Cerebral Phaeohyphomycosis Research Articles

In vitro evaluation of antifungal combinations against neurotropic dematiaceous fungi associated with primary cerebral phaeohyphomycosis.

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.

Management and Outcome in a Case of Cerebral Phaeohyphomycosis Due to Rhinocladiella Mackenziei in an Immunocompetent Individual (P2-13.006)

Management and Outcome in a Case of Cerebral Phaeohyphomycosis Due to Rhinocladiella Mackenziei in an Immunocompetent Individual (P2-13.006)

Imaging in a rare case of cerebral phaeohyphomycosis caused by Cladophialophora bantiana in a renal transplant patient: a case report and the literature review

BackgroundCerebral phaeohyphomycosis is a rare and potentially life-threatening fungal infection caused by dematiaceous fungi (Levin TP et al. in J Clin Microbiol 42(9):4374–4378, 2004). It may occur in both immunocompetent and immunodeficient individuals, with a relatively higher incidence in the former (Revankar SG et al. in J Trop Med Hyg 38(1):206–222, 2004). A search of the Pubmed and Google Scholar databases revealed seven cases of cerebral phaeohyphomycosis in renal transplant patients caused by Cladophialophora bantiana (C. bantiana).Case presentationA 35-year-old male patient who had undergone a renal transplant presented with fever, imbalance while walking, and focal seizures involving the right lower limb. Magnetic Resonance Imaging (MRI) of the brain showed two lesions in the cerebral hemispheres. Craniotomy with excision of the lesion was done. The Periodic Acid Schiff (PAS) stain and the tissue culture on the Sabouraud dextrose agar suggested C. bantiana. The broad-spectrum antifungal drugs were started. However, the patient deteriorated in the subsequent follow-ups and eventually died of the disease.ConclusionsWe present a detailed report on the imaging characteristics of a rare fungal brain abscess caused by C. bantiana, which is the first case of its kind (refer to Table 1). In immunodeficient cases, intracranial pathologies can encompass a wide range of conditions, from infections to neoplasms, which often exhibit significant imaging overlap. In such a setting, the remote possibility of phaeohyphomycosis is easy to miss clinically and imaging-wise. MRI can narrow down the differential diagnosis and raise suspicion. In every suspicious case, it is of the utmost importance to correlate with the histopathology and the culture reports to initiate the prompt targeted therapy and avoid a fatal outcome. Complete excision of the abscess and antifungal agents like Voriconazole and Posaconazole are the mainstay of management in these patients.

