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Infection Aug 2018Fungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the immune status of the host and the virulence of the fungal strain. Infections with fungi cause a significant morbidity in immunocompromised hosts, and the involvement of the CNS may lead to fatal consequences.
METHODS
One hundred and thirty-five articles on fungal neuroinfection in PubMed, Google Scholar, and Cochrane databases were selected for review using the following search words: "fungi and CNS mycoses", CNS fungal infections", "fungal brain infections", " fungal cerebritis", fungal meningitis", "diagnostics of fungal infections", and "treatment of CNS fungal infections". All were published in English with the majority in the period 2000-2018. This review focuses on the current knowledge of the epidemiology, clinical presentations, diagnosis, and treatment of selected FIs-CNS.
RESULTS
The FIs-CNS can have various clinical presentations, mainly meningitis, encephalitis, hydrocephalus, cerebral abscesses, and stroke syndromes. The etiologic factors of neuroinfections are yeasts (Cryptococcus neoformans, Candida spp., Trichosporon spp.), moniliaceous moulds (Aspergillus spp., Fusarium spp.), Mucoromycetes (Mucor spp., Rhizopus spp.), dimorphic fungi (Blastomyces dermatitidis, Coccidioides spp., Histoplasma capsulatum), and dematiaceous fungi (Cladophialophora bantiana, Exophiala dermatitidis). Their common route of transmission is inhalation or inoculation from trauma or surgery, with subsequent hematogenous or contiguous spread. As the manifestations of FIs-CNS are often non-specific, their diagnosis is very difficult. A fast identification of the etiological factor of neuroinfection and the application of appropriate therapy are crucial in preventing an often fatal outcome. The choice of effective drug depends on its extent of CNS penetration and spectrum of activity. Pharmaceutical formulations of amphotericin B (AmB) (among others, deoxycholate-AmBd and liposomal L-AmB) have relatively limited distribution in the cerebrospinal fluid (CSF); however, their detectable therapeutic concentrations in the CNS makes them recommended drugs for the treatment of cryptococcal meningoencephalitis (AmBd with flucytosine) and CNS candidiasis (L-AmB) and mucormycosis (L-AmB). Voriconazole, a moderately lipophilic molecule with good CNS penetration, is recommended in the first-line therapy of CNS aspergillosis. Other triazoles, such as posaconazole and itraconazole, with negligible concentrations in the CSF are not considered effective drugs for therapy of CNS fungal neuroinfections. In contrast, clinical data have shown that a novel triazole, isavuconazole, achieved considerable efficacy for the treatment of some fungal neuroinfections. Echinocandins with relatively low or undetectable concentrations in the CSF do not play meaningful role in the treatment of FIs-CNS.
CONCLUSION
Although the number of fungal species causing CNS mycosis is increasing, only some possess well-defined treatment standards (e.g., cryptococcal meningitis and CNS aspergillosis). The early diagnosis of fungal infection, accompanied by identification of the etiological factor, is needed to allow the selection of effective therapy in patients with FIs-CNS and limit their high mortality.
Topics: Blood-Brain Barrier; Central Nervous System Fungal Infections; Disease Management; Fungi; Host-Pathogen Interactions; Humans; Risk Factors; Virulence
PubMed: 29785613
DOI: 10.1007/s15010-018-1152-2 -
World Journal of Clinical Cases Sep 2021is a genus comprising several species of opportunistic black yeasts, which belongs to Ascomycotina. It is a rare cause of fungal infections. However, infections are...
is a genus comprising several species of opportunistic black yeasts, which belongs to Ascomycotina. It is a rare cause of fungal infections. However, infections are often chronic and recalcitrant, and while the number of cases is steadily increasing in both immunocompromised and immunocompetent people, detailed knowledge remains scarce regarding infection mechanisms, virulence factors, specific predisposing factors, risk factors, and host response. The most common manifestations of infection are skin infections, and the most frequent type of deep infection is pulmonary infection due to inhalation. The invasive disease ranges from cutaneous or subcutaneous infection to systemic dissemination to internal organs. The final identification of the causative organism should be achieved through a combination of several methods, including the newly introduced diagnostic analysis, matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry, together with sequencing of the ribosomal ribonucleic acid internal transcribed spacer region of the fungi, and histological and culture findings. Regarding treatment, because anti-infective agents and natural compounds exhibited poor antibiofilm activity, few treatments have ultimately been found to be effective for specific antifungal therapy, so the optimal antifungal therapy and duration of therapy for these infections remain unknown. Therefore, most forms of disease caused by require aggressive combination therapies: Both surgical intervention and aggressive antifungal therapy with novel compounds and azoles are necessary for effective treatment.
