Need to re‐look cut‐off of Aspergillus Specific IgE Levels in Children with ABPA
Manvi Singh Anil Chauhan Nandini Paul Nishant Jaiswal Shreya Singh Arunaloke Chakrabarti Meenu Singh
First published: 01 June 2019 https://doi.org/10.1111/myc.12949
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/myc.12949
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Abstract
Background
The cut‐offs for total and specific IgE used for diagnosing ABPA in children have been adopted from adult literature and have not been validated in the pediatric population.
Objective
To establish the ideal cut‐offs of Total IgE and Aspergillus Specific IgE for the diagnosis of ABPA in children.
Methods
This study was a prospective observational case‐control study, conducted in a tertiary care hospital in North India, enrolling 140 children with partly controlled and uncontrolled asthma. Seventy children had ABPA based on the Rosenberg‐Patterson Criteria (Cases) whereas 70 children were without ABPA(Controls). All children were subjected to clinical examination and investigations like Absolute eosinophil count, Total IgE, Aspergillus Specific IgE, Aspergillus Skin Prick Test, and Radiological tests. ROC curve analysis was done to determine the ideal cut‐offs of Total and specific IgE to diagnose ABPA.
Results
The ROC curve analysis determined 1204IU/L as the cut‐off value of total IgE with a sensitivity of 79.7% (95%CI 68.31 to 88.44%) and specificity of 53.1% (95%CI 40.23 to 65.7). The ROC analysis of specific IgE levels of children with ABPA determined the cut‐off value of 0.49 KAU/L with a sensitivity of 94.03% (95%CI 85.41 to 98.35) and specificity of88.89% (95%CI 75.94 to 96.29%).
Conclusion
We propose that the cut‐offs of total and specific IgE need to be relooked in the pediatric population. Cut‐offs of Total IgE as 1204 IU/L and for Aspergillus‐specific IgE as 0.49KAU/L seem appropriate. Large multicentric studies should be conducted to determine the ideal values for diagnosing pediatric ABPA.
This article is protected by copyright. All rights reserved.
Manvi Singh Anil Chauhan Nandini Paul Nishant Jaiswal Shreya Singh Arunaloke Chakrabarti Meenu Singh
First published: 01 June 2019 https://doi.org/10.1111/myc.12949
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/myc.12949
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Abstract
Background
The cut‐offs for total and specific IgE used for diagnosing ABPA in children have been adopted from adult literature and have not been validated in the pediatric population.
Objective
To establish the ideal cut‐offs of Total IgE and Aspergillus Specific IgE for the diagnosis of ABPA in children.
Methods
This study was a prospective observational case‐control study, conducted in a tertiary care hospital in North India, enrolling 140 children with partly controlled and uncontrolled asthma. Seventy children had ABPA based on the Rosenberg‐Patterson Criteria (Cases) whereas 70 children were without ABPA(Controls). All children were subjected to clinical examination and investigations like Absolute eosinophil count, Total IgE, Aspergillus Specific IgE, Aspergillus Skin Prick Test, and Radiological tests. ROC curve analysis was done to determine the ideal cut‐offs of Total and specific IgE to diagnose ABPA.
Results
The ROC curve analysis determined 1204IU/L as the cut‐off value of total IgE with a sensitivity of 79.7% (95%CI 68.31 to 88.44%) and specificity of 53.1% (95%CI 40.23 to 65.7). The ROC analysis of specific IgE levels of children with ABPA determined the cut‐off value of 0.49 KAU/L with a sensitivity of 94.03% (95%CI 85.41 to 98.35) and specificity of88.89% (95%CI 75.94 to 96.29%).
Conclusion
We propose that the cut‐offs of total and specific IgE need to be relooked in the pediatric population. Cut‐offs of Total IgE as 1204 IU/L and for Aspergillus‐specific IgE as 0.49KAU/L seem appropriate. Large multicentric studies should be conducted to determine the ideal values for diagnosing pediatric ABPA.
This article is protected by copyright. All rights reserved.
Posaconazole therapeutic drug monitoring in clinical practice and longitudinal analysis of the effect of routine laboratory measurements on posaconazole concentrations
Anne‐Grete Märtson Anette Veringa Edwin R. van den Heuvel Martijn Bakker Daan Touw Tjip S. van der Werf Lambert F. R. Span Jan‐Willem C. Alffenaar
First published: 30 May 2019 https://doi.org/10.1111/myc.12948
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/myc.12948
The copyright line for this article was changed on 4 June 2019 after original online publication.