48 A Case of an Extremely Rare CNS C. Bantiana Infection with Cognitive Sequela in an Immunocompetent Patient

Objective:Central nervous system (CNS) infections with the dematiaceous fungus Cladophialophora bantiana (C. bantiana) are extremely rare, with approximately 120 confirmed cases reported as of 2016. C. bantiana is a highly neurotropic and thermotolerant fungus found in soil worldwide. The mode of entry into the CNS remains unknown, but inhalation of fungal spores or subcutaneous trauma have been suggested. Entry of fungal spores can cause cerebral phaeohyphomycosis with the main clinical manifestation of a brain abscess. Symptoms are non-specific and can include headache, fever, hemiparesis, aphasia, visual disturbances, and confusion. C. bantiana cerebral phaeohyphomycosis occurs in both immunocompetent and immunocompromised individuals, with a slightly higher prevalence in immunocompetent males for unknown reasons. Diagnosis is often delayed due to its nonspecific presentation and prevalence in individuals without pre-existing immunological disease. Prognosis is poor, with mortality rates of approximately 70% despite aggressive treatment. Treatment is not standardized but may include several anti-fungal agents and surgical intervention. Case reports documenting the variability seen with cerebral phaeohyphomycosis by C. bantiana can provide valuable insight into this emerging disease. C. bantiana’s neurotropic propensity also warrants cognitive investigation of the disease; however, there are currently limited descriptions of cognitive findings in published case reports of C. bantiana CNS infections.Participants and Methods:Here, we describe a case of a 35-year-old immunocompetent, college educated male with a CNS C. bantiana infection, presumably following a fall while biking in Costa Rica. First symptoms included left sided facial palsy, headache, and hand weakness, prompting extensive diagnostic workup, with diagnosis of C. bantiana infection confirmed 8 months after symptom onset. Initial treatment included anti-fungal agents and steroids, but his course of infection was complicated by infectious vasculitis with posterior circulation infarcts and obstructive hydrocephalus requiring ventriculoperitoneal shunt placement two years following the fungal infection diagnosis. The most recent brain MRI revealed encephalomalacia in global periventricular areas, two small masses, likely representing small fungal phlegmons, and enhancing lesions in the upper cervical spinal canal.Results:The patient reported cognitive changes following the infarcts and shunt placement including difficulties with spatial navigation, following directions, and articulating thoughts. Memory concerns and lapses in judgment were also reported. Results from a neuropsychological evaluation revealed high average baseline intellectual abilities with decrements in visuospatial processing, processing speed, executive functioning, and aspects of memory stemming from his executive dysfunction. At the time, his cognitive profile suggested parietal and frontosubcortical systems disruption meeting criteria for mild cognitive impairment. Two years later, the patient reported continuing cognitive difficulties prompting a follow-up neuropsychological evaluation. Results were similar to his first evaluation, revealing deficits in aspects of visuospatial processing, decreased verbal and visual learning, bradyphrenia and processing speed deficits, and difficulties with visual planning and organization. Minimal anxiety and depression, but increased apathy and executive dysfunction were endorsed on self-report measures.Conclusions:This case report highlights neurological sequela resulting from CNS infection with C. bantiana, -with a course complicated by subsequent strokes, hydrocephalus, and cognitive impairment-, and contributes additional insight into the relatively limited existing reports of an extremely rare but emerging disease.

A Rare Case of Cladophialophora Isolated in a Renal Transplant Patient after Rejection Therapy

Cladophialophora bantiana is the most common cause of cerebral phaeohyphomycosis. A case of live-related renal allograft recipient complained of high-grade continuous fever on the 5th postoperative day (POD). No organism was isolated on cultures and no foci were found on chest X-ray. He was started on broad-spectrum antibiotics. The patient thereafter developed acute antibody-mediated plus acute cellular rejection on the 7th POD. He received a high dose methylprednisolone with plasmapheresis. On the 18th POD, the patient was diagnosed with right frontotemporal and basal ganglionic region abscess on magnetic resonance imaging of the brain. Urgent neurosurgical intervention was done and the sample was sent for investigation. Initially, there was suspicion of Aspergillus on culture. Injection of liposomal amphotericin B was given for 14 days, after which oral voriconazole was started. The patient improved initially but multiple abscesses recurred on the 46th POD. Abscess was drained. On the final culture report, C. bantiana was isolated. 5-flucytosine was added to voriconazole as dual antifungal therapy.

Cerebral phaeohyphomycosis at a tertiary healthcare center in Saudi Arabia

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. 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. 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. 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.

Fungal infection by Cladophialophora bantiana and development of cerebral phaeohyphomycosis. A systematic review of 58 case reports

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.

Magnetic resonance imaging and pathological characteristics of Cladophialophora encephalitis in a young dog

AbstractA 1‐year‐old dog was presented for persistent neck pain and circling. Magnetic resonance imaging revealed a large, space‐occupying, intra‐axial mass with extensive surrounding vasogenic oedema affecting the left thalamus and hippocampus. Postmortem histopathology of the brain lesion identified fungal hyphae with significant local brain reaction. Fungal sequencing confirmed Cladophialophora bantiana. Magnetic resonance imaging findings can look similar to other inflammatory processes or even neoplasia. While histopathology of the lesions may not always identify fungal hyphae, it will often confirm necrosis, pyogranulomatous inflammation and perivascular cuffing with lymphocytes. Cerebral phaeohyphomycosis should be included in the differential diagnosis list in a young dog with intracranial neurologic deficits.

Phaeohyphomycosis caused by Neoscytalidiumdimidiatum in a COVID-19 patient

BackgroundNeoscytalidiumdimidiatum is an opportunistic dematiaceous fungus belonging to the class Dothideomycetes. Case reportWe 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. ConclusionsConsidering the rare incidence of N. dimidiatum infections, this case should aware us about them, leading to a timely antifungal management.

