Intrathecal amphotericin B therapy in a patient with X-linked chronic granulomatous disease and refractory cerebral invasive aspergillosis

Introduction: Invasive aspergillosis (IA) is one of the lifethreatening complications in CGD patients, and represents a major cause of morbidity and mortality. The main therapy is the IV- injection of antifungal agents, as Voriconazole and Amphotericin-B. However, the mortality rate is very high even with the combination of two or more antifungal IV-drugs. Objective: To provide a possible rescue therapy for cerebral IA refractory to conventional antifungal therapy in CGD patients. Methods: We report on the case of a 17-year-old boy affected with X-CGD, who developed chronic pulmonary aspergillosis subsequently complicated with cerebral aspergillosis refractory to multiple pharmacological strategies. The patient underwent successful extensive neurosurgical treatment consisting of endoscopic third ventriculo-cysternostomy and lesion exeresis. Histopathology studies showed within the lesion abscessual areas with micelial hyfes and positive periodic acid-shiff and Grocott staining, confirming the fungal infection. A rescue therapy with intrathecal injection of Amphotericin B at 1 mg/kg/day every 3 days for two months by external ventricular drainagewas started. Results: After 5 weeks, an improvement of the neurological signs was noted; CSF mycological cultures and detection of fungal DNA by PCR were negative. No complications related to ventricular drainage or intrathecal injection of Amphotericin B, such as nerve irritations or bacterial infections, occurred during the treatment. However, in spite of the negative mycological findings, the clincal conditions remain severely compromised. Conclusion: Intrathecal Amphotericin B in combination with systemic therapy could be a possible rescue and relatively safe treatment for selected, seriously ill patients with refractory cerebral IA and poor prognosis.