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Abstract
Background
Posaconazole is indicated for prophylaxis and treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) of posaconazole is used to optimize drug exposure. The aim of this study was to analyse and describe the TDM practices and exposure of posaconazole tablets.
Materials/methods
Patients who received posaconazole for treatment or prophylaxis of fungal infections were included in the study. The following therapeutic window was defined: if concentration was low (<0.7mg/L for prophylaxis or <1.5 mg/L for treatment) or high (>3.75mg/L) the hospital pharmacist provided the physician with dosage advice, which implementation to patient care was analysed. A longitudinal analysis was performed to analyse if different confounding variables had an effect on posaconazole concentrations.
Results
Forty‐seven patients were enrolled resulting in 217 posaconazole trough concentrations. A median of 3 (IQR 1‐7) samples were measured per patient. The median concentration was 1.7 mg/L (IQR 0.8‐2.7) for prophylaxis and 1.76 mg/L (IQR 1.3‐2.3) for treatment. Overall 78 posaconazole concentrations were out of the therapeutic window. For 45 (54%) of these concentrations a dosage change was recommended. In 54 (25%) of all measured posaconazole concentrations resulted in recommendation for dosage alteration. In the longitudinal analysis the laboratory markers and patient baseline variables did not have an effect on posaconazole concentrations.
Conclusions
Adequate posaconazole exposure was shown in in 64% (affected 28 patients) of the measured concentrations. TDM practice of posaconazole can be improved by increasing the implementation rate of dose recommendation by a multidisciplinary antifungal stewardship team.
This article is protected by copyright. All rights reserved.
Anne‐Grete Märtson Anette Veringa Edwin R. van den Heuvel Martijn Bakker Daan Touw Tjip S. van der Werf Lambert F. R. Span Jan‐Willem C. Alffenaar
First published: 30 May 2019 https://doi.org/10.1111/myc.12948
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/myc.12948
The copyright line for this article was changed on 4 June 2019 after original online publication.
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Abstract
Background
Posaconazole is indicated for prophylaxis and treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) of posaconazole is used to optimize drug exposure. The aim of this study was to analyse and describe the TDM practices and exposure of posaconazole tablets.
Materials/methods
Patients who received posaconazole for treatment or prophylaxis of fungal infections were included in the study. The following therapeutic window was defined: if concentration was low (<0.7mg/L for prophylaxis or <1.5 mg/L for treatment) or high (>3.75mg/L) the hospital pharmacist provided the physician with dosage advice, which implementation to patient care was analysed. A longitudinal analysis was performed to analyse if different confounding variables had an effect on posaconazole concentrations.
Results
Forty‐seven patients were enrolled resulting in 217 posaconazole trough concentrations. A median of 3 (IQR 1‐7) samples were measured per patient. The median concentration was 1.7 mg/L (IQR 0.8‐2.7) for prophylaxis and 1.76 mg/L (IQR 1.3‐2.3) for treatment. Overall 78 posaconazole concentrations were out of the therapeutic window. For 45 (54%) of these concentrations a dosage change was recommended. In 54 (25%) of all measured posaconazole concentrations resulted in recommendation for dosage alteration. In the longitudinal analysis the laboratory markers and patient baseline variables did not have an effect on posaconazole concentrations.
Conclusions
Adequate posaconazole exposure was shown in in 64% (affected 28 patients) of the measured concentrations. TDM practice of posaconazole can be improved by increasing the implementation rate of dose recommendation by a multidisciplinary antifungal stewardship team.
This article is protected by copyright. All rights reserved.
Mating genotypes and susceptibility profiles of clinical isolates of Candida glabrata from Turkey
Engin Kaplan Deniz Aktaş Şükran Önder Banu Metin Aylin Döğen Yasemin Oz Macit Ilkit
First published: 28 May 2019 https://doi.org/10.1111/myc.12945
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/myc.12945
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Abstract
Background
The sexual cycle of Candida glabrata is not known; however, genomic evidence is indicative of recombination among subpopulations and the genome harbors genes necessary for undergoing mating and meiosis, which may increase fitness. The relationship between specific mating type‐like (MTL) loci and antifungal susceptibility is not well understood in C. glabrata.
Objectives
We investigated different combinations of clinical C. glabrata isolate mating types and their antifungal susceptibility profiles.
Methods
Allele profiles of the mating genes of 103 clinical C. glabrata isolates were identified and their antifungal susceptibility to azoles, echinocandins, and amphotericin B was compared.
