Primary cerebral phaeohyphomycosis is a life-threatening disease caused by neurotropic dematiaceous fungi. At present, there are no consensus guidelines regarding optimal antifungal therapy in such cases. Generally, a combination of antifungal agents is recommended for treatment. However, the activities of antifungal combinations against these fungi have not been investigated. In this study, we evaluated the in vitro activities of 13 double and five triple antifungal combinations against clinical isolates of Cladophialophora bantiana (n = 7), Fonsecaea monophora (n = 2), and Cladosporium cladosporioides (n = 1), using a simplified checkerboard procedure. The minimum inhibitory concentrations (MICs) of nine antifungal drugs were determined by the broth microdilution method, and the interaction between antifungal agents in each combination was assessed by the fractional inhibitory concentration index. Excellent activity was observed for posaconazole and itraconazole. Flucytosine had potent activity against C. bantiana but was ineffective against F. monophora, and C. cladosporioides. The echinocandins demonstrated high MICs for all the isolates. Synergistic interactions were observed for all the double combinations, except when itraconazole was combined with either amphotericin B or flucytosine. The combination of amphotericin B with caspofungin showed synergistic interactions against 40% of the isolates. Antagonism was observed with isavuconazole-flucytosine combination against two C. bantiana isolates. The triple combinations of caspofungin and flucytosine with amphotericin B or posaconazole were synergistic against one isolate of F. monophora. For C. cladosporioides, synergy was observed for the triple combination of amphotericin B with caspofungin and flucytosine. Our results indicate that combination of caspofungin with amphotericin B or a triazole, with or without 5-flucytosine has great potential against neurotropic dematiaceous fungi.IMPORTANCEThis research uses a modified version of the checkerboard assay to standardize the in vitro testing of double and triple combinations of antifungal agents against neurotropic dematiaceous fungi. Antifungal combination therapy is associated with improved outcomes in cerebral phaeohyphomycosis. In this study, we demonstrate that posaconazole is the single most active antifungal drug against this group of fungi. The double combination of amphotericin B with caspofungin or a trizole, and the triple combinations of caspofungin and flucytosine with amphotericin B or posaconazole might hold promise in the treatment of cerebral phaeohyphomycosis. Our findings will guide in developing optimal therapeutic strategies for these refractory infections.

Cerebral phaeohyphomycosis (CP) stands as an exceedingly uncommon yet severe type of fungal infection affecting the central nervous system, attributable to dematiaceous fungi. Despite the patient\'s immune status, CP is associated with grave prognosis. In the present study, authors describe the first case of left thalamic fungal abscess due to Rhinocladiella mackenziei in an immunocompetent 39-year-old male patient in Jaipur, Rajasthan. Early diagnosis by direct microscopy of aspirated pus and extensive management with surgical excision and prolonged antifungal coverage showed favourable outcome. The present case is one of the few cases documented globally who has survived.

暂无摘要。

OBJECTIVE: Cladophialophora bantiana is a wonted melanized fungus causing brain abscess. In past many cases were reported from Asia, particularly from India. Of late, there is a rise in cases in places besides Asia and hence a review of the cases is warranted.
METHODS: We present a case of fatal cerebral phaeohyphomycosis caused by C. bantiana and conduct a systematic review of culture confirmed brain abscess due to C. bantiana reported between 2015 and 2022.
RESULTS: Of the 39 cases found, majority (68%) were immunocompromised. The various clinical presentations were headache (53%), hemiparesis (34%), visual disturbance (25%), altered sensorium (18%), aphasia/dysarthria (12%) and seizures (9%). Isolated lesion was observed in 18 (60%) patients. In the sequence of occurrence, the lesions were in frontal (30%), temporal (27%) and parietal (20%) region. There were five cases with coinfections such as concurrent detection of Nocardia pneumonia in two cases, toxoplasma DNA in brain abscess, coexisting pulmonary Cryptococcus neoformans infection and coexisting Candida in a case of brain abscess in one case each. Surgical intervention was performed in 84% cases. Antifungal therapy included voriconazole (80%), liposomal amphotericin B (76%), 5-fluorocytosine (30%), posaconazole (10%), and amphotericin B deoxycholate (6%). The overall mortality was 50% with lower mortality (42%) in regions outside Asia compared to Asia (63.6%) though not statistically significant.
CONCLUSIONS: C. bantiana brain abscess is an emerging infection worldwide. Next generation sequencing is an upcoming promising diagnostic test. Early complete excision of the lesion with effective antifungals may improve the outcome.

