Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
Treatment of HIV-related fluconazole-resistant oral candidosis with D0870, a new triazole antifungal.
AIDS. 1998 Mar 5;12(4):411-6. Unique Identifier : AIDSLINE MED/98178993 Cartledge JD; Denning DW; Dupont B; Clumeck N; De Wit S; Midgley J; Hawkins DA; Gazzard BG; Chelsea and Westminster Hospital, London, UK.
Abstract:
OBJECTIVES: To evaluate the efficacy and tolerance of D0870 in the treatment of HIV-related fluconazole-resistant oro-oesophageal candidosis. DESIGN: Multicentre open study. PATIENTS: HIV-seropositive patients with oro-oesophageal candidosis despite at least 7 days of treatment with fluconazole at doses of 100 mg per day or more. METHODS: Patients received an initial dose of D0870 (150 mg), then 25 mg per day for 6 days. Symptoms and signs of candidosis were compared at entry and on days 3 and 7 of treatment. At each visit, samples were taken for safety monitoring and for in vitro susceptibility testing of Candida isolates. Limited pharmacokinetic samples were taken on days 1 and 7. RESULTS: Of 26 evaluable patients, 16 showed partial improvement, nine showed no improvement, and only one had full clearance of thrush by day 7. In vitro testing of the cleared patient's isolate suggested that it was susceptible to fluconazole. Symptoms of dysphagia cleared in 14 and improved in five of the 22 patients with presumptive oesophageal involvement at entry. Pharmacokinetic measurement showed wide variability in maximum D0870 levels recorded on day 1 (range, 0.07-0.34 mg/l) and susceptibility testing of isolates also showed a range of minimal inhibitory concentration values to D0870 (range, < 0.06-8 mg/l; median, 0.25 mg/l). When these data were combined with clinical response there was a strong suggestion that lack of symptomatic improvement was related to low plasma D0870 levels or to the presence of less D0870-susceptible isolates. Six patients were noted to have a fall in haemoglobin, three of whom were receiving concomitant therapy known to suppress bone marrow. Three patients reported headaches as adverse events that were attributed to study medication, but D0870 was well tolerated overall. CONCLUSIONS: D0870 shows promise in the treatment of fluconazole-resistant oro-oesophageal candidosis and was well tolerated, although efficacy in this difficult-to-treat patient group was probably limited due to the inadequate plasma levels achieved in this pilot study with the low doses of D0870 administered.
Keywords: *Antifungal Agents/THERAPEUTIC USE *AIDS-Related Opportunistic Infections/DRUG THERAPY *Candidiasis, Oral/DRUG THERAPY *Fluconazole/PHARMACOLOGY *Triazoles/THERAPEUTIC USE
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Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