Results
The majority (88.3%) of screened isolates harboured the a allele in the locus. The MTL1, MTL2, and MTL3 loci harbored a (88.3%), a (95.1%), and α (71.8%) alleles, respectively. The C. glabrata isolates were susceptible to echinocandins but displayed high minimal inhibitory concentrations (MICs) for azoles. The MIC ranges and MIC90 values of all isolates were 1.0–≥64 and 8.0 μg mL−1 for fluconazole, 0.06–≥16.0 and 0.5 μg mL−1 for voriconazole, 0.06–≥16.0 and 1.0 μg mL−1 for posaconazole, ≤0.015–0.06, and 0.03 μg mL−1 for caspofungin, ≤0.015–0.06 and 0.015 μg mL−1 for anidulafungin, and 0.5–2 and 2.0 μg mL−1 for amphotericin B, respectively. The mating gene alleles of the clinical C. glabrata isolates were not associated with differences in the MICs of the tested antifungals, except for the MTL3 α‐allele and echinocandins.
Conclusions
The mating genotypes of the clinical C. glabrata isolates had no recognizable common effect on antifungal susceptibility.
This article is protected by copyright. All rights reserved.
Engin Kaplan Deniz Aktaş Şükran Önder Banu Metin Aylin Döğen Yasemin Oz Macit Ilkit
First published: 28 May 2019 https://doi.org/10.1111/myc.12945
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/myc.12945
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Abstract
Background
The sexual cycle of Candida glabrata is not known; however, genomic evidence is indicative of recombination among subpopulations and the genome harbors genes necessary for undergoing mating and meiosis, which may increase fitness. The relationship between specific mating type‐like (MTL) loci and antifungal susceptibility is not well understood in C. glabrata.
Objectives
We investigated different combinations of clinical C. glabrata isolate mating types and their antifungal susceptibility profiles.
Methods
Allele profiles of the mating genes of 103 clinical C. glabrata isolates were identified and their antifungal susceptibility to azoles, echinocandins, and amphotericin B was compared.
Results
The majority (88.3%) of screened isolates harboured the a allele in the locus. The MTL1, MTL2, and MTL3 loci harbored a (88.3%), a (95.1%), and α (71.8%) alleles, respectively. The C. glabrata isolates were susceptible to echinocandins but displayed high minimal inhibitory concentrations (MICs) for azoles. The MIC ranges and MIC90 values of all isolates were 1.0–≥64 and 8.0 μg mL−1 for fluconazole, 0.06–≥16.0 and 0.5 μg mL−1 for voriconazole, 0.06–≥16.0 and 1.0 μg mL−1 for posaconazole, ≤0.015–0.06, and 0.03 μg mL−1 for caspofungin, ≤0.015–0.06 and 0.015 μg mL−1 for anidulafungin, and 0.5–2 and 2.0 μg mL−1 for amphotericin B, respectively. The mating gene alleles of the clinical C. glabrata isolates were not associated with differences in the MICs of the tested antifungals, except for the MTL3 α‐allele and echinocandins.
Conclusions
The mating genotypes of the clinical C. glabrata isolates had no recognizable common effect on antifungal susceptibility.
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Biofilm formation by Candida auris isolated from colonizing sites and candidemia cases
Rachna Singh Mahaldeep Kaur Arunaloke Chakrabarti Shamanth A. Shankarnarayan Shivaprakash M. Rudramurthy
First published: 27 May 2019 https://doi.org/10.1111/myc.12947
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/myc.12947
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Abstract
Background
Candida auris, an emerging nosocomial pathogen, exhibits phenotypic variation. Non‐aggregating C. auris isolates display greater biofilm‐forming capacity and virulence than aggregate‐forming isolates. Most of the studies till date have focused on clinical isolates. The biofilm‐forming capacity of colonizing isolates remains uninvestigated.
Objectives
The present study aimed to elucidate the biofilm‐forming capacity of the colonizing isolates of C. auris, correlate it with their aggregation behavior and antifungal susceptibility, and compare it with that of the isolates from blood‐stream infection.
Methods
Colonizing and clinical (candidemia) isolates of C. auris were screened for aggregation behavior, biofilm‐forming capacity and antifungal susceptibility testing. Aggregation behavior was assessed microscopically. Biofilm‐forming capacity was determined on 96‐well flat‐bottomed microtiter plates. Antifungal susceptibility testing was performed by broth microdilution assay.
