New antifungal provides new treatment option for oesophageal candidiasis

A new antifungal drug called micafungin (Mycamine) is just as effective as fluconazole in the treatment of oesophageal candidiasis in HV-positive people, according to findings from a randomised, double-blind study published in the September 15^th edition of Clinical Infectious Diseases.

The study randomised 245 HIV-positive patients with oesophageal candidiasis to receive either fluconazole (200mg per day) or one of three micafungin doses (50, 100 or 150mg per day) by intravenous infusion for 14-21 days.

Patients were excluded from the study if they were known to be infected with a fluconazole-resistant strain of Candida. Patients were recruited at sites in Peru, South Africa and Brazil, reflecting the rarity of oesophageal candiasis in North America and Europe since the introduction of highly active antiretroviral therapy (HAART).

The primary endpoint in the study was the proportion of patients who showed complete disappearance of candidal plaques on an oesophageal endoscopy, with secondary endpoints of cure rate at day 14, incidence of relapse, clinical response and fungal cultures negative for Candida.

Forty-six patients were excluded from the final analysis because they missed endoscopies at the end of treatment or failed to take at least ten doses of the study drug. In addition 36 patients discontinued treatment, with no apparent bias towards a particular dose or drug.

By intent to treat analysis, candida clearance rates were 68.8%, 77.4% and 89.9% for the 50, 100 and 150mg micafungin doses, compared to 86.7% of the fluconazole group, and there was no statistically significant difference by intent to treat analysis. However an on treatment analysis showed a higher cure rate in patients treated with micafungin 150mg compared to fluconazole (100% vs 77.8%) in patients with grade 3 candidiasis at baseline (evidence of ulcerated candidiasis by endoscopy).

The improvement in candidiasis as measured by endoscopy was dose-related in the micafungin groups, and severity of oesophageal candidiasis as measured by reported symptoms and ability to drink water improved rapidly after beginning treatment. Within three days at least half of patients reported a reduction in the severity of their symptoms and after seven days 75% reported improvements. There was no difference in the speed of improvement between the higher dose micafugin groups and the fluconazole group.

Fungal clearance as measured by culture was higher in patients treated with micafungin 100mg than 150mg (p = 0.031), but did not differ significantly between either dose and the fluconazole arm.

Fever, abdominal pain, nausea, diarrhoea, leukopenia, injection site reactions and headache were reported frequently in all treatment groups, but a higher frequency of unspecified renal adverse events was seen in micafungin-treated patients (3.8% vs 0%), although none resulted in treatment discontinuations.

Micafungin is one of a new class of antifungals called echinocandins. Another echinocandin, caspofungin, has been shown to interact with nevirapine and efavirenz. In this study 41 patients received either drug, but no interaction with micafungin could be detected, and another drug interaction study looking at the effects of the TB drugs rifampicin and rifabutin on micafungin levels found no negative effect, suggesting that it may have fewer drug interaction problems than other antifungals.

Manufactured by Fujisawa, micafungin is not yet approved in the European Union or the United States, and the company announced last week that European drug regulators have asked for additional information before the product can be approved. Micafungin may not be available in Europe until 2006, a company spokesperson said.