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.

A 3-year-old boy presented with acute headache, vomiting and right focal clonic seizures without history of fever, joint pain or altered sensorium. Neuroimaging showed multifocal contrast enhancing lesions with significant perilesional edema. CECT chest and abdomen showed multiple variable sized nodules in the lungs and hypodense lesion in liver with mesenteric lymphadenopathy. There was persistent eosinophilia with maximum upto 35 %. Liver biopsy and brain biopsy revealed Cladophialophora bantiana. He was treated with IV liposomal amphotericin and voriconazole for 6 weeks with repeat neuroimaging showing more than 50 % resolution of the intracranial lesions. He was transitioned to oral combination of flucytosine and voriconazole. At 14 months follow-up, he remained symptom free with complete radiological resolution of the lesions and no eosinophilia. High suspicion, an aggressive approach in obtaining microbiological diagnosis and timely combination antifungal therapy may give satisfactory outcome without surgery.

UNASSIGNED: Amongst the infections in kidney transplant recipients, brain abscess represents an uncommon life-threatening complication. Mortality continues to be high despite improvements in diagnostics and therapeutics.
UNASSIGNED: We conducted an observational study, describing the incidence, presentation, implicating pathogen, management and outcome of brain abscess following kidney transplantation at our centre.
UNASSIGNED: Amongst the 1492 patients who underwent kidney transplantation at our centre between June 1991 and January 2023 (cumulative follow-up: 4936 patient-years), five females and four males, developed brain abscesses. The incidence proportion (risk) is 0.6% with an incidence rate of 6.03 cases per 1000 patient years. The median duration from transplant to development of brain abscess was 5 weeks (range: 4 weeks to 9 years). The commonest presentation was a headache. A definitive microbiological diagnosis was established in eight out of nine patients. The commonest implicated organism was a dematiaceous fungus, Cladophialophora bantiana (3 patients, 33.3%). Despite the reduction in immunosuppression, surgical evacuation and optimal medical therapy, five (55.55%) patients succumbed to their illness.
UNASSIGNED: Brain abscesses following kidney transplantation is an uncommon, life-threatening condition. It usually occurs in the early post-transplant period and the presentation is often subtle. Unlike immunocompetent individuals, a fungus is the most common causative organism in those with solid organ transplants. The management includes a reduction in immunosuppression, early antimicrobial therapy, and surgical decompression.

Cladophialophora and other dematiaceous or pigmented fungi are inhabitants of soil and decaying vegetation in tropical and sub-tropical environments. It usually causes subcutaneous phaeohyphomycosis post-inoculation by thorns or vegetable matter prick. It may be inhaled into paranasal sinuses and lungs with subsequent clearance by intact host immunity. In immunocompromised individuals, it can cause invasive sinusitis or pneumonitis followed by hematogenous dissemination to involve distant organs, particularly the brain. Disseminated disease with hematogenous brain abscess is found occasionally. We encountered such an interesting case and successfully treated it with surgical drainage followed by dual anti-fungal therapy.

Sugarcane (Saccharum officinarum, Poaceae) is cultivated on a large scale in (sub)tropical regions such as Brazil and has considerable economic value for sugar and biofuel production. The plant is a rich substrate for endo- and epiphytic fungi. Black yeasts in the family Herpotrichiellaceae (Chaetothyriales) are colonizers of human-dominated habitats, particularly those rich in toxins and hydrocarbon pollutants, and may cause severe infections in susceptible human hosts. The present study assessed the diversity of Herpotrichiellaceae associated with sugarcane, using in silico identification and selective isolation. Using metagenomics, we identified 5833 fungal sequences, while 639 black yeast-like isolates were recovered in vitro. In both strategies, the latter fungi were identified as members of the genera Cladophialophora, Exophiala, and Rhinocladiella (Herpotrichiellaceae), Cyphellophora (Cyphellophoraceae), and Knufia (Trichomeriaceae). In addition, we discovered new species of Cladophialophora and Exophiala from sugarcane and its rhizosphere. The first environmental isolation of Cladophialophora bantiana is particularly noteworthy, because this species up to now is exclusively known from the human host where it mostly causes fatal brain disease in otherwise healthy patients.