Results
Aggregative and non‐aggregative phenotypes were found to be predominantly associated with colonizing and clinical isolates respectively, with the former ones being stronger biofilm producers in the colonizing group. Non‐aggregative isolates in the colonizing group showed lower susceptibility to amphotericin B and fluconazole than aggregative isolates. In contrast, no association was noted between biofilm formation, aggregation behavior, and antifungal susceptibility amongst the clinical isolates.
Conclusion
Biofilm formation is a strain‐dependent trait in C. auris, strongly associated with the type and phenotypic behavior of the isolates. Colonizing isolates of this fungus were found to be predominantly aggregative in nature, with a higher biofilm‐forming capacity than non‐aggregative ones.
This article is protected by copyright. All rights reserved.
Rachna Singh Mahaldeep Kaur Arunaloke Chakrabarti Shamanth A. Shankarnarayan Shivaprakash M. Rudramurthy
First published: 27 May 2019 https://doi.org/10.1111/myc.12947
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/myc.12947
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Abstract
Background
Candida auris, an emerging nosocomial pathogen, exhibits phenotypic variation. Non‐aggregating C. auris isolates display greater biofilm‐forming capacity and virulence than aggregate‐forming isolates. Most of the studies till date have focused on clinical isolates. The biofilm‐forming capacity of colonizing isolates remains uninvestigated.
Objectives
The present study aimed to elucidate the biofilm‐forming capacity of the colonizing isolates of C. auris, correlate it with their aggregation behavior and antifungal susceptibility, and compare it with that of the isolates from blood‐stream infection.
Methods
Colonizing and clinical (candidemia) isolates of C. auris were screened for aggregation behavior, biofilm‐forming capacity and antifungal susceptibility testing. Aggregation behavior was assessed microscopically. Biofilm‐forming capacity was determined on 96‐well flat‐bottomed microtiter plates. Antifungal susceptibility testing was performed by broth microdilution assay.
Results
Aggregative and non‐aggregative phenotypes were found to be predominantly associated with colonizing and clinical isolates respectively, with the former ones being stronger biofilm producers in the colonizing group. Non‐aggregative isolates in the colonizing group showed lower susceptibility to amphotericin B and fluconazole than aggregative isolates. In contrast, no association was noted between biofilm formation, aggregation behavior, and antifungal susceptibility amongst the clinical isolates.
Conclusion
Biofilm formation is a strain‐dependent trait in C. auris, strongly associated with the type and phenotypic behavior of the isolates. Colonizing isolates of this fungus were found to be predominantly aggregative in nature, with a higher biofilm‐forming capacity than non‐aggregative ones.
This article is protected by copyright. All rights reserved.
Epidemiology and antifungal susceptibility patterns of Candida isolates from Greek women with vulvovaginal candidiasis
Sofia Maraki Viktoria Eirini Mavromanolaki Dimitra Stafylaki Eleni Nioti George Hamilos Anna Kasimati
First published: 27 May 2019 https://doi.org/10.1111/myc.12946
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/myc.12946
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Abstract
Background
Vulvovaginal candidiasis (VVC) is a common infection of the genital tract affecting millions of women worldwide. Data on epidemiological trends of VVC in Greece are scarce.
Objective
This study was undertaken to evaluate the prevalence of VVC among symptomatic women in Crete, Greece, identify the Candida species involved and determine their susceptibility to antifungals.
Patients/Methods
Over a six‐year period (2012‐2017), 10,256 symptomatic women with vaginitis were evaluated. Isolation of yeasts was performed on Sabouraud dextrose agar with chloramphenicol, and the isolates were identified using the API 20 C AUX and/or the Vitek 2 YST card. Susceptibility of the isolates to amphotericin, fluconazole, voriconazole and flucytosine, was determined by the Vitek 2 automated system. The results were interpreted according to Clinical and Laboratory Standards criteria.
Results
Vaginal swab cultures of 1,217 (11.9%) women yielded Candida species. Recurrent VVC was documented in 62 (5.1%) of them. C. albicans was the most frequently isolated species (75.6%), followed by C. glabrata (13.6%). Overall, resistance rates to amphotericin B, fluconazole, voriconazole, and flucytosine were 0.2%, 6.6%, 1.4%, and 2.1%, respectively. Fluconazole resistance of C. albicans significantly increased in the second period of the study (2015‐2017) (P=0.031).
Conclusion
This study demonstrated that VVC is a common infection among women in our region, with C. albicans being the predominant species involved. Although resistance to antifungals was infrequent, resistance to fluconazole among C. albicans isolates was found to significantly increase with time. Continued surveillance of changes in species distribution and susceptibility to antifungals are necessary to guide treatment.
This article is protected by copyright. All rights reserved.
