Bloodstream Infections Caused by Magnusiomyces capitatus and Magnusiomyces clavatus: Epidemiological, Clinical, and Microbiological Features of Two Emerging Yeast Species.

Magnusiomyces clavatus and Magnusiomyces capitatus are emerging yeasts with intrinsic resistance to many commonly used antifungal agents. Identification is difficult, and determination of susceptibility patterns with commercial and reference methods is equally challenging. For this reason, few data on invasive infections by Magnusiomyces spp. are available. Our objectives were to determine the epidemiology and susceptibility of Magnusiomyces isolates from bloodstream infections (BSI) isolated in Germany and Austria from 2001 to 2020. In seven institutions, a total of 34 Magnusiomyces BSI were identified. Identification was done by internal transcribed spacer (ITS) sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Antifungal susceptibility was determined by EUCAST broth microdilution and gradient tests. Of the 34 isolates, M. clavatus was more common (n = 24) than M. capitatus (n = 10). BSI by Magnusiomyces spp. were more common in men (62%) and mostly occurred in patients with hemato-oncological malignancies (79%). The highest in vitro antifungal activity against M. clavatus/M. capitatus was observed for voriconazole (MIC50, 0.03/0.125 mg/L), followed by posaconazole (MIC50, 0.125/0.25 mg/L). M. clavatus isolates showed overall lower MICs than M. capitatus. With the exception of amphotericin B, low essential agreement between gradient test and microdilution was recorded for all antifungals (0 to 70%). Both species showed distinct morphologic traits on ChromAgar Orientation medium and Columbia blood agar, which can be used for differentiation if no MALDI-TOF MS or molecular identification is available. In conclusion, most BSI were caused by M. clavatus. The lowest MICs were recorded for voriconazole. Gradient tests demonstrated unacceptably low agreement and should preferably not be used for susceptibility testing of Magnusiomyces spp.

Saprochaete clavata Outbreak Infecting Cancer Center through Dishwasher.

Saprochaete clavata is a pathogenic yeast responsible for rare outbreaks involving immunocompromised patients, especially those with hematologic malignancies. During February 2016-December 2017, we diagnosed S. clavata infections in 9 patients (8 with fungemia), including 3 within 1 month, at a cancer center in Marseille, France. The patients (median age 58 years), 4 of 9 of whom had acute myeloid leukemia, were hospitalized in 3 different wards. Ten environmental samples, including from 2 dishwashers and 4 pitchers, grew S. clavata, but no contaminated food was discovered. The outbreak ended after contaminated utensils and appliances were discarded. Whole-genome sequencing analysis demonstrated that all clinical and environmental isolates belonged to the same phylogenetic clade, which was unrelated to clades from previous S. clavata outbreaks in France. We identified a dishwasher with a deficient heating system as the vector of contamination.

Identification and antifungal susceptibility of Saprochaete clavata from invasive infections in Turkey.

Saprochaete clavata is an emerging opportunistic pathogen, that causes life-threatening infections, but there are limited evidence and information about the evaluation of in vitro antifungal susceptibility test results. The aim of this study was to determine S. clavata isolates from clinical specimens and to investigate their in vitro antifungal susceptibility. S. clavata was identified by API ID20C AUX (BioMérieux, Brussels, Belgium), MALDI TOF (Bruker Daltonik, Germany), and ITS gene region sequencing. In vitro susceptibility tests were performed using Sensititre YeastOne (TREK Diagnostic System, East Grinstead, UK). During the study period, 4,736 fungi were isolated from various clinical samples and, S. clavata was identified in eight patients with underlying diseases namely, pancreatic neoplasma, acute myeloid leukaemie, follicular lymphoma, cholelithiasis. Anidulafungin and micafungin minimum inhibitory concentration values were 1-2 and 1-4 mg/L, respectively, while those of the azole group antifungals were much lower. This is the first study in Turkey reporting isolation, identification and antifungal susceptibilities of S. clavata from clinical specimens. Higher MIC values seen in some isolates suggest that continuous monitoring of sensitivity rates and observation of regional differences will thus be useful guides in determining infection control and antifungal use policies.

Saprochaete clavata infections in patients undergoing treatment for haematological malignancies: A report of a monocentric outbreak and review of the literature.