Phaeohyphomycosis in China

BackgroundDue to more attentions paid to melanized fungi over the past few decades and under the background of the global coronavirus disease 2019 pandemic (COVID-19) the fact that the virus itself and the immunosuppressive agents such as glucocorticoids can further increase the risk of infections of deep mycoses, the number of patients with phaeohyphomycosis (PHM) has a substantial increase. Their spectrum is broad and the early diagnosis and treatments are extremely sticky. This study aims to more comprehensively understand the clinical features of phaeohyphomycosis in China over 35 years and to establish a more applicable systematical classification and severity grades of lesions to guide treatments and prognosis.MethodsWe reviewed 174 cases of proven phaeohyphomycosis reported in Chinese and English language literature from 1987 to 2021 and we also made the accurate classification definitions and detailed information about the epidemiology, species of clinical dematiaceous fungi, minimum inhibitory concentration values, clinical features, treatments, and prognosis.ResultsThe mortality of cerebral, disseminated and pulmonary phaeohyphomycosis are 55%, 36%, and 25%. Nearly 19% of patients had poor quality of life caused by the complications such as disability, disfigurements, and blindness. The overall misdiagnosis rate of phaeohyphomycosis was 74%. Moderate to severe rashes are accounting for 82% of subcutaneous phaeohyphomycosis. The areas of the head and face are mostly affected accounting for 16% of severe rashes. Nearly 30% of invasive infections of phaeohyphomycosis are triggered by recurrent lesions. Voriconazole, itraconazole, amphotericin B deoxycholate (AmB-DOC), and terbinafine were most commonly used but diagnosis and treatments of phaeohyphomycosis remain challenging in reality.ConclusionsOur classifications are likely to be more practical and easier to popularize, and there are still also plenty of characteristics in these non-specific lesions. There’re no significant variations in cure rates, or death rates between three grades of lesions. But patients with severe rashes have longer courses and lower effective rates.

Cerebral phaeohyphomycosis: The ‘Dark Side’ of fungal infections

PurposeCerebral 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 methodsData 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. ResultsThree 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. ConclusionCerebral 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.

Utility of liquid biopsy in diagnosing isolated cerebral phaeohyphomycosis: illustrative case.

BACKGROUNDCladophialophora bantiana is a dematiaceous, saprophytic fungus and a rare but reported cause of intracranial abscesses due to its strong neurotropism. Although it predominantly affects immunocompetent individuals with environmental exposure, more recently, its significance as a highly lethal opportunistic infection in transplant recipients has been recognized. Successful treatment requires timely but often challenging diagnosis, followed by complete surgical excision. Next-generation sequencing of microbial cell-free DNA (cfDNA) from plasma is a novel diagnostic method with the potential to identify invasive fungal infections more rapidly and less invasively than conventional microbiological testing, including brain biopsy.OBSERVATIONSThe authors described the case of a recipient of a liver transplant who presented with seizures and was found to have innumerable ring-enhancing intracranial lesions. The Karius Test, a commercially available method of next-generation sequencing of cfDNA, was used to determine the causative organism. Samples from the patient’s plasma identified C. bantiana 6 days before culture results of the surgical specimen, allowing optimization of the empirical antifungal regimen, which led to a reduction in the size of the abscesses.LESSONSThe authors’ findings suggest that microbial cfDNA sequencing may be particularly impactful in improving the management of brain abscesses in which the differential diagnosis is wide because of immunosuppression.

