination. Therefore, the intensification of disinfection measures for external hospital areas may be important for controlling community COVID-19 dissemination.
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http://dx.doi.org/10.3390/ijerph18073824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038740PMC
April 2021

Taxonomy of the Trichophyton mentagrophytes/T. interdigitale Species Complex Harboring the Highly Virulent, Multiresistant Genotype T. indotineae.

Mycopathologia 2021 Jun 13;186(3):315-326. Epub 2021 Apr 13.

Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education of Guizhou & Key Laboratory of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, China.

A severe outbreak of highly virulent and multi-resistant dermatophytosis by species in the Trichophyton mentagrophytes/T. interdigitale complex is ongoing in India. The correct identity of the etiologic agent is a much-debated issue. In order to define species limits, a taxonomic study was undertaken combining molecular, morphological, and physiological characteristics as evidence of classification. Molecular characteristics show that T. mentagrophytes s. str. and T. interdigitale s. str. can be distinguished with difficulty from each other, but are unambiguously different from the Indian genotype, T. indotineae by sequences of the HMG gene. The entities were confirmed by multilocus analysis using tanglegrams. Phenotypic characters of morphology and physiology are not diagnostic, but statistically significant differences are observed between the molecular siblings. These properties may be drivers of separate evolutionary trends. Trichophyton mentagrophytes represents the ancestral, homothallic cloud of genotypes with a probable geophilic lifestyle, while T. indotineae and T. interdigitale behave as anthropophilic, clonal offshoots. The origin of T. indotineae, which currently causes a significant public health problem, is zoonotic, and its emergence is likely due to widespread misuse of antifungals.
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http://dx.doi.org/10.1007/s11046-021-00544-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249266PMC
June 2021

Are We Ready for Nosocomial Infections? Rapid Identification and Antifungal Resistance Detection Using MALDI-TOF Mass Spectrometry May Be the Answer.

Front Cell Infect Microbiol 2021 16;11:645049. Epub 2021 Mar 16.

Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

The occurrence of multidrug-resistant isolates and the increased mortality associated with invasive infections or outbreaks due to this species have been reported in many healthcare settings. Therefore, accurate and rapid identification at the species level of clinical isolates as well as their timely differentiation as susceptible or resistant to antifungal drugs is mandatory. Aims of the present study were to implement the MALDI-TOF mass spectrometry (MS) Bruker Daltonics Biotyper database with spectrum profiles and to develop a fast and reproducible MS assay for detecting anidulafungin (AFG) resistance in isolates. After creation of main spectra, a score-oriented dendrogram was generated from hierarchical cluster analysis, including spectra of isolates from and other (, , , , and ) or non- () species. Cluster analysis allowed to group and classify the isolates according to their species designation. Then, a three-hour incubation antifungal susceptibility testing (AFST) assay was developed. Spectra obtained at null, intermediate, or maximum AFG concentrations were used to create composite correlation index matrices for eighteen isolates included in the study. All six resistant isolates were detected as resistant whereas 11 of 12 susceptible isolates were detected as susceptible by the MS-AFST assay. In conclusion, our MS-based assay offers the possibility of rapidly diagnosing and appropriately treating patients with infection.
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http://dx.doi.org/10.3389/fcimb.2021.645049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007968PMC
July 2021

Clade-specific chromosomal rearrangements and loss of subtelomeric adhesins in Candida auris.

Genetics 2021 05;218(1)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Candida auris is an emerging fungal pathogen of rising concern due to global spread, the ability to cause healthcare-associated outbreaks, and antifungal resistance. Genomic analyses revealed that early contemporaneously detected cases of C. auris were geographically stratified into four major clades. While Clades I, III, and IV are responsible for ongoing outbreaks of invasive and multidrug-resistant infections, Clade II, also termed the East Asian clade, consists primarily of cases of ear infection, is often susceptible to all antifungal drugs, and has not been associated with outbreaks. Here, we generate chromosome-level assemblies of twelve isolates representing the phylogenetic breadth of these four clades and the only isolate described to date from Clade V. This Clade V genome is highly syntenic with those of Clades I, III, and IV, although the sequence is highly divergent from the other clades. Clade II genomes appear highly rearranged, with translocations occurring near GC-poor regions, and large subtelomeric deletions in most chromosomes, resulting in a substantially different karyotype. Rearrangements and deletion lengths vary across Clade II isolates, including two from a single patient, supporting ongoing genome instability. Deleted subtelomeric regions are enriched in Hyr/Iff-like cell-surface proteins, novel candidate cell wall proteins, and an ALS-like adhesin. Cell wall proteins from these families and other drug-related genes show clade-specific signatures of selection in Clades I, III, and IV. Subtelomeric dynamics and the conservation of cell surface proteins in the clades responsible for global outbreaks causing invasive infections suggest an explanation for the different phenotypes observed between clades.
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http://dx.doi.org/10.1093/genetics/iyab029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128392PMC
May 2021

Evaluation of DermaGenius resistance real-time polymerase chain reaction for rapid detection of terbinafine-resistant Trichophyton species.