PubMed: 34621853
DOI: 10.12998/wjcc.v9.i27.7963 -
American Journal of Ophthalmology Case... Sep 2020To report a case of endogenous endophthalmitis.
PURPOSE
To report a case of endogenous endophthalmitis.
OBSERVATIONS
An immunosuppressed patient with a history of hairy cell leukemia undergoing chemotherapy presents with rapidly progressing panophthalmitis. The patient was treated medically without improvement and underwent a pars plana vitrectomy which showed multiple retinal abscesses. Vitreous fluid cultures grew a rare fungal organism, .
CONCLUSIONS AND IMPORTANCE
This is the first reported case of causing endogenous endophthalmitis. Rare fungal organisms can present with rapid progression to panophthalmitis in immunocompromised hosts.
PubMed: 32637729
DOI: 10.1016/j.ajoc.2020.100774 -
Virulence Dec 2019The black yeast is an opportunistic pathogen, causing phaeohyphomycosis in immunosuppressed patients, chromoblastomycosis and fatal infections of the central nervous... (Review)
Review
The black yeast is an opportunistic pathogen, causing phaeohyphomycosis in immunosuppressed patients, chromoblastomycosis and fatal infections of the central nervous system in otherwise healthy Asian patients. In addition, it is also regularly isolated from respiratory samples from cystic fibrosis patients, with rates varying between 1% and 19%.Melanin, as part of the cell wall of black yeasts, is one major factor known contributing to the pathogenicity of and increased resistance against host defense and anti-infective therapeutics. Further virulence factors, e.g. the capability to adhere to surfaces and to form biofilm were reported. A better understanding of the pathogenicity of is essential for the development of novel preventive and therapeutic strategies. In this review, the current knowledge of prevalence, clinical importance, diagnosis, microbiological characteristics, virulence attributes, susceptibility, and resistances as well as therapeutically strategies are discussed.
Topics: Animals; Biofilms; Cystic Fibrosis; Exophiala; Humans; Immunocompromised Host; Melanins; Mice; Opportunistic Infections; Phaeohyphomycosis; Prevalence; Virulence
PubMed: 30887863
DOI: 10.1080/21505594.2019.1596504 -
Mycopathologia Jun 2018We report a case of a 59-year-old male patient with a postoperative fungal infection of the left eye. A dark-pigmented yeast, Exophiala dermatitidis (previously known as... (Review)
Review
We report a case of a 59-year-old male patient with a postoperative fungal infection of the left eye. A dark-pigmented yeast, Exophiala dermatitidis (previously known as Wangiella dermatitidis), was identified from the culture of the biopsy taken from the posterior capsule. The infection was successfully eradicated by a combination of surgical and medical (i.e., voriconazole and fluconazole) treatment. This is the first report of successfully treated E. dermatitidis endophthalmitis, which demonstrates that a prompt and aggressive antifungal therapy combined with surgical intervention is necessary to prevent vision loss in cases of endophthalmitis due to Exophiala species. Beside the case description, we also aim to provide a literature review of previously reported eye infections caused by Exophiala species in order to help the future diagnosis and management of the disease.
Topics: Antifungal Agents; Biopsy; Debridement; Endophthalmitis; Exophiala; Humans; Male; Microbiological Techniques; Middle Aged; Phaeohyphomycosis; Pigments, Biological; Surgical Wound Infection; Treatment Outcome
PubMed: 29374798
DOI: 10.1007/s11046-017-0235-4 -
Computational and Structural... 2021Melanized fungi have been isolated from some of the harshest radioactive environments, and their ability to thrive in these locations is in part due to the pigment...