Saprochaete clavata is a rare cause of fungaemia with deep organ involvement in patients with haematological malignancies with reported mortality rates of 60%-80%. We describe four cases of S clavata infection in a haematology unit over several months that were treated with voriconazole-based regimens. We also review the literature on factors that could contribute to earlier recognition and effective treatment of S clavata. We included all cases of culture-positive S clavata from sterile sites with associated signs of infection in patients undergoing treatment for a haematological malignancy. Isolates were identified by MALDI-TOF MS, and spectrum profiles were used to prepare clustering analysis of isolates. Susceptibility testing was performed using a commercial microtitre methods. Saprochaete clavata was isolated from the bloodstream in three cases and bronchial alveolar lavage (BAL) fluid in one case. Clustering analysis suggested strains of S clavata were clonal without evidence of divergence although a common source was not identified. Susceptibility testing yielded elevated MICs to fluconazole (8 mg/L) and echinocandins (>1-8 mg/L). All patients were treated with voriconazole-based regimens resulting in survival of 3/4 patients, who continued chemotherapy for their underlying malignancy without evidence of relapse. Saprochaete clavata is a rare but aggressive cause of breakthrough yeast infection in patients undergoing treatment for haematological malignancies, particularly patients with a prior history of echinocandin treatment. Timely initiation of appropriate treatment, aided by more rapid identification in microbiology laboratory, can reduce the risk of deep organ dissemination and patient death.

A rare case of purpuric rash caused by Saprochaete clavata in a pediatric patient with acute leukemia.

We present a 13-year-old boy who developed invasive infection with Saprochaete clavata after induction chemotherapy for B-cell acute lymphoblastic leukemia, complicated by fungemia, septic shock and acute renal, and liver failure. He developed purpuric papulonodules over bilateral upper and lower limbs, which also grew S clavata on fungal culture.

Saprochaete/Magnusiomyces: identification, virulence factors, and antifungal susceptibility of a challenging rare yeast.

Saprochaete/Magnusiomyces is among rare yeasts which might emerge as causes of breakthrough infections and nosocomial outbreaks. Identification to the species level might be a challenge in clinical laboratories. Data on virulence factors are scarce and antifungal susceptibility testing methodology is not definite. The aim of this study was to confirm species identification of clinical Saprochaete/Magnusiomyces isolates, find out their virulence factors, and obtain antifungal minimum inhibitory concentrations with two reference methods. Of the 57 isolates included, 54 were Saprochaete capitata and four were Saprochaete clavata as identified by ID32C, MALDI-TOF MS, and sequencing. When tested using phenotypic methods, all isolates were negative for coagulase, hemolysis, acid proteinase, and phospholipase, 56.1% were positive for esterase, and 19.3% had intermediate surface hydrophobicity. All isolates formed biofilms, with 40.4% of the isolates producing more biomass than biofilm-positive reference strain Candida albicans MYA-274. Antifungal susceptibility testing needed an adjusted spectrophotometric inoculum than recommended in reference methods for Candida/Cryptococcus. In conclusion, Saprochaete/Magnusiomyces species could be identified using methods available in the clinical laboratories. Despite the disadvantages of the phenotypic methods, esterase positivity was observed for the first time. A high biomass production was observed in biofilms. The need for standardization of antifungal susceptibility testing was brought to attention.

Septic shock due to co-infection with Legionella pneumophila and Saprochaete clavata.

Septic shock is the most dreaded presentation of an infection, carrying a reserved prognosis. Appropriate antimicrobial therapy is therefore the mainstay of treatment, alongside organ support as needed. Legionnaires' disease is mainly due to Legionella pneumophila serogroup 1 but it can be caused by other serogroups and species not detected by the urinary antigen test. Anti-tumour necrosis factor α therapy may increase the risk of invasive fungal infection, which carry a poor prognosis. We present a challenging case of a septic shock due to Legionella pneumophila and Saprochaete clavata infections, with a review of the two infections presented.

Saprochaete clavata Infection in Immunosuppressed Patients: Systematic Review of Cases and Report of the First Oral Manifestation, Focusing on Differential Diagnosis.

Background: Saprochaete clavata infection is an emerging issue in immunosuppressed patients, causing fulminant fungaemia. The purpose of this systematic review of cases is to retrieve all cases of S. clavata infection and describe oral lesions as the first manifestation of S. clavata infection. Methods: We report the first case of intraoral S. clavata infection in Acute Myeloid Leukemia (AML) affected subject, presenting as multiple grayish rapidly growing ulcerated swellings, and provide a review of all published cases of infection caused by S. clavata, according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, conducted by searching SCOPUS, Medline, and CENTRAL databases. Only articles in English were considered. Individual patient data were analyzed to identify risk factors for S. clavata infection. Results: Seventeen of 68 retrieved articles were included in the review reporting data on 96 patients (mean age 51.8 years, 57 males and 38 females). Most cases were disseminated (86) with a 60.2% mortality rate. Ninety-five were hematological patients, with AML being the most common (57 cases). Conclusions:S. clavata infection in immunosuppressed patients has a poor prognosis: middle-age patients, male gender and Acute Myeloid Leukemia should be considered risk factors. In immunosuppressed patients, the clinical presentation can be particularly unusual, imposing difficult differential diagnosis, as in the reported case.