Mycoses 2021 Jul 18;64(7):721-726. Epub 2021 May 18.

Medical Mycology Unit, Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, India.

Background: Treatment-resistant dermatophytosis caused by Trichophyton mentagrophytes/interdigitale complex has emerged as a global public health threat, particularly in endemic countries like India and has spread to many other countries. This veritable spread is alarming due to increase in resistance to terbinafine, which targets the ergosterol biosynthetic pathway by inhibiting the enzyme squalene epoxidase (SQLE). About two third of studies worldwide have reported amino acid substitutions Phe397Leu and Leu393Phe in the SQLE protein to be responsible for high terbinafine MICs.

Objectives: We evaluated the efficacy of the newly developed DermaGenius Resistance real-time PCR assay to rapidly identify Trichophyton isolates harbouring most common SQLE mutant (Phe397Leu and Leu393Phe) conferring high terbinafine resistance from wild-type susceptible isolates.

Methods: A total of 97 Trichophyton isolates confirmed by ITS sequencing as T. mentagrophytes/interdigitale (recently named T. indotineae n = 90), T. rubrum/T. soudanense (n = 3), T mentagrophytes (n = 2) and T tonsurans (n = 2) were analysed to evaluate DermaGenius Resistance real-time PCR assay. All 40 T. indotineae isolates exhibiting amino acid substitutions Phe397Leu or Leu393Phe identified by SQLE gene sequencing were evaluated for detection of non-wild-type strains by real-time PCR. Antifungal susceptibility testing for terbinafine was done by CLSI microbroth dilution method.

Results: All terbinafine-resistant isolates harbouring amino acid substitutions Phe397Leu or Leu393Phe in SQLE gene were correctly recorded as SQLE mutants by the DermaGenius Resistance real-time PCR assay.

Conclusions: The DermaGenius Resistance real-time PCR assay effectively identified Trichophyton species and distinguished wild-type from SQLE mutant genotype that harbour Phe397Leu and Leu393Phe amino acid substitutions.
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http://dx.doi.org/10.1111/myc.13271DOI Listing
July 2021

Comparison of Two Commercially Available qPCR Kits for the Detection of .

J Fungi (Basel) 2021 Feb 22;7(2). Epub 2021 Feb 22.

Institute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne, University of Cologne, 50935 Cologne, Germany.

is an emerging pathogen with resistance to many commonly used antifungal agents. Infections with require rapid and reliable detection methods to initiate successful medical treatment and contain hospital outbreaks. Conventional identification methods are prone to errors and can lead to misidentifications. PCR-based assays, in turn, can provide reliable results with low turnaround times. However, only limited data are available on the performance of commercially available assays for detection. In the present study, the two commercially available PCR assays ID (OLM, Newcastle Upon Tyne, UK) and Fungiplex RUO Real-Time PCR (Bruker, Bremen, Germany) were challenged with 29 isolates from all five clades and eight other species as controls. ID reliably detected with a limit of detection (LoD) of 1 genome copies/reaction. However, false positive results were obtained with high DNA amounts of the closely related species and . The Fungiplex RUO Real-Time PCR kit detected with an LoD of 9 copies/reaction. No false positive results were obtained with this assay. In addition, could also be detected in human blood samples spiked with pure fungal cultures by both kits. In summary, both kits could detect -DNA at low DNA concentrations but differed slightly in their limits of detection and specificity.
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http://dx.doi.org/10.3390/jof7020154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926799PMC
February 2021

Genetic and Phenotypic Characterization of in-Host Developed Azole-Resistant Isolates.

J Fungi (Basel) 2021 Feb 25;7(3). Epub 2021 Feb 25.

