Post covid cerebral phaeohyphomycosis by Rhinocladiella mackenziei: An unusual association.

Cerebral phaeohyphomycosis (CP) is a rare but a highly morbid fungal infection of the central nervous system caused by the fungi belonging to the order Chaetothyriales, which includes Cladophialophora bantiana, Exophiala dermatitidis, Rhinocladiella mackenziei (RM) etc. This disease is associated with poor clinical outcomes, with reported mortality of over 80%. We present the case of a 65-year gentleman who developed CP secondary to RM infection following COVID-19 and the associated challenges in his medical and surgical management.

[Fungal infection by Cladophialophora bantiana and development of cerebral phaeohyphomycosis. A systematic review of 58 case reports]. / Infección micótica por Cladophialophora bantiana y desarrollo de feohifomicosis cerebral. Revisión sistemática de 58 informes de caso.

INTRODUCTION: Cladophialophora bantiana is a filamentous fungus, known as a dematiaceous fungus because of the presence of melanin. This fungus is of clinical importance because it is neurotropic and causes cerebral phaeohyphomycosis. MATERIAL AND METHODS: The available scientific information on the development of cerebral phaeohyphomycosis caused by Cladophialophora bantiana was analysed by selecting articles from the PubMed, Scopus and Google Scholar databases that describe case reports of fungal infection by C. bantiana in adults, taking into account the analysis of the patients' symptomatology, clinical history and neuroanatomical damage, in addition to considering the mortality of the condition. RESULTS: India and United States were the countries with most case reports, with 32 and 11 cases respectively. Moreover, in terms of neuroanatomical lesions, the majority of patients suffered mixed lesions (29%) and frontal lobe lesions (22%). In accordance with the patients' condition, the pathology has a mortality rate of 62%. CONCLUSIONS: It is concluded that cerebral phaeohyphomycosis has a high mortality rate, there is no standardised treatment and, in most cases, the fungal infection of the brain is mixed and affects several different parts of it. Furthermore, if not diagnosed and treated in time, it can lead to the patients' death.

TITLE: Infección micótica por Cladophialophora bantiana y desarrollo de feohifomicosis cerebral. Revisión sistemática de 58 informes de caso.Introducción. Cladophialophora bantiana es un hongo filamentoso, denominado hongo dematiáceo por la presencia de melanina. Este hongo tiene importancia clínica por ser neurotrópico y causar feohifomicosis cerebral. Material y métodos. Se analizó la información científica disponible sobre el desarrollo de feohifomicosis cerebral provocada por Cladophialophora bantiana, seleccionando artículos de las bases de PubMed, Scopus y Google Scholar, que describen informes de caso sobre infección micótica de C. bantiana en adultos, considerando el análisis de la sintomatología, el historial clínico y los daños neuroanatómicos de los pacientes, además de considerar la mortalidad de la patología. Resultados. La India y Estados Unidos fueron los países con más informes de caso, 32 y 11 casos, respectivamente. Asimismo, en cuanto a las lesiones neuroanatómicas, en su mayoría, los pacientes sufrieron lesiones mixtas (29%) y del lóbulo frontal (22%). De acuerdo con el estado de los pacientes, la patología tiene una mortalidad del 62%. Conclusiones. Se concluye que la feohifomicosis cerebral tiene una alta mortalidad, no existe un tratamiento estandarizado y, en la mayoría de los casos, la infección fúngica del cerebro es mixta y afecta a varias partes del cerebro; además, si no se diagnostica y trata a tiempo, puede ocasionar la muerte de los pacientes.

Clinical characteristics of central nervous system phaeohyphomycosis: A brief report of 20 years' experience.

Central nervous system (CNS) phaeohyphomycosis is a rare and often fatal fungal infection. Our study reported a case series of eight CNS phaeohyphomycosis cases at our institution over the past 20 years. We did not observe the common pattern of risk factors, abscess location, or number of abscesses among them. Most patients were immunocompetent without classic risk factors for fungal infection. Early diagnosis and aggressive management with surgical intervention and prolonged antifungal therapy can lead to a favorable outcome. The study highlights the need for further research to better understand the pathogenesis and optimal management of this challenging rare infection.

Cerebral phaeohyphomycosis: The 'Dark Side' of fungal infections.