Saprochaete clavata (Geotrichum clavatum) septicemia in a patient with multiple myeloma; An emerging case from Southeastern Turkey.

BACKGROUND AND PURPOSE: Invasive fungal infections (IFI) are life-threatening and can be seen in immuno-compromised patients with malignancy, those who undergo chemotherapy, or transplant recipients. The Candida and Aspergillus species are the most common IFI agents; however, infections can also be caused by rare fungal species. This case report is about a bloodstream infection due to Saprochaete clavata (formerly known as Geotrichum clavatum) in a woman with multiple myeloma. CASE REPORT: A 59-years-old woman suffered from fever, widespread rashes, and diarrhea after an autologous bone marrow transplantation. Peripheral blood cultures were taken from the patient and sent to the microbiology laboratory. Cultures grew white to cream-colored cottony colonies. Moreover, septate and branched hyphae and arthroconidia were seen under a microscope by lactophenol blue staining. The fungi colonies were identified by Maldi Biotyper 3. 1. (manufactured by Bruker Daltonics, USA) as S. clavata (G. clavatum) with a reliable score. Antifungal susceptibility test was carried out by the concentration gradient strip Etest method. Minimal inhibitory concentrations of Amphotericin B, fluconazole, voriconazole, posaconazole, and anidulafungin were determined as 4, 3, 0.125, 0.125, and > 32 mg/dL, respectively. Despite amphotericin B treatment, the patient died three days after the identification of the fungi. CONCLUSION: The IFIs are serious conditions that have high mortality rates. In the current case report, we aimed to draw attention to S. clavata which is a rare fungal agent.

Invasive Saprochaete Infections: An Emerging Threat to Immunocompromised Patients.

Saprochaete clavata and Saprochaete capitata are emerging fungal pathogens that are responsible for life threatening infections in immunocompromised patients, particularly in the setting of profound neutropenia. They have been associated with multiple hospital outbreaks mainly in Europe. In this article, we present a comprehensive review of the epidemiology, clinical presentation, diagnosis, antifungal susceptibility and treatment of these organisms. The diagnosis of invasive Saprochaete disease is challenging and relies primarily on the isolation of the fungi from blood or tissue samples. Both species are frequently misidentified as they are identical macroscopically and microscopically. Internal transcribed spacer sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry are useful tools for the differentiation of these fungi to a species level. Saprochaete spp. are intrinsically resistant to echinocandins and highly resistant to fluconazole. Current literature suggests the use of an amphotericin B formulation with or without flucytosine for the initial treatment of these infections. Treatment with extended spectrum azoles might be promising based on in vitro minimum inhibitory concentration values and results from case reports and case series. Source control and recovery of the immune system are crucial for successful therapy.

Healthcare-associated fungal outbreaks: New and uncommon species, New molecular tools for investigation and prevention.

Outbreaks of healthcare-associated fungal infections have repeatedly been described over recent years, often caused by new or uncommon species. Candida auris, a recently described multidrug-resistant yeast species, is certainly the most worrisome species having caused several severe healthcare outbreaks of invasive infections, on four continents. Also, large nosocomial outbreaks due to uncommon fungal species such as Exserohilum rostratum and Sarocladium kiliense, were both linked to contamination of medical products, however the source of another outbreak, caused by Saprochaete clavata, remains unresolved. Furthermore, these outbreaks identified new populations under threat in addition to those commonly at risk for invasive fungal infections, such as immunosuppressed and intensive care unit patients. All of these outbreaks have highlighted the usefulness of a high level of awareness, rapid diagnostic methods, and new molecular typing tools such as Whole Genome Sequencing (WGS), prompt investigation and aggressive interventions, including notification of public health agencies. This review summarizes the epidemiological and clinical data of the majority of healthcare-associated outbreaks reported over the last 6 years caused by uncommon or new fungal pathogens, as well as the contribution of WGS as support to investigate the source of infection and the most frequent control measures used.

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.

We report a case of a 27-year old man with severe aplastic anemia who developed a Saprochaete clavata (Geotrichum clavatum) disseminated invasive infection shortly prior a scheduled allogeneic bone marrow transplantation. Treatment with a combination of voriconazole, liposomal amphotericin B and adjuvant granulocyte transfusions was successful before neutrophil recovery.