Long-term Itraconazole Therapy Research Articles

An Unusual Cutaneous Tumor: African Histoplasmosis following Mudbaths: Case Report and Review

African histoplasmosis, caused by Histoplasma capsulatum var. duboisii, is endemic in Africa. The disease usually involves the skin, subcutaneous tissue, and bones. A case of African histoplasmosis presenting as a cutaneous tumor and non-healing wound in a 66-year-old immunocompetent male residing in Africa, the first ever reported following mudbaths and acupuncture, is hereby reported. Diagnosis was confirmed by means of polymerase chain reaction performed on tissue material. The patient was started on long-term itraconazole therapy and he responded well. African histoplasmosis should be included in the differential diagnosis of non-healing wounds or tumor-like lesions, especially in the context of mudbaths in an endemic area.

Invasive aspergillosis of the temporal bone

Invasive aspergillosis of temporal bone, an extremely rare yet potentially life-threatening disease entity, occurs mostly in immuno-compromised individuals. We report a case of a 65-year-old diabetic male who presented with bilateral ear discharge, bilateral subepithelial ear masses, and progressive left facial palsy of recent onset. The biopsy specimen taken from either side after surgical debridement revealed only nonspecific inflammatory granulation tissue, but the culture of the tissue was positive for Aspergillus flavus. Invasive aspergillosis was confirmed by demonstration of the fungi in the tissues with Gomori-Methanamine Silver staining. The patient was hence put on long-term Itraconazole therapy and is presently doing well. The possibility of invasive fungal otitis always needs to be considered as a differential diagnosis in immuno-compromised patients presenting with atypical otomastoiditis so as to diagnose this rare condition at an early stage to reduce the delay in the treatment and prevent its possible complications such as skull base osteomyelitis and progressive cranial nerve palsies.

In Vitro Acquisition of Secondary Azole Resistance in Aspergillus fumigatus Isolates after Prolonged Exposure to Itraconazole: Presence of Heteroresistant Populations

Secondary resistance to azoles in Aspergillus fumigatus isolates from patients taking long-term itraconazole therapy has been described. We studied the acquisition of secondary azole resistance in 20 A. fumigatus isolates with no mutations at codon 54, 98, 138, 220, 432, or 448 in the cyp51A gene. Adjusted conidium inocula (3 × 10(7) CFU/ml) of each isolate were prepared and progressively or directly exposed to increasing itraconazole concentrations, ranging from 0.5 μg/ml to 16 μg/ml. Itraconazole, voriconazole, and posaconazole MICs were determined using the CLSI M38-A2 procedure before (MIC(initial)) and after (MIC(final)) exposure to itraconazole. In both procedures, the MIC(final) was significantly higher than the MIC(initial). However, after progressive exposure to itraconazole, the MICs of the three azoles were higher than after direct exposure. No mutations were found at codon 54, 98, 138, 220, 432, or 448 in the cyp51A gene of isolates growing at the highest concentration of itraconazole. More concentrated conidium inocula (2 × 10(9) CFU/ml) plated in itraconazole at 4 μg/ml revealed the presence of heteroresistant populations in two initially wild-type isolates. These isolates became resistant to itraconazole and posaconazole only after use of the concentrated inoculum. These heteroresistant isolates harbored a mutation at codon G54, and the MICs of itraconazole and posaconazole were >16 μg/ml. In all procedures, A. fumigatus short tandem repeat (STRAf) typing was used to demonstrate that the genotype did not change before or after exposure to itraconazole.

An apple-core lesion in the colon: An infectious etiology

Gastrointestinal involvement occurs in about 70% to 90% of histoplasmosis cases but is usually not the initial manifestation. We present the case of a 52-yearold HIV-positive woman who presented with gastrointestinal symptoms and an apple-core lesion on CT scan of the abdomen. The patient had been diagnosed with histoplasma colitis eight months earlier and was started on long-term itraconazole therapy. However, she prematurely discontinued treatment. A colonoscopy during the present hospitalization revealed a 3.5-cm mass, biopsies of which revealed Histoplasma capsulatum. In the present report, we discuss the differential diagnosis of apple-core lesions in the colon and the importance of keeping histoplasmosis on the differential diagnosis, especially in endemic areas like the Ohio River valley. It is equally important to ensure compliance with treatment of histoplasmosis, as well as close follow-up, as progression to colonic obstruction while on medical management has been reported.

Improvement with long-term itraconazole therapy forFonsecaea pedrosoi-related mediastinal phaeohyphomycosis: Fig. 1—

To the Editors: In the September 2006 issue of the European Respiratory Journal , we reported the first culture-proven case of mediastinal mass due to Fonsecaea pedrosoi that had been successfully managed medically 1. Maintenance therapy with oral itraconazole 100 mg b.i.d. was continued for a total of 3 yrs. This decision was taken in view of …

Adrenal response to corticotrophin and testosterone during long-term therapy with itraconazole in patients with chromoblastomycosis

In order to establish whether long-term itraconazole therapy can affect adrenal or testicular function, the adrenal response to corticotrophin and testosterone was evaluated by radioimmunoassay in 15 patients undergoing treatment for chromoblastomycosis. Mean cortisol and testosterone concentrations were 12.4 microg/dL and 454 ng/dL respectively at baseline and 15.4 microg/dL and 480 ng/dL respectively after 12.4+/-5.2 months of treatment with itraconazole (200-400 mg daily). Results were analysed using Student's t-test. There was no clinical or laboratory evidence of steroidogenic or androgenic impairment.

Treatment of chromoblastomycosis with itraconazole.

The results of long-term itraconazole therapy in 10 patients with active chromoblastomycosis due to F. pedrosoi were reported. Therapy consisted of 100 or 200 mg/day of itraconazole, the length of therapy depending on the patient's response (12 to 24 months). This new triazole proved effective in reducing the number, size, and severity of the lesions in nine of the patients. Those patients with minor involvement profited more from therapy and were cured; patients with moderate involvement achieved either minor or major improvement. In most cases, signs and symptoms began to improve after 6 months of therapy. Mycological tests (in which tissue samples were treated with potassium hydroxide and cultured) became negative in six patients, but the fungus was eradicated in only three patients. Itraconazole produced no side effects. In spite of the need for long-term therapy, this new azole derivative effectively controls the disease.