Gram stain to the rescue: a case report of cerebral phaeohyphomycosis by Cladophialophora bantiana in an immunocompetent 24-year-old

BackgroundFungal brain abscesses in immunocompetent patients are exceedingly rare. Cladophialophora bantiana is the most common cause of cerebral phaeohyphomycosis, a dematiaceous mold. Radiological presentation can mimic other disease states, with diagnosis through surgical aspiration and growth of melanized fungi in culture. Exposure is often unknown, with delayed presentation and diagnosis.Case presentationWe present a case of cerebral phaeohyphomycosis in a 24-year-old with no underlying conditions or risk factors for disease. He developed upper respiratory symptoms, fevers, and headaches over the course of 2 months. On admission, he underwent brain MRI which demonstrated three parietotemporal rim-enhancing lesions. Stereotactic aspiration revealed a dematiaceous mold on staining and the patient was treated with liposomal amphotericin B, 5-flucytosine, and posaconazole prior to culture confirmation. He ultimately required surgical excision of the brain abscesses and prolonged course of antifungal therapy, with clinical improvement.ConclusionsCulture remains the gold standard for diagnosis of infection. Distinct microbiologic findings can aid in identification and guide antimicrobial therapy. While little guidance exists on treatment, patients have had favorable outcomes with surgery and combination antifungal therapy. In improving awareness, clinicians may accurately diagnose disease and initiate appropriate therapy in a more timely manner.

Answer to July 2021 Photo Quiz.

Answer: Phaeohyphomycosis caused by Exophiala oligosperma. The mold was identified as Exophiala oligosperma (a member of the Exophiala jeanselmei complex) based on sequencing of the internal transcribed spacer (ITS). Amplification of the ITS region was performed using previously described fungus-specific primers ITS1 (5′-TCCGTAGGTGAACCTGCGG-3′) and ITS4 (5′-TCCTCCGCTTATTGATATGC-3′) (1). Sanger sequencing indicated 100% match by BLAST with Exophiala oligosperma. The E. jeanselmei complex consists of dematiaceous saprobic fungi (2). In addition to E. oligosperma and E. jeanselmei, they include species such as E. heteromorpha, E. lecanii-corni, and E. xenobiotica (3). These fungi are very similar morphologically and are largely separated by molecular differentiation. Identification of Exophiala spp. to the species level may not be necessary due to similar ranges of clinical infections, with the exception of Exophiala dermatitidis (4–6). E. dermatitidis is neutroropic, with a propensity for causing cerebral phaeohyphomycosis. Other Exophiala spp. can cause infections particularly in immunocompromised people, commonly through direct inoculation (4), causing inflammation in the subcutaneous and cutaneous tissues and the formation of mycetoma, a chronic inflammatory granulomatous disease. The infection may potentially disseminate systemically and lead to arthritis and endocarditis in immunocompromised patients (4, 5). E. jeanselmei complex grows optimally at 30°C. Isolates from humans can grow at 37°C but are inhibited at 40°C. This evolutionary adaptation helped the complex’s survival on human hosts. Inhibition at 40°C and in 15% salinity, with growth in the presence of cycloheximide, is useful in differentiating E. jeanselmei complex from similar molds, such as Exophiala dermatitidis and Hortaea werneckii. Exophiala dermatitidis can grow at 40°C (7), while Hortaea werneckii is inhibited by cycloheximide and is able to grow in 15% saline. Use of matrix-assisted laser desorption–ionization time of flight mass spectrometry (MALDI-TOF MS) may also be considered for accurate identification. However, this is dependent on the availability of a reliable database (5). Torulose hyphae (see Fig. 1B and C in the photo quiz) are present in Exophiala spp. but may appear yeast-like on histological samples. Staining of melanin with the Fontana-Masson stain was not performed in our case but may be considered and could help differentiate dematiaceous molds from Candida spp. Dematiaceous molds appear pigmented on culture because of melanin in their cell walls. The melanin acts as a virulence factor via its scavenging effect on free radicals and hypochlorite, which are produced by phagocytic cells, and via binding to hydrolytic enzymes (8).

