Central nervous system aspergillosis in an immunocompetent patient: Cure in a hospice setting with very high-dose itraconazole

Abstract

Aspergillosis of the central nervous system (CNS) is a rare condition with exceedingly high mortality. This study describes the case of an immunocompetent 42-year-old man with a history of intravenous drug use and hepatitis C who developed multiple Aspergillus lesions in the cerebellum. Despite neurosurgery and antifungal therapy with amphotericin B, he had a protracted hospital course with multiple complications, eventually developing cognitive and motor impairment due to progressive cerebellar lesions. After transfer to hospice and palliative care service, oral itraconazole was escalated to 1600 mg/day with the hope of palliating headache, nausea, and cognitive impairment. Remarkably, the patient stabilized and improved over time. After 14 months, this unprecedented high-dose regimen was discontinued, and the patient was discharged home with only mild cerebellar motor impairment.

Cerebral Vasculitis Caused by Aspergillus Simulating Ischemic Stroke in an Immunocompetent Patient

“…The cases described as being "immunocompetent" actually present factors that are traditionally associated with the cerebral form of the disease (postoperative neurosurgical patients), chronic otorhinolaryngological disease (sinusitis, otitis, or mastoiditis), or diseases that are not officially categorized as immunosuppressive, but that are associated with invasive infections by fungi (diabetes mellitus, use of illicit injectable drugs, and hepatitis C) (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

The biocontaminants and complexity of damp indoor spaces: more than what meets the eyes

“…CNS complications in one person involved headache, nausea, motor impairment and cognitive decline due to progressive cerebellar lesions. After treatment with high doses of itraconazole (1600 mg/day), the patient recovered with only mild cerebellar motor impairment (Palanisamy et al, 2005).…”

CNS infections in patients with hematological disorders (including allogeneic stem-cell transplantation)—Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)

“… Primary anti-infective treatment b - to cure - Voriconazole (i.v., 6 mg/kg q12h for the first 24 h, then 4 mg/kg q12h) AII u [ 117 , 118 ] -To obtain material for diagnosis L-AmB (i.v., ≥5 mg/kg/day, optimal dose unclear) or ABLC c (i.v., 5 mg/kg/day) BIII Reserved for rare cases (e.g. severe intolerance to voriconazole, resistant isolates), might in particular be useful if mucormycosis cannot be excluded [ 119 – 126 ] -To prevent serious neurological sequelae, decrease the burden of infected tissue and improve outcome Itraconazole DIII Higher doses (800 mg/day) might be beneficial, low CNS penetration [ 127 – 129 ] Caspofungin, micafungin DIII Few clinical data [ 130 , 131 ] Posaconazole DIII [ 132 , 133 ] D-AmB DII u Unfavorable toxicity profile, low efficacy [ 134 , 135 ] Stereotactic or open craniotomy for biopsy, abscess drainage or excision of lesions BII u Resection might be effective in particular in patients with a focal lesion, a combined neuro- and rhinosurgical approach is recommended in selected cases [ 117 – 119 , ...…”

“…Amphotericin B deoxycholate (D-AmB) should be avoided due to its poor tolerability and negligible efficacy [ DII u ], but the use of higher doses of liposomal AmB (L-AmB) resulted in successful outcomes in a limited number of patients [ BIII ] [ 119 – 123 , 134 ]. Due to its limited CNS penetration and the limited number of successfully treated cases in the literature, the use of itraconazole does not appear justifiable in patients with CNS aspergillosis [ DIII ] [ 127 – 129 ]. Posaconazole has been used in a series of patients with CNS infections caused by various fungi, including three assessable patients with CNS aspergillosis [ DIII ] [ 132 ].…”