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.

Disseminated cerebral cryptococcoma mimicking glioblastoma - A case report."

We discuss a rare instance of cryptococcoma caused by Cryptococcus gattii in a 55-year-old woman initially treated for suspected COVID bronchopneumonia. The diagnosis posed a challenge due to vague symptoms and unclear imaging findings suggesting malignancy. Postoperative samples confirmed the presence of Cryptococcus gattii through culture of brain tissue and blood. Appropriate therapy was initiated, but despite treatment, it led to a fatal outcome. The case emphasizes the crucial role of microbiologist in early diagnosis of fungal infections of Central Nervous System. Additionally, the delayed diagnosis in immunocompetent individuals highlights the critical need for early recognition and intervention to mitigate potentially fatal outcomes.

Psychiatric manifestations of neurosyphilis over past two decades: Findings from a tertiary care neuropsychiatric hospital in south India.

OBJECTIVE: To assess presentation of neurosyphilis with a focus on the psychiatric aspects. METHOD: File review of the cases with a positive cerebrospinal fluid venereal disease research laboratory test between 1999 to 2020. RESULTS: Medical records of 143 neurosyphilis patients were analysed. Hallucinations, delusions, and catatonia were the commonest psychiatric symptoms. Brain atrophy was the commonest neuroimaging finding. The number of neurosyphilis patients and the proportion with delirium or catatonia declined during the second decade (2010-2020). CONCLUSION: Atypical presentation of psychiatric symptoms around the fifth decade, with associated neurological symptoms or brain imaging changes, should prompt evaluation for neurosyphilis.

First report of COVID-19-associated rhino-orbito-cerebral mucormycosis in pediatric patients with type 1 diabetes mellitus.

Coronavirus disease 2019 (COVID-19) is a major public health problem worldwide. These patients are at increased risk of developing secondary infections due to a combination of virus- and drug-induced immunosuppression. Recently, several countries have reported an emergence of COVID-19 associated mucormycosis (CAM), particularly among patients with uncontrolled diabetes, with India reporting an alarming increase in rhino-orbito-cerebral mucormycosis (ROCM) in post-COVID cases. Hyperglycemia and diabetic ketoacidosis (DKA) are the major underlying risk factors. So far, case reports and review articles have reported CAM only in adult patients. Here, we describe the first cases of COVID-19-associated ROCM in two pediatric patients with Type 1 diabetes mellitus (DM). Both the cases had asymptomatic infection with SARS-CoV-2 and developed ROCM during the course of treatment of DKA. None of them had exposure to systemic steroids. Imaging findings in both cases revealed involvement of orbit, paranasal sinuses, and brain with cavernous sinus thrombosis. The patients underwent craniotomy with evacuation of abscess. Microbiological and histopathological findings were consistent with the diagnosis of mycormycosis, with fungal culture growing Rhizopus arrhizus. Post-operatively, the patients received liposomal amphotericin B (LAMB) and systemic antibiotics. Retrobulbar injection of LAMB was given in an attempt to halt orbital disease progression. However, it wasn't successful and both of them had to undergo orbital exenteration eventually. ROCM is a rapidly progressive disease and prompt diagnosis with aggressive surgery and timely initiation of antifungal therapy can be life-saving. Physicians should have a high index of suspicion, so as to avoid a delayed diagnosis, particularly in post-COVID patients with uncontrolled diabetes.

A pneumococcal brain abscess: a case report.

A brain abscess which is caused by Streptococcus pneumoniae is a rare entity. Here, we have described a gentle man who presented with the signs and symptoms of a mass lesion which was localized to the temporal lobe. The clinical examination and computerized tomography revealed the diagnosis of a temporal abscess. The loculated mass was tapped and it was sent for histopathology, which confirmed the presence of an organizing abscess. A laboratory investigation of the pus revealed Streptococcus pneumoniae. The treatment included total excision and the administration of prolonged antibiotics, which led to a good outcome in the patient.