Successful Treatment of Cerebral Aspergillosis with a High Oral Dose of Itraconazole after Excisional Surgery.

Abstract

Wereport a case of cerebral aspergillosis which originated from the sphenoid sinus, and involved a progressive decrease of visual acuity. The neurological signs indicated a cavernous sinus invasion. After extensive intracranial surgery we treated the residual aspergillosis with a high oral dose of itraconazole (800 mg/d for 4 months, followed by 400 mg/d for 5 months). The neurological impairments of the patient gradually subsided with the resolution of the fungal lesion shown on MRI. The successful therapy indicated that itraconazole has a significant role in the treatment of advanced cerebral aspergillosis if it is used in high doses (16 mg/kg/d for adults).( Internal Medicine 38: 829-832, 1999)

Itraconazole exerts its anti-melanoma effect by suppressing Hedgehog, Wnt, and PI3K/mTOR signaling pathways

“…Thus, rational combination of this compound with other chemo drugs that may target some specific tumorigenic mechanism will be an effective strategy to enhance conventional cancer therapy. The response doses of itraconazole in mice examined in this experiment are indeed higher than the commonly used therapeutic doses (i.e., 400 mg/day orally for 15 days) in patients with fungal infections, but are similar to itraconazole doses in patients with severe fungal infections [60, 61], In these cases, a high dose of itraconazole ranging from 600 to 900 mg/day can be given to patients for 3 to 16 months with close monitoring for any toxicity of this compound. With high dose itraconazole in our mice model (75 and 100 mg/kg), we find no signs of severe liver and kidney damage except a slight elevation of serum cholesterol during the 20 days of treatment.…”

Tremor: a newly described adverse event with long-term itraconazole therapy

“…Tremor has been reported with newer triazoles,3 13 but only one previous case with high-dose itraconazole (800 mg/day) has been described 14. Furthermore, three of our patients had itraconazole levels exceeding 15 mg/l, suggesting a potential toxicity–exposure relationship; however, while such a relationship is theoretically probable, there is currently little empirical evidence to support this.…”

Central nervous system Aspergillus fumigatus infection after near drowning

“…Amphotericin B and other clinical and surgical alternatives showed few encouraging results. [15][16][17] Although intravenous amphotericin B has been the mainstay treatment for CNS aspergillosis, two new drugs for IV usevoriconazole and caspofungin-are promising agents, with a good tolerability profile. [18][19][20][21][22] Pseudallescheria boydii CNS infections have been described after near drowning in dirty and polluted waters or in manure reservoirs.…”