Saprochaete clavata invasive infection: characterization, antifungal susceptibility, and biofilm evaluation of a rare yeast isolated in Brazil

ABSTRACT Rare emerging pathogens such as Saprochaete clavata are associated with invasive fungal diseases, high morbidity, mortality, rapidly fatal infections, and outbreaks. However, little is known about S. clavata infections, epidemiology, risk factors, treatment, biofilms, and disease outcomes. The objective of this study was to describe a new case of severe S. clavata infection in a patient diagnosed at a referral children’s hospital in Brazil, including antifungal minimal inhibitory concentration, S. clavata biofilm characterization, and molecular characterization. The S. clavata isolated from an immunocompromised 11-year-old male patient was characterized using MALDI-TOF, Gram staining, scanning electron microscopy (SEM), and next generation sequencing (NGS) of genomic DNA. Biofilm production was also evaluated in parallel with determining minimal inhibitory concentration (MIC) and biofilm sensitivity to antifungal treatment. We observed small to medium, whitish, farinose, dry, filamentous margin colonies, yeast-like cells with bacillary features, and biofilm formation. The MALDI-TOF system yielded a score of ≥ 2,000, while NGS confirmed S. clavata presence at the nucleotide level. The MIC values (in mg L-1) for tested drugs were as follows: fluconazole = 2, voriconazole ≤ 2, caspofungin ≥ 8, micafungin = 2, amphotericin B = 4, flucytosine ≤ 1, and anidulafungin = 1. Amphotericin B can be active against S. clavata biofilm and the fungus can be susceptible to new azoles. These findings were helpful for understanding the development of novel treatments for S. clavata-induced disease, including combined therapy for biofilm-associated infections.

[1]  J. Perfect,et al.  Global guideline for the diagnosis and management of rare yeast infections: an initiative of the ECMM in cooperation with ISHAM and ASM. , 2021, The Lancet. Infectious diseases.

[2]  P. Ortega,et al.  Eradication of Candida albicans Biofilm Viability: In Vitro Combination Therapy of Cationic Carbosilane Dendrons Derived from 4-Phenylbutyric Acid with AgNO3 and EDTA , 2021, Journal of fungi.

[3]  F. Dromer,et al.  Azole Susceptibility Profiles of More than 9,000 Clinical Yeast Isolates Belonging to 40 Common and Rare Species , 2021, Antimicrobial Agents and Chemotherapy.

[4]  Thomas M. Keane,et al.  Twelve years of SAMtools and BCFtools , 2020, GigaScience.

[5]  K. Popat,et al.  Crystallinity of TiO2 nanotubes and its effects on fibroblast viability, adhesion, and proliferation , 2020, Journal of Materials Science: Materials in Medicine.

[6]  D. Seidel,et al.  Saprochaete clavata Invasive Infections – A New Threat to Hematological-Oncological Patients , 2019, Front. Microbiol..

[7]  S. Knøchel,et al.  Microbial biofilm communities on Reverse Osmosis membranes in whey water processing before and after cleaning , 2019, Journal of Membrane Science.

[8]  V. Vullo,et al.  Disseminated fungal infection due to Saprochaete clavata in a kidney transplant recipient. , 2019, Journal de mycologie medicale.

[9]  L. N. Botello,et al.  Disseminated fungemia by Saprochaete clavata , 2019, Enfermedades infecciosas y microbiologia clinica (English ed.).

[10]  Wei Zhou,et al.  Invasive Fungal Infection Caused by Geotrichum clavatum in a Child with Acute Leukemia: First Documented Case from Mainland China. , 2019, Japanese journal of infectious diseases.

[11]  I. Salgüero Fernández,et al.  Disseminated fungemia by Saprochaete clavata. , 2019, Enfermedades infecciosas y microbiologia clinica.

[12]  A. Tortorano,et al.  Yeast-like filamentous fungi: Molecular identification and in vitro susceptibility study. , 2018, Medical mycology.

[13]  C. F. Rodrigues,et al.  Combination of Posaconazole and Amphotericin B in the Treatment of Candida glabrata Biofilms , 2018, Microorganisms.

[14]  J. Zahar,et al.  Healthcare-associated fungal outbreaks: New and uncommon species, New molecular tools for investigation and prevention , 2018, Antimicrobial Resistance & Infection Control.

[15]  J. Meis,et al.  Molecular Diagnostics of Arthroconidial Yeasts, Frequent Pulmonary Opportunists , 2017, Journal of Clinical Microbiology.

[16]  D. Seidel,et al.  Invasive infections due to Saprochaete and Geotrichum species: Report of 23 cases from the FungiScope Registry , 2017, Mycoses.

[17]  F. Rossi,et al.  Rapid identification of moulds and arthroconidial yeasts from positive blood cultures by MALDI-TOF mass spectrometry. , 2016, Medical mycology.

[18]  L. Pagano,et al.  A cluster of Geotrichum clavatum (Saprochaete clavata) infection in haematological patients: a first Italian report and review of literature , 2016, Mycoses.

[19]  N. Milpied,et al.  Saprochaete clavata invasive infection in a patient with severe aplastic anemia: Efficacy of voriconazole and liposomal amphotericin B with adjuvant granulocyte transfusions before neutrophil recovery following allogeneic bone marrow transplantation , 2016, Medical mycology case reports.

[20]  N. Gunde-Cimerman,et al.  Dishwashers provide a selective extreme environment for human-opportunistic yeast-like fungi , 2015, Fungal Diversity.

[21]  F. Jardin,et al.  Multicenter Outbreak of Infections by Saprochaete clavata, an Unrecognized Opportunistic Fungal Pathogen , 2014, mBio.

[22]  C. Récher,et al.  Concomitant cases of disseminated Geotrichum clavatum infections in patients with acute myeloid leukemia , 2014, Leukemia & lymphoma.

[23]  F. Jardin,et al.  Invasive Geotrichum clavatum Fungal Infection in an Acute Myeloid Leukaemia Patient: A Case Report and Review , 2014, Mycopathologia.

[24]  J. Meis,et al.  ESCMID and ECMM joint clinical guidelines for the diagnosis and management of rare invasive yeast infections. , 2014, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[25]  Björn Usadel,et al.  Trimmomatic: a flexible trimmer for Illumina sequence data , 2014, Bioinform..

[26]  D. Horn,et al.  The PATH (Prospective Antifungal Therapy) Alliance® registry and invasive fungal infections: update 2012. , 2012, Diagnostic microbiology and infectious disease.

[27]  Jun F. Liang,et al.  Susceptibility of Staphylococcus aureus biofilms to reactive discharge gases , 2011, Biofouling.

[28]  B. Arthington-Skaggs,et al.  Biofilm production and evaluation of antifungal susceptibility amongst clinical Candida spp. isolates, including strains of the Candida parapsilosis complex. , 2011, Medical mycology.

[29]  G. D. Hoog,et al.  Galactomyces Redhead & Malloch (1977) , 2011 .

[30]  Clinical,et al.  Reference method for broth dilution antifungal susceptibility testing of yeasts : Approved standard , 2008 .

[31]  K. Seifert,et al.  The yeasts, a taxonomic study , 2007, Antonie van Leeuwenhoek.

[32]  G. S. Hoog Ribosomal gene phylogeny and species delimitation in Geotrichum and its teleomorphs , 2004 .