Department of Medical Microbiology, Radboud University Medical Center, 6525 GANijmegen, The Netherlands.

is a pathogenic fungal species that can cause pulmonary aspergillosis, and triazole compounds are used for the treatment of these infections. Prolonged exposure to azoles may select for compensatory mutations in the genome, resulting in azole resistance. Here, we characterize a series of 11 isogenic strains isolated from a patient with pulmonary aspergillosis. Over a period of three months, the initially azole-susceptible strain developed itraconazole and voriconazole resistance. Short tandem repeat analysis and whole-genome sequencing revealed the high genetic relatedness of all isolates, indicating an infection with one single isolate. In contrast, the isolates were macroscopically highly diverse, suggesting an adaptation to the environment due to (epi)genetic changes. The whole-genome sequencing of susceptible and azole-resistant strains showed a number of mutations that might be associated with azole resistance. The majority of resistant strains contain a Y119F mutation in the gene, which corresponds to the Y121F mutation found in . One azole-resistant strain demonstrated a divergent set of mutations, including a V99A mutation in a major facilitator superfamily (MSF) multidrug transporter (AFLA 083950).
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http://dx.doi.org/10.3390/jof7030164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996152PMC
February 2021

Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology.

Lancet Infect Dis 2021 08 16;21(8):e246-e257. Epub 2021 Feb 16.

Department of Microbiology, University of Colombo, Colombo, Sri Lanka.

With increasing numbers of patients needing intensive care or who are immunosuppressed, infections caused by moulds other than Aspergillus spp or Mucorales are increasing. Although antifungal prophylaxis has shown effectiveness in preventing many invasive fungal infections, selective pressure has caused an increase of breakthrough infections caused by Fusarium, Lomentospora, and Scedosporium species, as well as by dematiaceous moulds, Rasamsonia, Schizophyllum, Scopulariopsis, Paecilomyces, Penicillium, Talaromyces and Purpureocillium species. Guidance on the complex multidisciplinary management of infections caused by these pathogens has the potential to improve prognosis. Management routes depend on the availability of diagnostic and therapeutic options. The present recommendations are part of the One World-One Guideline initiative to incorporate regional differences in the epidemiology and management of rare mould infections. Experts from 24 countries contributed their knowledge and analysed published evidence on the diagnosis and treatment of rare mould infections. This consensus document intends to provide practical guidance in clinical decision making by engaging physicians and scientists involved in various aspects of clinical management. Moreover, we identify areas of uncertainty and constraints in optimising this management.
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http://dx.doi.org/10.1016/S1473-3099(20)30784-2DOI Listing
August 2021

COVID-19-associated pulmonary aspergillosis: a prospective single-center dual case series.

Mycoses 2021 Apr 16;64(4):457-464. Epub 2021 Feb 16.

Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as an invasive fungal disease, often affecting previously immunocompetent, mechanically ventilated, intensive care unit (ICU) patients. Incidence rates of 3.8%-33.3% have been reported depending on the geographic area, with high (47%) mortality.

Objectives: Here, we describe a single-centre prospective case series with CAPA cases from both the first (March-May, n = 5/33) and second (mid-September through mid-December, n = 8/33) COVID-19 wave at a 500-bed teaching hospital in the Netherlands.

Patients/methods: In the first COVID-19 wave, a total of 265 SARS-CoV-2 PCR-positive patients were admitted to our hospital of whom 33 needed intubation and mechanical ventilation. In the second wave, 508 SARS-CoV-2 PCR-positive patients were admitted of whom 33 needed mechanical ventilation. Data were prospectively collected.

Results: We found a significant decrease in COVID-19 patients needing mechanical ventilation in the ICU in the second wave (p < .01). From these patients, however, a higher percentage were diagnosed with CAPA (24.2% vs 15.2%), although not significant (p = .36). All CAPA patients encountered in the second wave received dexamethasone. Mortality between both groups was similarly high (40%-50%). Moreover, we found environmental TR /L98H azole-resistant Aspergillus fumigatus isolates in two separate patients.

Conclusions: In this series, 19.7% (n = 13/66) of mechanically ventilated SARS-CoV-2 patients were diagnosed with CAPA. In addition, we found a significant reduction in COVID-19 patients needing mechanical ventilation on the ICU in the second wave. Numbers are too small to determine whether there is a true difference in CAPA incidence in mechanically ventilated patients between the two waves, and whether it could be attributed to dexamethasone SARS-CoV-2 therapy.
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http://dx.doi.org/10.1111/myc.13254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986084PMC
April 2021

COVID-19-Associated Pulmonary Aspergillosis, March-August 2020.

Emerg Infect Dis 2021 4;27(4):1077-1086. Epub 2021 Feb 4.