A 75-year-old immunocompetent male presented with a right orbital cellulitis after a foreign body penetrating injury. He was taken for orbitotomy with foreign body removal and started on broad-spectrum antibiotics. Intra-operative cultures were positive for Cladophialophora bantiana, a mold known for causing brain abscesses with no prior reports of orbital invasion in the literature. Following culture results, the patient was managed with voriconazole and required multiple orbitotomies and washouts for infection control.

Recipients of solid organ transplants are at risk for a variety of infections due to their immunocompromised status. The types of infections are often correlated to the timing from their transplant. After about six to twelve months, transplant recipients remain at risk for typical community acquired pathogens, late viral infections, and fungal infections including atypical molds such as Cladophialophora bantiana. C. bantiana is a dematiaceous fungus that has a predilection for infecting the brain and is the most common cause of cerebral phaeohyphomycosis - a term used to describe infections caused by molds that produce dark cell walls. Patients with cerebral abscesses due to C. bantiana infections have an estimated mortality of about 70%. Improved outcomes have been seen in patients who receive both surgical and antifungal therapy. While there are no clear guidelines on antifungal therapy, most cases have been treated with combination amphotericin B, a triazole (itraconazole, voriconazole, or posaconazole) with flucytosine sometimes in conjunction as well. This case describes a patient with C. bantiana brain abscess and concurrent Cryptococcus neoformans pulmonary infection that occurred twenty years after his kidney transplantation. He was treated successfully with two craniotomies for cerebral abscess debridement and liposomal amphotericin B followed by planned lifelong voriconazole.

UNASSIGNED: Cladophialophora bantiana is a dematiaceous fungus that rarely infects the central nervous system (CNS). It is associated with a mortality rate of over 70% despite treatment.
UNASSIGNED: An 81-year-old female with a remote history of renal cell carcinoma presented with progressive headache and an expressive aphasia for 3 days. Computed tomography imaging revealed a left frontotemporal mass with surrounding vasogenic edema. A left frontotemporal craniotomy was performed and cultures revealed C. bantiana. The initial management with IV voriconazole was unsuccessful and the patient had a recurrence of the cranial infection and developed pulmonary abscesses. Following the addition of oral flucytosine, the patient showed a significant improvement with a complete radiographic resolution of both the cranial and pulmonary lesions.
UNASSIGNED: C. bantiana involving the CNS is a rare and often fatal disease. Surgical management along with standard antifungal treatment may not provide definitive therapy. The addition of flucytosine to IV voriconazole resulted in a positive outcome for this patient who is alive, living independently 1 year from the original diagnosis. In this rare fungal infection, standard antifungal treatment may not provide adequate coverage and the utilization of additional therapy may be required.

BACKGROUND: Cladophialophora bantiana, a neurotropic phaeoid fungus, is the primary agent of cerebral phaeohyphomycosis. The disease more commonly affects immunocompetent males and is associated with a high mortality rate.
METHODS: We report a case of brain abscess caused by Cladophialophora bantiana in a 50-year-old immunocompetent male who presented with headache for two months, weakness of both lower limbs for 15 days, and altered sensorium and aphasia for one day. Contrast-enhanced MRI of the brain showed multiple coalescent abscesses in the right basal ganglia and corpus callosum. Based on clinical and radiological suspicion of tuberculoma, treatment with antitubercular drugs was initiated. A month after discharge, the patient was re-admitted with history of loss of consciousness, altered sensorium, respiratory distress and aphasia. Brain CECT revealed multiple ring-enhancing lesions in the right basal ganglia with mass effect and a leftward midline shift. The patient underwent craniotomy and evacuation of abscess. Direct microscopy of pus aspirated from the lesions showed pigmented septate fungal hyphae, which was identified as C. bantiana in fungal culture. The patient was administered intravenous liposomal amphotericin B and voriconazole. However, he died due to multiple organ failure on day 19 after surgery.
CONCLUSIONS: Fungal etiology should be considered in the differential diagnosis of intracranial space occupying lesions, regardless of the host immune status. An early diagnosis, together with aggressive medical and neurosurgical interventions are imperative for improving the survival in such patients.

BACKGROUND: Fungal 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.
METHODS: We 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.
CONCLUSIONS: Culture 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.