Sofia Maraki Viktoria Eirini Mavromanolaki Dimitra Stafylaki Eleni Nioti George Hamilos Anna Kasimati
First published: 27 May 2019 https://doi.org/10.1111/myc.12946
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/myc.12946
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Abstract
Background
Vulvovaginal candidiasis (VVC) is a common infection of the genital tract affecting millions of women worldwide. Data on epidemiological trends of VVC in Greece are scarce.
Objective
This study was undertaken to evaluate the prevalence of VVC among symptomatic women in Crete, Greece, identify the Candida species involved and determine their susceptibility to antifungals.
Patients/Methods
Over a six‐year period (2012‐2017), 10,256 symptomatic women with vaginitis were evaluated. Isolation of yeasts was performed on Sabouraud dextrose agar with chloramphenicol, and the isolates were identified using the API 20 C AUX and/or the Vitek 2 YST card. Susceptibility of the isolates to amphotericin, fluconazole, voriconazole and flucytosine, was determined by the Vitek 2 automated system. The results were interpreted according to Clinical and Laboratory Standards criteria.
Results
Vaginal swab cultures of 1,217 (11.9%) women yielded Candida species. Recurrent VVC was documented in 62 (5.1%) of them. C. albicans was the most frequently isolated species (75.6%), followed by C. glabrata (13.6%). Overall, resistance rates to amphotericin B, fluconazole, voriconazole, and flucytosine were 0.2%, 6.6%, 1.4%, and 2.1%, respectively. Fluconazole resistance of C. albicans significantly increased in the second period of the study (2015‐2017) (P=0.031).
Conclusion
This study demonstrated that VVC is a common infection among women in our region, with C. albicans being the predominant species involved. Although resistance to antifungals was infrequent, resistance to fluconazole among C. albicans isolates was found to significantly increase with time. Continued surveillance of changes in species distribution and susceptibility to antifungals are necessary to guide treatment.
This article is protected by copyright. All rights reserved.
Dermatological manifestations of fungal infection in patients with febrile neutropaenia: A review of the literature
Austin J. Maddy Nelson Sanchez Bhavarth S. Shukla Andrea D. Maderal
First published: 09 May 2019 https://doi.org/10.1111/myc.12928
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Abstract
Febrile neutropaenia (FNP) is a common cause of morbidity and mortality in immunocompromised patients. Although most infections are caused by bacterial pathogens, fungal infections are becoming increasingly more common. Due to its rarity, the diagnosis of fungal infections in febrile neutropenic patients is often delayed. To provide current clinical features, epidemiology, aetiology, diagnosis and treatment of cutaneous involvement of fungal infection in patients with FNP. A retrospective literature review of PubMed was performed, with no language or publishing data restrictions, yielding 116 results. We queried each case for cutaneous lesions associated with fungal pathogens in FNP. We found 54 publications with 215 reported cases of cutaneous manifestations of fungal injury in patients with FNP. This study is limited in that it is a literature review of a disease that is likely underreported. Cutaneous lesions caused by yeasts such as Candida and Trichosporon manifest as diffuse erythematous papules and usually do not develop central necrosis or eschar, while moulds will present as tender nodules that subsequently develop eschar and necrosis. Recognising the cutaneous manifestations of fungal disease can assist in the diagnosis and management of these infections.
Austin J. Maddy Nelson Sanchez Bhavarth S. Shukla Andrea D. Maderal
First published: 09 May 2019 https://doi.org/10.1111/myc.12928
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Abstract
Febrile neutropaenia (FNP) is a common cause of morbidity and mortality in immunocompromised patients. Although most infections are caused by bacterial pathogens, fungal infections are becoming increasingly more common. Due to its rarity, the diagnosis of fungal infections in febrile neutropenic patients is often delayed. To provide current clinical features, epidemiology, aetiology, diagnosis and treatment of cutaneous involvement of fungal infection in patients with FNP. A retrospective literature review of PubMed was performed, with no language or publishing data restrictions, yielding 116 results. We queried each case for cutaneous lesions associated with fungal pathogens in FNP. We found 54 publications with 215 reported cases of cutaneous manifestations of fungal injury in patients with FNP. This study is limited in that it is a literature review of a disease that is likely underreported. Cutaneous lesions caused by yeasts such as Candida and Trichosporon manifest as diffuse erythematous papules and usually do not develop central necrosis or eschar, while moulds will present as tender nodules that subsequently develop eschar and necrosis. Recognising the cutaneous manifestations of fungal disease can assist in the diagnosis and management of these infections.
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480
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