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Posaconazole successful in treating fluconazole- and itraconazole-resistant candidiasis
An open-label study of oral posaconazole has found that it safely and effectively treats oropharyngeal and oesophageal candidiasis in people resistant to fluconazole and/or itraconazole. The study was published in the February 15th issue of Clinical Infectious Diseases.
Mucosal candidiasis (‘thrush’) is an infection of the mouth and throat (oropharyngeal candidiasis) and/or oesophagus (oesophageal candidiasis) by the fungi Candida albicans and, more rarely, C. glabrata. Oral fluconazole is still the mainstay of antifungal treatment for mucosal candidiasis (MC). After repeated fluconazole treatment, 4 - 5% of people with advanced HIV (especially with CD4 cells counts below 100 cells/mm3) will develop fluconazole-resistant MC. Alternative treatments include itraconazole and voriconazole (which may be hampered by cross-resistance and drug interactions), and the more highly toxic intravenous drugs amphotericin B and caspofungin.
In this international, multicentre, phase III open-label clinical trial, American researchers studied oral posaconazole for the treatment of fluconazole- and/or itraconazole-resistant mucosal candidiasis. Adults with MC unresponsive to fluconazole or itraconazole treatment were enrolled between March 1998 and September 2000. A total of 199 such participants were enrolled from 30 sites (13 in the United States and 17 elsewhere): 149 had oropharyngeal candidiasis, 18 had esophageal candidiasis, and 32 had both. Most (80%) had CD4 cell counts below 100 cells/mm3
Analysis was done on a ‘modified intent-to-treat’ subset of 176 participants who had received at least one study dose of posaconazole, and had either: confirmed resistant MC at baseline, or shown no improvement after a minimum duration of prior azole therapy. In this group, 155 (88%) were men, 131 (74%) were white, and the mean CD4 cell count was 32 cells/mm3. Eighty-seven were resistant to fluconazole, ten were resistant to itraconazole, and seventy-two were resistant to both.
The original treatment protocol (‘regimen A’) consisted of 400mg oral posaconazole suspension twice daily for three days, followed by 400mg once daily for 25 days. A more intensive ‘regimen B’ (400mg twice daily for 28 days) was later added.
Of the 176 ‘modified intent-to-treat’ participants analysed, 93 (53%) responded (i.e. showed cure or improvement) after 14 days, and 132 (75%) responded after 28 days. Response rates were similar between regimens A (75.3%) and B (74.7%).
These results compare favourably to those shown in other studies for itraconazole (55% to 80%), voriconazole (83%), and caspofungin (64%). A high relapse rate of 74% was seen after 30 days off treatment; the twice-daily regimen B had a lower relapse rate (68%) than regimen A (80%). However, a long-term treatment extension “appeared to be well tolerated.”