PURPOSE: Cerebral phaeohyphomycosis is a rare and fatal fungal infection of the central nervous system (CNS) caused by dematiaceous fungi. The aim of this study was to analyse the clinico- radiological presentation, pathology and outcome of cerebral phaeohyphomycosis and discuss the relevant literature. PATIENTS AND METHODS: Data of 7 patients diagnosed with cerebral phaeohyphomycosis and managed at our institute between 2014 and 2020 was collected and reviewed retrospectively. The diagnosis was established after surgery on KOH mount, Sabouraud dextrose agar, frozen section or histopathology. The clinical, radiological and pathological characteristics along with outcomes were analysed. RESULTS: Three patients with underlying comorbidities [chronic renal failure-2 and haematological malignancy -1] presented with brain abscess. The remaining 4 had no comorbidities. Two of them mimicked cystic glioma and one patient presented as intraventricular tumour. Another patient on anti- tubercular treatment for suspected pulmonary tuberculosis presented with encephalitis. Histopathology in all patients showed diffuse micro abscesses with coarse and reactive gliosis in the adjacent brain parenchyma and chronic lymphomononuclear inflammation without angioinvasion or vasculitis. Four showed granuloma formation. Antifungals were started after diagnosis. Six out of seven patients died and one was lost to follow up. CONCLUSION: Cerebral phaeohyphomycosis presents as abscesses in immunocompromised patients and mimics tumours in immunocompetent patients. KOH mount and frozen section examination is simple yet effective tool for establishing early diagnosis. Overall, the prognosis is dismal. Administering antifungals early in the course of management along with aggressive surgical excision may improve outcomes.

Morocco as a possible source for acquisition of Rhinocladiella mackenziei.

Rhinocladiella mackenziei cerebral phaeohyphomycosis is a rare severe disease that has been typically described in the Middle East. Here, we report 2 cases of R. mackenziei cerebral phaeohyphomycosis in patients from Morocco, diagnosed and treated in France, and raise a concern about the ever-going extension of the area at risk for this devastating invasive fungal infection.

Invasive cerebral phaeohyphomycosis in a Chinese boy with CARD9 deficiency and showing unique radiological features, managed with surgical excision and antifungal treatment.

We report this rare case of cerebral phaeohyphomycosis in a previously healthy Chinese boy, who was found to have caspase recruitment domain family member 9 (CARD9) deficiency. Initial radiological features suggested a neoplastic cerebral lesion, while histopathological examination supplemented by internal transcribed sequencing (ITS) of cerebral tissue confirmed the diagnosis of phaeohyphomycosis. He was treated with intravenous (IV) liposomal amphotericin B and voriconazole, guided by plasma and cerebrospinal fluid (CSF) level monitoring at drug initiation. At the 1 year follow-up, the patient demonstrated near complete neurological and radiological recovery.

Cerebral phaeohyphomycosis due to Cladophialophora bantiana in a French Guianese child.

We report a case of cerebral phaeohyphomycosis, a fungal brain infection due to a dark (dematiaceous) fungi in a 6-year-old French Guyanese boy. The child presented fever and drowsiness due to several paraventricular brain abscesses. Neurological surgeries were performed to reduce intracranial hypertension and to obtain abscess biopsies. Mycological cultures of intraoperative samples led to the diagnosis of cerebral phaeohyphomycosis due to Cladophialophora bantiana. The patient neurological status deteriorated and remained critical after several weeks of combination antifungal therapy with voriconazole 8mg/kg/day, liposomal amphotericin B 10mg/kg/day and flucytosine 200mg/kg/day. A complete surgical resection was not possible because of multiple small abscesses. A multidisciplinary ethical staff decided on home medical care with palliative ventriculoperitoneal shunt, nasogastric feeding and analgesics. One year later, the patient's neurological condition had improved and cerebral lesions had regressed, while he had not received any antifungal treatment but only traditional medicines. Cerebral phaeohyphomycosis are rare diseases affecting immunocompromised but also apparently non-immunocompromised patients, as in this case. A complete surgical resection is not always possible and mortality rates are high in spite of treatments with a combination of antifungals. The diagnosis may be difficult because of these dematiaceous fungi's slowly growing and their potential pathogenicity for laboratory staff.

Cerebral phaeohyphomycosis due to Rhinocladiella mackenziei in Persian Gulf region: A case and review.

Cerebral phaeohyphomycosis is frequently a fatal disease caused by truly neurotropic dematiaceous fungi. Although rare, this infection occurs especially among immunocompetent patients, and the clinical symptoms are often misdiagnosed as a cerebral tumour or bacterial brain abscess. The appropriate diagnosis and therapy of cerebral infections by melanized fungi are very challenging if they are caused by mysterious fungi with unknown ecological niche. We reported the second case of cerebral phaeohyphomycosis due to Rhinocladiella mackenziei in Iran and the first culture-confirmed case. In this report, the differential diagnosis and histopathological findings are discussed and a review of the literature is provided.

Genomic Analyses of Cladophialophora bantiana, a Major Cause of Cerebral Phaeohyphomycosis Provides Insight into Its Lifestyle, Virulence and Adaption in Host.