Pneumonia caused by severe acute respiratory syndrome coronavirus 2 emerged in China at the end of 2019. Because of the severe immunomodulation and lymphocyte depletion caused by this virus and the subsequent administration of drugs directed at the immune system, we anticipated that patients might experience fungal superinfection. We collected data from 186 patients who had coronavirus disease-associated pulmonary aspergillosis (CAPA) worldwide during March-August 2020. Overall, 182 patients were admitted to the intensive care unit (ICU), including 180 with acute respiratory distress syndrome and 175 who received mechanical ventilation. CAPA was diagnosed a median of 10 days after coronavirus disease diagnosis. Aspergillus fumigatus was identified in 80.3% of patient cultures, 4 of which were azole-resistant. Most (52.7%) patients received voriconazole. In total, 52.2% of patients died; of the deaths, 33.0% were attributed to CAPA. We found that the cumulative incidence of CAPA in the ICU ranged from 1.0% to 39.1%.
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http://dx.doi.org/10.3201/eid2704.204895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007287PMC
April 2021

Colonisation and Transmission Dynamics of among Chronic Respiratory Diseases Patients Hospitalised in a Chest Hospital, Delhi, India: A Comparative Analysis of Whole Genome Sequencing and Microsatellite Typing.

J Fungi (Basel) 2021 Jan 26;7(2). Epub 2021 Jan 26.

Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, India.

is a nosocomial pathogen responsible for an expanding global public health threat. This ascomycete yeast has been frequently isolated from hospital environments, representing a significant reservoir for transmission in healthcare settings. Here, we investigated the relationships among isolates from patients with chronic respiratory diseases admitted in a chest hospital and from their fomites, using whole-genome sequencing (WGS) and multilocus microsatellite genotyping. Overall, 37.5% ( = 12/32) patients developed colonisation by including 9.3% of the screened patients that were colonised at the time of admission and 75% remained colonised till discharge. Furthermore, 10% of fomite samples contained in rooms about 8.5 days after colonised patients were admitted. WGS and microsatellite typing revealed that multiple strains contaminated the fomites and colonised different body sites of patients. Notably, 37% of isolates were resistant to amphotericin B and a novel amino acid substitution, G145D in gene, was detected in all amphotericin B resistant isolates. In addition, 55% of isolates had two copies of the gene. Our results suggest significant genetic and ecological diversities of in healthcare setting. The WGS and microsatellite genotyping methods provided complementary results in genotype identification.
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http://dx.doi.org/10.3390/jof7020081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910912PMC
January 2021

Ruling out underlying infection in 200 presumed aseptic knee and hip revision arthroplasties using a multiplex PCR system.

Eur J Clin Microbiol Infect Dis 2021 Jun 22;40(6):1283-1290. Epub 2021 Jan 22.

Department of Orthopaedic Surgery, Prosthetic Joint Infection Unit, Sint Maartenskliniek, Nijmegen, The Netherlands.

Ruling out an infection in one-stage knee and hip revisions for presumed aseptic failure by conventional tissue cultures takes up to 14 days. Multiplex polymerase chain reaction (mPCR) is a quick test (4-5 h) for detecting pathogens. The purpose of this study was to evaluate the diagnostic accuracy of an automated mPCR of synovial fluid obtained intraoperatively in unsuspected knee and hip revisions. A prospective study was conducted with 200 patients undergoing a one-stage knee or hip revision. Synovial fluid was analyzed with the mPCR Unyvero implant and tissue infection G2 cartridge (U-ITI G2) system and compared to intraoperative tissue cultures. The primary outcome measure was the diagnostic accuracy, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), of the mPCR U-ITI G2 system compared to conventional cultures. In the knee revision group, there were no patients with a positive mPCR in combination with positive cultures. This resulted in a non-calculable sensitivity and PPV. The specificity and NPV in the knee revision group of the mPCR compared to tissue cultures was 96.8% and 96.8%, respectively. In the hip revision group, the sensitivity, specificity, PPV, and NPV of the mPCR compared to tissue cultures was 36.4%, 96.6%, 57.1%, and 92.5%, respectively. Sixteen mismatches occurred between the mPCR and tissue cultures. The mPCR U-ITI G2 system is a quick and reliable synovium fluid test for ruling out infection in presumed aseptic knee and hip revisions with a high NPV compared with tissue cultures, although some mismatches were observed. Periprosthetic tissue cultures are still advised as back-up for false negative and positive mPCR test results.
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http://dx.doi.org/10.1007/s10096-021-04155-zDOI Listing
June 2021

Antifungal Activity of a Medical-Grade Honey Formulation against .

J Fungi (Basel) 2021 Jan 13;7(1). Epub 2021 Jan 13.

Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital (CWZ), 6532 SZ Nijmegen, The Netherlands.

is a pathogenic yeast causing outbreaks in intensive care units with high mortality rates. The treatment of colonization is challenging due to high resistance rates. A potential alternative antifungal treatment is medical-grade honey. In this study the susceptibility of and other species to the medical-grade honey-based formulation L-Mesitran Soft was investigated. The medical-grade honey formulation reduced the growth of and other species in a dose-dependent manner. This inhibition was not only due to the honey component, as treatment with an identical concentration of this component only was less effective and even stimulated the growth of and , supporting the interpretation that supplements in the medical-grade honey formulation enhanced the antimicrobial activity. Increasing the concentration of the honey component to 40%, as is also present in an undiluted medical-grade honey formulation, lead to a 1- to 4-log inhibition of all species. Unprocessed local honey reduced the growth of nearly all species more strongly than medical-grade honey. ' susceptibility to the medical-grade honey formulation did not depend on geographic origin or resistance profile, although the multiresistant isolates tended to be more susceptible. Altogether, medical-grade honey formulation has a strong antifungal activity against and other species. Future studies should demonstrate whether the treatment of open wounds or skin colonized with is feasible and effective in the clinical setting.
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http://dx.doi.org/10.3390/jof7010050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828376PMC
January 2021

In vitro activity of the novel antifungal olorofim against dermatophytes and opportunistic moulds including Penicillium and Talaromyces species.

J Antimicrob Chemother 2021 04;76(5):1229-1233

Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.

Objectives: Olorofim is a novel antifungal agent with in vitro activity against Aspergillus and other opportunistic moulds. We investigated the in vitro activity of olorofim against a range of filamentous fungi comprising isolates of Aspergillus species, Scedosporium species, Alternaria alternata, dermatophytes, including terbinafine- and multidrug-resistant Trichophyton species, and Penicillium/Talaromyces species originating from patients in North India.

Methods: Antifungal susceptibility of olorofim was tested against 241 mould isolates of Penicillium/Talaromyces species, Trichophyton species, A. fumigatus and cryptic Aspergillus species, Scedosporium species, and Alternaria alternata using CLSI broth microdilution. The comparators were five systemic azoles, amphotericin B, terbinafine, and luliconazole.

Results: Overall, olorofim showed highly potent in vitro activity against dermatophytes and opportunistic moulds (MIC range of 0.004-0.125 mg/L) except for Alternaria alternata. Penicillium, and Talaromyces species and Trichophyton species exhibited a low geometric mean (GM) MIC (GM 0.027 mg/L and 0.015 mg/L, respectively) of olorofim. Importantly, a 2-12 dilution step decrease in in vitro activity of olorofim as compared with azoles was observed against Penicillium and Talaromyces. Notably, olorofim displayed potent in vitro activity against Trichophyton isolates including terbinafine-resistant and azole-resistant Trichophyton mentagrophytes/interdigitale with a modal MIC value of 0.008 mg/L. Further, azole-resistant A. fumigatus isolates harbouring mutations in azole target Cyp51A genes and several cryptic aspergilli displayed low MICs (range 0.004-0.03 mg/L) of olorofim. However, no in vitro activity of olorofim against Alternaria alternata was observed.

Conclusions: The potent in vitro activity of olorofim against drug-resistant dermatophytes and opportunistic moulds is promising, warranting evaluation of the clinical utility of olorofim.
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http://dx.doi.org/10.1093/jac/dkaa562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050765PMC
April 2021

Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance.

Lancet Infect Dis 2021 06 14;21(6):e149-e162. Epub 2020 Dec 14.

Faculty of Medicine, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany; Department I of Internal Medicine, European Excellence Center for Medical Mycology (ECMM), University Hospital Cologne, Cologne, Germany; Clinical Trials Centre Cologne, ZKS Köln, Cologne, Germany; German Center for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany. Electronic address:

Severe acute respiratory syndrome coronavirus 2 causes direct damage to the airway epithelium, enabling aspergillus invasion. Reports of COVID-19-associated pulmonary aspergillosis have raised concerns about it worsening the disease course of COVID-19 and increasing mortality. Additionally, the first cases of COVID-19-associated pulmonary aspergillosis caused by azole-resistant aspergillus have been reported. This article constitutes a consensus statement on defining and managing COVID-19-associated pulmonary aspergillosis, prepared by experts and endorsed by medical mycology societies. COVID-19-associated pulmonary aspergillosis is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Recommended first-line therapy is either voriconazole or isavuconazole. If azole resistance is a concern, then liposomal amphotericin B is the drug of choice. Our aim is to provide definitions for clinical research and up-to-date recommendations for clinical management of the diagnosis and treatment of COVID-19-associated pulmonary aspergillosis.
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http://dx.doi.org/10.1016/S1473-3099(20)30847-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833078PMC
June 2021
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