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.
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.
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%.
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.
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.

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.

A right-handed man in his early 60s with hypertension controlled by a single prescription medication presented with left-sided heaviness and intermittent right occipital headache. Initial diagnostic workup was unremarkable. CT revealed an enhancing lesion located in the right parietal lobe, with mild mass effect on the right occipital horn, indicative of a brain abscess. The patient was initially treated with a course of empirical antibiotics, including ceftriaxone, vancomycin, metronidazole and dexamethasone. The neurosurgery team aspirated the abscess the following day and extracted yellow pus that was sampled for bacterial and fungal cultures. These cultures returned positive for Rhinocladiella mackenziei, prompting a discontinuation of the empirical antibiotics and initiation of intravenous liposomal amphotericin B for 4 weeks. Intravenous posaconazole was added to the patient\'s existing therapy regimen, which was substituted with oral isavuconazole on discharge. The patient continues to take isavuconazole, and follow-up imaging has demonstrated regression of the abscess.

OBJECTIVE: To report cases of cerebral phaeohyphomycosis at a tertiary hospital in Riyadh, Saudi Arabia. Phaeohyphomycetes are a widely distributed group of fungi whose cell walls contain 1,8 dihydroxynaphthalene-melanin. Cerebral infections caused by these fungi are uncommon and primarily associated with neurotrophic phaeohyphomycetes.
METHODS: In January of 2020 we looked back to identify cases of culture-positive cerebral phaeohyphomycosis from our medical records at King Faisal Specialist Hospital and Research Center in Riyadh, Saudi Arabia. Data on demographics, potential risk factors, clinical presentation, treatment, and outcomes were analyzed.
RESULTS: Twelve cases of cerebral phaeohyphomycosis were identified, of which 4 were caused by Rhinocladiella mackenziei and the other 8 were caused by various phaeohyphomycetes. There were 2 cases caused by Neoscytalidium dimidiatum, and one case each caused by the following: Acrophialophora fusispora, Chaetomium atrobrunneum, Exophiala dermatitidis, Exerohilum rostratum, Fonsecaea pedrosoi, and Cladophialophora bantiana. Most patients (10 of 12) had underlying immunosuppression. R. mackenziei caused a brain-only infection manifesting as abscess formation. Four patients survived for more than a year after therapy. Surgical evacuation and triazole therapy with posaconazole or itraconazole, alone or in combination with other antifungal agents, were associated with success.
CONCLUSIONS: Cerebral phaeohyphomycosis is an uncommon fungal infection that primarily affects immunocompromised patients and is associated with poor prognosis. R. mackenziei is the most prevalent fungus in our facility and has been linked to a universal mortality.

BACKGROUND: Neoscytalidiumdimidiatum is an opportunistic dematiaceous fungus belonging to the class Dothideomycetes.
METHODS: We report a case of N. dimidiatum cerebral phaeohyphomycosis post COVID-19 infection in a 32-year-old male from Iran. The causative agent was identified by cytopathology, routine mycological methods, and DNA sequencing of the internal transcribed spacer (ITS) region of rDNA. Apart from COVID-19 complications and the corticosteroid therapy, no underlying condition was diagnosed. The symptoms suggesting the fungal infection were shown two weeks after being discharged from COVID-19 hospital stay. Magnetic resonance of the brain showed a multi-focal central nervous system infection. The delayed identification of the fungus and, thus, a late starting of the antifungal treatment with amphotericin B, might have affected the patient outcome as he finally died.
CONCLUSIONS: Considering the rare incidence of N. dimidiatum infections, this case should aware us about them, leading to a timely antifungal management.

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.
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.
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.
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.