Ventriculitis due to Aspergillus fumigatus in a child with central nervous system tuberculosis

C. Antachopoulos1, T. Stergiopoulou1, M. Simitsopoulou1, E. Georgiadou1, S. Kottas1, D. Marinopoulos1, A. Anastasiou2, E. Roilides1

Author address: 

1Aristotle University, THESSALONIKI, Greece 2Hippokration Hospital, THESSALONIKI, Greece


Objectives: Central nervous system (CNS) aspergillosis in immunocompromised patients usually presents with brain lesions (abscesses) and carries a poor prognosis. Reports of Aspergillus meningitis / ventriculitis are rare. We present a case of ventriculitis due to A. fumigatus to highlight its features and outcome and we report the results of the intraventricular antifungal activity on systemic antifungal therapy. Methods: Case report and ex vivo evaluation of antifungal activity of cerebrospinal fluid (CSF) against A. fumigatus isolate. The antifungal effect of CSF was studied by incubating undiluted CSF samples for 1/2, 1, 2 or 4 h with pre-grown hyphae of the patient’s Aspergillus isolate and assessing hyphal damage using a modified XTT assay. Case and results: We present a case of ventriculitis due to A. fumigatus in a 5-year old girl with refractory CNS tuberculosis. At the time of presentation she was on isoniazid, rifampin, pyrazinamide, levofloxacin and high-dose dexamethasone (0.8 mg/kg/d) started 4 weeks ago due to neurological complications of tuberculosis. She also had a ventriculoperitoneal shunt due to hydrocephalus. A febrile episode of shunt infection led to removal of the device; cultures of both the valve and catheter revealed A. fumigatus. The patient was started on liposomal amphotericin B (LAMB) at 7 mg/kg/d. Dexamethasone dose was gradually reduced. MICs of A. fumigatus isolate to both amphotericin B and voriconazole were 8804;0.25μg/ml by CLSI method. Fevers persisted and CSF examination revealed neutrophilic pleocytosis with negative bacterial and fungal cultures. Aspergillus PCR in the CSF was positive as well as galactomannan index (5.5). An MRI brain scan revealed no new parenchymal lesions; however, areas of increased signaling in the ventricles suggested ventriculitis. Voriconazole (8mg/kg/d) was added while rifampin was discontinued to avoid interference with voriconazole metabolism. Intraventricular administration of amphotericin B deoxycholate (DAMB) was also commenced at a dose of 5 mg, followed by 2.5 mg every other day for one month. Fevers subsided and CSF galactomannan ratios gradually decreased, becoming persistently negative after 3 months of antifungal treatment. Duration of therapy with LAMB and voriconazole was 4 and 5 months respectively. During the first month of combined systemic and intraventricular antifungal treatment CSF was collected after intraventricular DAMB administration, at 2 h as well as at 48 h (i.e. before the next intraventricular dose). The mean hyphal damage (two separate experiments) caused by CSF samples obtained 2 h post DAMB administration was 78%, 93%, 97% and 96% for 1/2, 1, 2 or 4 h incubation periods respectively. Corresponding hyphal damage values obtained with CSF collected 48 h post DAMB administration were 28%, 57%, 57% and 71% (p

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Full conference title: 

4th Trends in Medical Mycology
    • TIMM 4th (2012)