Melanized fungi have been isolated from some of the harshest radioactive environments, and their ability to thrive in these locations is in part due to the pigment melanin. Melanin imparts a selective advantage to fungi by providing a physical shield, a chemical shield, and possibly a signaling mechanism. In previous work we demonstrated that protracted exposure of the melanized yeast to mixed alpha-, beta-, and gamma-emitting radiation resulted in an adapted strain able to mount a unique response to ionizing radiation in the environment in a melanin-dependent fashion. By exploring the genome and transcriptome of this adapted melanized strain relative to a non-irradiated control we determined the altered response was transcriptomic in nature, as whole genome sequencing revealed limited variation. Transcriptomic analysis indicated that of the adapted isolates analyzed, two lineages existed: one like the naïve, non-adapted strain, and one with a unique transcriptomic signature that exhibited downregulation of metabolic processes, and upregulation of translation-associated genes. Analysis of differential gene expression in the adapted strain showed an overlap in response between the control conditions and reactive oxygen species conditions, whereas exposure to an alpha particle source resulted in a robust downregulation of metabolic processes and upregulation of DNA replication and repair genes, and RNA metabolic processes. This suggest previous exposure to radiation primes the fungus to respond to subsequent exposures in a unique way. By exploring this unique response, we have expanded our knowledge of how melanized fungi interact with and respond to ionizing radiation in their environment.
PubMed: 33425251
DOI: 10.1016/j.csbj.2020.12.013 -
Cells Apr 2020The neurotropic and extremophilic black yeast () inhabits diverse indoor environments, in particular bathrooms, steam baths, and dishwashers. Here, we show that the...
The neurotropic and extremophilic black yeast () inhabits diverse indoor environments, in particular bathrooms, steam baths, and dishwashers. Here, we show that the selected strain, EXF-10123, is polymorphic, can grow at 37 °C, is able to assimilate aromatic hydrocarbons (toluene, mineral oil, n-hexadecane), and shows abundant growth with selected neurotransmitters (acetylcholine, gamma-aminobutyric acid, glycine, glutamate, and dopamine) as sole carbon sources. We have for the first time demonstrated the effect of on neuroblastoma cell model SH-SY5Y. Aqueous and organic extracts of biomass reduced SH-SY5Y viability by 51% and 37%, respectively. Melanized extracellular vesicles (EVs) prepared from this strain reduced viability of the SH-SY5Y to 21%, while non-melanized EVs were considerably less neurotoxic (79% viability). We also demonstrated direct interactions of with SH-SY5Y by scanning electron and confocal fluorescence microscopy. The observed invasion and penetration of neuroblastoma cells by hyphae presumably causes the degradation of most neuroblastoma cells in only three days. This may represent a so far unknown indirect or direct cause for the development of some neurodegenerative diseases such as Alzheimer's.
Topics: Cell Death; Exophiala; Humans; Neuroblastoma
PubMed: 32295162
DOI: 10.3390/cells9040963 -
Antimicrobial Agents and Chemotherapy Dec 2017interactions of tacrolimus, a calcineurin inhibitor, and azoles, including itraconazole, voriconazole, and posaconazole, against planktonic cells and biofilms of were...
interactions of tacrolimus, a calcineurin inhibitor, and azoles, including itraconazole, voriconazole, and posaconazole, against planktonic cells and biofilms of were assessed via a broth microdilution checkerboard technique. A total of 16 clinical isolates were studied. The results revealed favorable synergistic inhibitory activity between tacrolimus and itraconazole, voriconazole, or posaconazole against 68.8%, 87.5%, and 100% of tested strains of planktonic , respectively.However, limited synergism was observed against biofilms of No antagonism was observed in all combinations.
Topics: Antifungal Agents; Biofilms; Calcineurin Inhibitors; Candida parapsilosis; Drug Synergism; Exophiala; Humans; Itraconazole; Microbial Sensitivity Tests; Phaeohyphomycosis; Tacrolimus; Triazoles; Voriconazole
PubMed: 28923863
DOI: 10.1128/AAC.00948-17 -
Antimicrobial Agents and Chemotherapy Mar 2022Limited data are available on breakthrough fungemia, defined as fungemia that develops on administration of antifungal agents, in patients with hematological disorders....
