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.

Combination of Amphotericin B and Flucytosine against Neurotropic Species of Melanized Fungi Causing Primary Cerebral Phaeohyphomycosis.

Primary central nervous system phaeohyphomycosis is a fatal fungal infection due mainly to the neurotropic melanized fungiCladophialophora bantiana,Rhinocladiella mackenziei, andExophiala dermatitidis.Despite the combination of surgery with antifungal treatment, the prognosis continues to be poor, with mortality rates ranging from 50 to 70%. Therefore, a search for a more-appropriate therapeutic approach is urgently needed. Ourin vitrostudies showed that with the combination of amphotericin B and flucytosine against these species, the median fractional inhibitory concentration (FIC) indices for strains ranged from 0.25 to 0.38, indicating synergy. By use of Bliss independence analysis, a significant degree of synergy was confirmed for all strains, with the sum ΔE ranging from 90.2 to 698.61%. No antagonism was observed. These results indicate that amphotericin B, in combination with flucytosine, may have a role in the treatment of primary cerebral infections caused by melanized fungi belonging to the orderChaetothyriales Furtherin vivostudies and clinical investigations to elucidate and confirm these observations are warranted.

First fatal cerebral phaeohyphomycosis due to Rhinocladiella mackenziei in Iran, based on ITS rDNA.

Black yeast-like fungi and relatives as agents of cerebral phaeohyphomycosis are often encountered in human fatal brain abscesses and lead to almost 100% mortality despite the application of antifungal and surgical therapy. We report to our knowledge the first case of brain infection due to Rhinocladiella mackenziei in a 54-year-old immunocompetent male in Iran where R. mackenziei has not been reported previously. The initial diagnosis was brain fungal infection because of pigmented, irregular, branched, septated hyphae based on histopathological staining. The patient was treated with intravenous amphotericin B deoxycholate (0.5mg/kg/day) combined with oral itraconazole (200mg twice daily), nevertheless, his neurological function deteriorated rapidly and ultimately the patient died due to respiratory failure later two weeks. R. mackenziei was identified based on the sequencing of internal transcribed spacer (ITS rDNA region) (KJ140287). Therefore, considerable attention for this life-threatening infection is highly recommended.

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.

[Fungal infections of the central nervous system in the immunocompetent host]. / Pilzinfektionen des Zentralnervensystems bei immunkompetentem Wirt.

The majority of mycoses which lead to mycotic tumors in patients without any predisposing underlying disease are either caused by Cryptococcus gattii and C. neoformans or by dematiaceous fungi which include Cladophialophora bantiana, Ramichloridium mackenziei, Exophiala and Fonsecaea species. The detection of hyphae in granuloma in the brain should lead to screening for pigmented fungi, which are recognized best in hematoxylin eosin (HE) or sometimes also in periodic acid-Schiff (PAS) stained sections. In patients who survive a near drowning accident and those who develop brain abscesses, scedosporiosis should always be considered as a possible infection.

Successful management of an intracranial phaeohyphomycotic fungal granuloma in a dog.

CASE DESCRIPTION: A 12-month-old castrated male Boxer was examined because of signs of acute, progressive intracranial disease. CLINICAL FINDINGS: Cytologic and histologic findings were consistent with an intracranial fungal granuloma in the right cerebral hemisphere. Fungal culture yielded a Cladophialophora sp. TREATMENT AND OUTCOME: The granuloma was surgically debulked to remove infected brain tissue and the avascular purulent core. Postoperatively, the patient was treated with fluconazole (2.3 mg/kg [1 mg/lb], PO, q 12 h) for 4 months, followed by voriconazole (3.4 mg/kg [1.5 mg/lb], PO, q 12 h) for a further 10 months. The outcome was considered excellent on the basis of resolution of neurologic signs and a lack of evidence of recurrence of the granuloma during magnetic resonance imaging and CSF analysis 8 months after surgery. Magnetic resonance imaging and CSF analysis 9 weeks after administration of antifungal medications was discontinued (16 months after surgery) confirmed resolution. CLINICAL RELEVANCE: Intracranial phaeohyphomycosis in small animals is rare and is most commonly associated with Cladophialophora infection. Phaeohyphomycosis frequently causes a focal granuloma, whereas other fungal infections typically cause diffuse meningoencephalitis. In all previous reports of phaeohyphomycosis of the CNS in dogs, treatment has been limited to medical management with conventional antifungal drugs and had failed to prevent death. The present report suggested that combined management of granulomas with surgery and newer triazole medications such as voriconazole may represent a novel strategy that improves the prognosis for this disease.