Comment on “is Phaeohyphomycosis an emerging fungal Infection in Iran? A Short Communication

Dear editor We recently read an interesting article entitled “Is Phaeohyphomycosis an emerging fungal Infection in Iran? A Short Communication” [1] which is published in your journal. This article discusses the prevalence of Phaeohyphomycosis cases in Iran. We published an article entitled “Cerebral Phaeohyphomycosis due to Rhinocladiella mackenziei in Persian Gulf region: A case and review” in 2018 [2]. Our case was a diabetic patient with the history of behcet's disease and with the diagnosis of brain abscesses due to Rhinocladiella mackenziei. For the patient we prescribed voriconazole at first then change the regimen to amphotericin b liposomal (5 mg/kg/day) with combination of posaconazole (200 mg every 6 hours). In the article published by zarrinfar et al recently [1], the authors have referenced our article [2] and instead of the original dose for posaconazole (200 mg every 6 hours), which we also had stated the dose in our article (200 mg every 6 hours), the authors have written wrong dose (200 mg daily) in the table. The dose of posaconazole for treatment is 200 mg every 6 hours and for prophylaxis is 200 mg every 8 hours. We request that this wrong dose be corrected in the table of article published in your journal.

Cerebral phaeohyphomycosis due to Rhinocladiella mackenziei in an immunocompetent patient: A case report and review of literature

Background: Rhinocladiella mackenziei is a neurotropic fungus which is unique in its ability to cause a devastating cerebral infection with upto 100% fatality rate both in immunocompromised and immunocompetent individuals despite aggressive treatment with surgery and intensive antifungal therapy. Cerebral phaeohyphomycosis formation of pus and black necrotic debris leading to development of brain abscesses. Rhinocladiella mackenziei is difficult to isolate in laboratory as it grows slowly in culture medium, requiring skill to diagnose it. Case description: A 42-year-old Pakistani man presented with left frontal and retro-orbital headache, left facial numbness and progressive right upper limb weakness and speech difficulty. Magnetic resonance imaging (MRI) of Brain with contrast showed a space occupying lesion in the basal ganglia region. All other workup was unremarkable. He underwent neuronavigation guided supratentorial craniotomy for biopsy and excision of the left thalamic space occupying lesion. Histopathology of specimen revealed abscess formation with few scattered granulomas showing collections of histiocytes and multinucleated giant cells. Periodic Acid-Schiff (PAS) special stains highlighted numerous septate fungal hyphae. Culture later grew Rhinocladiella Mackenziei. He developed complications during his hospital stay but is currently stable and is being treated with Amphotericin and Posaconaole along with neurorehabilitation therapy. Discussion:Rhinocladiella mackenziei, has been recognized to cause cerebral phaeohypomycosis. It has been suggested that inhalation of fungal spores is presumed source of entry of the organism. Our patient had a single ring enhancing lesion in the basal ganglia region.Upon operation the infected area looks greenish-brown in color with thick wall abscess cavity containing purulent material.The commonly used antifungal agents are amphotericin B, posaconazole, voriconazole and itraconazole.Our patient received amphotericin and posaconazole.The treatment duration varies from 3 months to a year and is guided by complete resolution of symptoms and radiological findings.Our patient's GCS has improved but right sided weakness and aphasia persists upon completion of one month of treatment. Conclusion: Rhinocladiella mackenzei brain abscess is a devastating infection with significant morbidity and mortality and should be suspected in patients presenting with brain abscess from high endemic areas.

Cerebral Phaeohyphomycosis Due to Cladophialophora Bantiana in a Kidney Transplant Patient

Abstract Casestudy: Phaeohyphomycosis is a group of infections caused by pigmented, black, dematiaceous fungi and is responsible for cutaneous, superficial and deep mycoses, disseminated infection and brain abscesses. The primary agents involved include Alternaria spp., Exophiala spp. and Cladophialophora spp. Cerebral phaeohyphomycosis is particularly devastating with mortality rates as high as 70-80%. These fungi are becoming increasingly important opportunistic pathogens in solid organ transplant recipients (SOTR). We report a case of cerebral phaeohyphomycosis in a 65-year-old male with living donor kidney transplant for four years and has been maintained on immunosuppressive therapy with tacrolimus and prednisone. The patient presented with aphasia, frontal headache, loss of peripheral vision of right eye, and mental status change for three months due to several left- sided parieto-occipital brain abscesses. Left occipital abscess resection and parietal partial lobectomy were performed to reduce intracranial hypertension and to remove abscesses. Histopathological evaluation revealed brain abscess with pigmented fungal organisms with elongated, branched and septate. The pus aspirated during surgical excision of brain lesions grew black mold, identified as Cladophialophora bantiana. The patient’s neurological neurological condition had imporved after several weeks of combination antifungal therapy with posaconazole, liposomal amphotericin, and flucytosine. The lesions were initially suspected to be of tuberculous etiology, which was ruled out by histopathological examination. Such diagnostic dilemmas are common in the infection caused by Cladophialophora, which can cause treatment delay and death. Early diagnosis is therefore mandatory for the rapid treatment and survival of patients. As the number of SOTR increases, so does the incidence of fungal infections in that population. Surgery, along with antifungal therapy and a reduction in immunosuppression, are the cornerstones of treatment.