Cladophialophora bantiana is a dematiaceous fungus with a predilection for causing central nervous system (CNS) infection manifesting as brain abscess in both immunocompetent and immunocompromised patients. In this paper, we report comprehensive genomic analyses of C. bantiana isolated from the brain abscess of an immunocompetent man, the first reported case in Malaysia and Southeast Asia. The identity of the fungus was determined using combined morphological analysis and multilocus phylogeny. The draft genome sequence of a neurotrophic fungus, C. bantiana UM 956 was generated using Illumina sequencing technology to dissect its genetic fundamental and basic biology. The assembled 37.1 Mb genome encodes 12,155 putative coding genes, of which, 1.01% are predicted transposable elements. Its genomic features support its saprophytic lifestyle, renowned for its versatility in decomposing hemicellulose and pectin components. The C. bantiana UM 956 was also found to carry some important putative genes that engaged in pathogenicity, iron uptake and homeostasis as well as adaptation to various stresses to enable the organism to survive in hostile microenvironment. This wealth of resource will further catalyse more downstream functional studies to provide better understanding on how this fungus can be a successful and persistent pathogen in human.

A case of cerebral phaeohyphomycosis caused by Fonsecaea monophora, a neurotropic dematiaceous fungus, and a review of the literature.

The Fonsecaea species, which are the leading causes of chromoblastomycosis, are not considered neurotropic fungal agents. Fonsecaea pedrosoi is the primary species in the genus and is usually isolated from chromoblastomycosis cases. However, the recently distinguished species F. monophora has been reported in a few cerebral phaeohyphomycosis cases. Here, a case of cerebral phaeohyphomycosis caused by Fonsecaea monophora is presented in a 71-year-old female subject with chronic diabetes mellitus and hypertension. The identification of F. monophora was made through mycological and molecular analysis, and an isolate was differentiated from the closely related F. pedrosoi by sequence data on key bases on the ribosomal internal transcribed spacer region. The case was successfully treated with surgical and medical approaches, and the patient has remained healthy and stable after a ten-month follow up. Given the increasing incidence of this type of infection of the central nervous system (CNS), this case provides further support for the consideration that F. monophora might represent a neurotropic agent.

Disseminated Cladophialophora bantiana disease in a patient with prediabetes.

Cladophialophora bantiana, a dematiaceous fungus from the family Phaeohyphomycetes, is highly neurotropic and primarily reported as a rare cause of brain abscess. Pulmonary infection and disease outside the central nervous system is extremely rare, particularly in immunocompetent patients. We report an unusual case of disseminated cladosporiosis in a young man with a new diagnosis of prediabetes but no other identifiable risk factors for disease. Fungal cultures were positive for C. bantiana from brain abscess aspiration, vertebral bone cultures and subcarinal lymph node biopsy. Although the patient demonstrated initial good response to surgical debridement of brain abscesses plus antifungal therapy, he eventually expired from septic shock secondary to C. bantiana pneumonia and recurrent brain abscesses 2 years after initial diagnosis.

Cerebral phaeohyphomycosis--could early diagnosis have saved the patient?

Cladophialophora bantiana brain abscess is a rare and frequently fatal infection, often seen in immunocompetent individuals. 34 year old immunocompetent woman who presented with convulsions is reported. She was initially treated with antituberculous drug. During 15 days of treatment, she deteriorated. Hence she underwent craniotomy, which revealed brain abscesses due to C. bantiana. Subsequently she was treated with fluconazole , but eventually succumbed to the infection on the 7th day of treatment. Mortality remains high with this rare mycosis, even in immunocompetent patients. The case illustrates the clinical and radiological similarities between tuberculoma and other etiologies of brain abscesses. This emphasizes the need to perform histological and microbiological studies prior to the initiation of any form of therapy.

Feohifomicosis cerebral: descripción de un caso y revisión de la literatura / Cerebral phaeohyphomycosis: description of a case and review of the literature

La feohifomicosis cerebral es una micosis invasiva infrecuente, de mal pronóstico, sin tratamiento estandarizado y con muy pocos casos referenciados en la literatura. Entre los hongos responsables de la feohifomicosis se encuentra Cladophialophora bantiana, un hongo con especial tropismo por el sistema nervioso central. Se presenta un caso de absceso cerebral por C. bantiana en un adulto con enfermedad de Crohn y tratado con inmunosupresores. A pesar de la identificación del agente etiológico y del tratamiento quirúrgico y farmacológico administrado, el paciente evoluciona desfavorablemente y fallece 32 días después de la cirugía. La descripción del caso clínico se acompaña de una revisión de los episodios de feohifomicosis cerebral por C. bantiana publicados en los últimos 10 años. Los avances diagnósticos, incluyendo las nuevas técnicas de imagen, y el empleo de los nuevos antifúngicos no han mejorado el mal pronóstico de la feohifomicosis cerebral por C. bantiana, siendo aconsejable la combinación de tratamiento quirúrgico y farmacológico, aunque ninguna pauta terapéutica descrita en la literatura destaca por el éxito obtenido (AU)