Limited data are available on breakthrough fungemia, defined as fungemia that develops on administration of antifungal agents, in patients with hematological disorders. We reviewed the medical and microbiological records of adult patients with hematological diseases who had breakthrough fungemia between January 2008 and July 2019 at Toranomon Hospital and Toranomon Hospital Kajigaya in Japan. A total of 121 cases of breakthrough fungemia were identified. Of the 121 involved patients, 83, 11, 5, and 22 were receiving micafungin, voriconazole, itraconazole, and liposomal amphotericin B, respectively, when the breakthrough occurred. Of the 121 causative breakthrough fungal strains, 96 were species, and the rest were 13 cases of species, 7 of Fusarium species, 2 of Rhodotorula mucilaginosa, and 1 each of Cryptococcus neoformans, Exophiala dermatitidis, and Magnusiomyces capitatus. The crude 14-day mortality rate of breakthrough fungemia was 36%. Significant independent factors associated with the crude 14-day mortality rate were age of ≥60 years (0.011), chronic renal failure (0.0087), septic shock (0.0001), steroid administration (0.0085), and liposomal amphotericin B breakthrough fungemia (0.0011). An absolute neutrophil count of >500/μL was significantly more common in candidemia in the multivariate analysis ( = 0.0065), neutropenia and nonallogeneic hematopoietic stem cell transplants were significantly more common in fungemia (0.036 and 0.033, respectively), and voriconazole breakthrough fungemia and neutropenia were significantly more common in Fusarium fungemia (0.016 and 0.016, respectively). The epidemiological and clinical characteristics of breakthrough fungemia of patients with hematological disorders were demonstrated. Some useful factors to predict candidemia, fungemia, and Fusarium fungemia were identified.
Topics: Adult; Antifungal Agents; Candida; Candidemia; Cryptococcus neoformans; Fungemia; Fusarium; Hematologic Diseases; Humans; Middle Aged; Trichosporon
PubMed: 35041512
DOI: 10.1128/AAC.02081-21 -
Medical Mycology Oct 2020An increased prevalence of various filamentous fungi in sputum samples of patients with cystic fibrosis (CF) has been reported. The clinical significance, however, is...
An increased prevalence of various filamentous fungi in sputum samples of patients with cystic fibrosis (CF) has been reported. The clinical significance, however, is mostly unclear. The aim of this study was to investigate the clinical relevance of Scedosporium spp. and Exophiala dermatitidis from sputum samples of patients with CF in the Netherlands. In this cross-sectional study, all CF patients of the Dutch national CF registry who were treated at five of the seven recognized CF centers during a 3-year period were included. We linked clinical data of the national CF registry with the national Dutch filamentous fungal database. We investigated the association between clinical characteristics and a positive sputum sample for Scedosporium spp. and E. dermatitidis, using logistic regression. Positive cultures for fungi were obtained from 3787 sputum samples from 699 of the 1312 patients with CF. Scedosporium spp. was associated with severe genotype, CF-related diabetes, several microorganisms, and inhaled antibiotics. E. dermatitidis was associated with older age, female sex, and Aspergillus spp. CF patients with and without Scedosporium spp. or E. dermatitidis seemed comparable in body mass index and lung function. This study suggests that Scedosporium spp. and E. dermatitidis are probably no major pathogens in CF patients in the Netherlands. Greater understanding of epidemiologic trends, risk factors, and pathogenicity of filamentous fungi in the respiratory tracts of patients with CF is needed.
Topics: Adolescent; Adult; Child; Cross-Sectional Studies; Cystic Fibrosis; Exophiala; Female; Humans; Invasive Fungal Infections; Male; Netherlands; Phaeohyphomycosis; Prevalence; Scedosporium; Sputum; Young Adult
PubMed: 32030418
DOI: 10.1093/mmy/myaa003