A rare case of fatal cerebral phaeohyphomycosis caused by Cladophialophora bantiana in an immunocompetent individual in India.

Background and Purpose: Herein, we describe a rare case of fatal cerebral phaeohyphomycosis by Cladophialophora bantiana in an immunocompetent individual without any underlying risk factors.Case report: A 55-year-old female presented with a short history of fever for 1 month, as well as headache, sudden onset of right-sided upper and lower limb weakness, and loss of speech for 10 days. Contrast-enhanced magnetic resonance imaging scan revealed large, peripherally enhancing, well-defined, cystic, space- occupying, axial lesion in the left parietal lobe with a mass effect. The patient was subjected to craniotomy, and the drained pus revealed pigmented septate hyphae in potassium hydroxide mount examination, which was identified as Cladophialophora bantiana. The patient was started on amphotericin B and voriconazole. However, she developed acute respiratory infection leading to multi-organ failure and death on day 27 post-operation.Conclusion: In the absence of comparative trials owing to the rarity of the disease, the radical resection of lesion, drainage of pus, and prolonged targeted antifungal therapy with close postoperative radiological surveillance are the therapeutic measures of choice for patients with brain abscess caused by phaeoid fungi.

Cerebral phaeohyphomycosis due to Rhinocladiella mackenziei in an immunocompetent patient: A case report and review of literature.

Background and Purpose: Rhinocladiella mackenziei is a neurotropic fungus, which can cause devastating intracerebral infections with up to 100% fatality rate. It is difficult to isolate this fungus in laboratory as it grows slowly and requires diagnostic skills.Case report: A 42-year-old Pakistani man presented with headache, facial numbness, progressive upper limb weakness, and dysarthria. Magnetic resonance imaging of the brain showed a space-occupying lesion in the basal ganglia region. The patient underwent supratentorial craniotomy for biopsy and excision. Histopathology of the specimen revealed granulomatous inflammation with abscess formation. Periodic acid- Schiff special stains highlighted the presence of numerous septate fungal hyphae. The results revealed the growth of dematiaceous fungi, which were morphologically classified as R. mackenziei. The patient is currently stable and is being on amphotericin and posaconazole, along with neurorehabilitation therapy.Conclusion: Rhinocladiella mackenziei brain abscess is a devastating infection with significant mortality. This condition should be suspected in patients with brain abscess from high endemic areas.

Cerebral Phaeohyphomycosis: A Rare Case from South India

Background and Importance: Cerebral phaeohyphomycosis is a rare but frequently fatal clinical entity caused by dematiaceous fungi like Cladophialophora bantiana. Fungal brain abscess often presents with subtle clinical symptoms and signs, and present diagnostic dilemma due to its imaging appearance that may be indistinguishable from other intracranial space-occupying lesions. Still, certain imaging patterns on Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) help to narrow down the differential diagnosis and initiate prompt treatment of these infections. Case Presentation: A 48-year-old immunocompetent man presented with right-sided hemiparesis and hemisensory loss and a provisional diagnosis of stroke was made. The radiological evaluation suggested the possibility of a cerebral abscess. Accordingly, surgical excision of the lesion was performed and the histopathological examination of the specimen revealed the etiology as phaeohyphomycosis. The patient was further treated with antifungals and discharged when general conditions improved. Conclusion: Fungal Central Nervous System (CNS) infections present diagnostic challenges and should be considered while interpreting ring-enhancing CNS lesions in immunocompetent patients. Surgical resection and antifungal treatment should be considered in all patients with cerebral phaeohyphomycosis.