Cerebral phaeohyphomycosis is a rare invasive fungal infection with very few cases referenced in the literature. There is no standardized treatment, and it is associated with poor outcomes. Cladophialophora bantiana, a fungus with special tropism for the central nervous system, is one of the causal agents of phaeohyphomycosis. The case presented here deals with a brain abscess by C. bantiana in an adult with Crohn's disease had beed being treated with immunosuppressive drugs. Despite the correct etiological diagnosis, surgical and pharmacological treatments, the patient died 32 days after surgery. A description of the case is followed by a review of all cerebral C. bantiana phaeohyphomycosis cases published in the last 10 years. Regardless of the use of advanced new imaging techniques in the diagnosis and treatment with new antifungal agents, cerebral phaeohyphomycosis by C. bantiana continues to have very poor prognosis. While new more successful therapeutic treatments appear, a combined surgical and pharmacological approach seems to be more appropriate for this severe mycosis (AU)

[Cladophilaphora bantiana brain abscess treated with voriconazole in an immunocompetent patient]. / Immün kompetan bir hastada vorikonazol ile tedavi edilen Cladophilaphora bantiana beyin apsesi.

Phaeohyphomycosis is a term used to define infections caused by darkly pigmented fungi with septate hyphae which contain melanin in their cell walls. Although fungi rarely cause central nervous system (CNS) infections, the incidence of CNS infections caused by melanin-containing fungi has been increasing in the recent years. Cladophialophora bantiana is the most frequently isolated species from cerebral phaeohyphomycosis. It mostly affects adult men in the second and third decade of life and about half of the cases occurs in immunocompetent patients. In this report, the isolation of C.bantiana from brain tissue of an immunocompetent patient who was operated with the initial diagnosis of a brain abscess, was presented. A 27 year-old male patient presenting without any chronic disease was admitted to the emergency department of our hospital with the complaints of persistent headache and diplopia. Magnetic resonance imaging (MRI) showed a space-occupying lesion in the right parietal lobe and left frontal lobe. Brain abscess was diagnosed in the patient who was referred to the neurosurgery department. Treatment was initiated with ceftriaxone and metronidazole. The abscess material sent for direct microscopic examination in the mycology laboratory was stained with Gram and Giemsa and cultured in the Sabouraud dextrose agar medium (SDA) with and without antibiotics (cycloheximide and chloramphenicol). Then, it was incubated at 37°C and 25°C. Direct examination and staining revealed a septate hyphae. The patient who received liposomal amphotericin B was referred to the infectious diseases department. Surface colors of all media including SDA with cycloheximide were olive-gray to black and contained velvety colonies. Lemon-like very long and integrated chains of conidium with poor branching in cornmeal Tween 80 agar, as well as growth at 42°C in passages, positive urease test result and cycloheximide resistance suggested C.bantiana. The isolate was confirmed as C. bantiana based on its DNA sequence analysis. Minimum inhibitor concentration (MIC) values for amphotericin B, voriconazole, caspofungin, and posaconazole were 2 µg/ml, 0.03 µg/ml, 0.03 µg/ml and 0.03 µg/ml, respectively. Liposomal amphotericin B was replaced with voriconazole due to the antifungal susceptibility profile. The patient who was symptom-free was discharged at 24 days after hospitalization with oral voriconazole treatment. In conclusion, cerebral phaeohyphomycosis should be considered in immunocompetent individuals. Given the fact that early diagnosis saves lives, such specimens should promptly be sent for mycological analysis.

[Cerebral phaeohyphomycosis: description of a case and review of the literature]. / Feohifomicosis cerebral: descripción de un caso y revisión de la literatura.

Cerebral phaeohyphomycosis is a rare invasive fungal infection with very few cases referenced in the literature. There is no standardized treatment, and it is associated with poor outcomes. Cladophialophora bantiana, a fungus with special tropism for the central nervous system, is one of the causal agents of phaeohyphomycosis. The case presented here deals with a brain abscess by C. bantiana in an adult with Crohn's disease had beed being treated with immunosuppressive drugs. Despite the correct etiological diagnosis, surgical and pharmacological treatments, the patient died 32 days after surgery. A description of the case is followed by a review of all cerebral C. bantiana phaeohyphomycosis cases published in the last 10 years. Regardless of the use of advanced new imaging techniques in the diagnosis and treatment with new antifungal agents, cerebral phaeohyphomycosis by C. bantiana continues to have very poor prognosis. While new more successful therapeutic treatments appear, a combined surgical and pharmacological approach seems to be more appropriate for this severe mycosis.