Fluconazole in the management of patients with chronic mucocutaneous candidosis

SIR, The management of patients with chronic mucocutaneous candidosis (CMCC) was improved dramatically with the introduction of ketoconazole, which produced cures or remissions in a significant number of those treated.' However, relapse of the infection occurs with increasing frequency after the initial remission and this has prompted some clinicians to use continuous prophylaxis with oral ketoconazole to prevent long-term sequelae of infection, such as the development of oesophageal strictures. Although there are few confirmed reports, azole-resistant Candida albicans have been isolated from some CMCC patients on continuous ketoconazole therapy.'̂ Other patients become clinically refractory to the drug. We would like to report our experience with the new oral triazole antifungal, fluconazole, in patients with chronic mucocutaneous candidosis. The drug is currently being assessed in superficial fungal infections and has been reported to be effective in both oropharyngeal candidosis'' and cryptococcal meningitis'' in patients with AIDS. Fluconazole is well absorbed after oral administration and shows low serum binding. It can be detected in significant levels in saliva as well as in urine and cerebrospinal fiuid. It is largely eliminated via the kidneys—an unusual feature for an azole drug. Eight patients with mycologically confirmed oral candidosis of the tongue and oral mucosa were treated with fluconazole; none had received antifungal therapy for at least 6 weeks prior to treatment with fiuconazole. The seven patients had either chronic (3) or relapsing (5) oral infection associated with CMCC and had received ketoconazole as the main treatment. Those with relapsing disease had reported at least six episodes of infection within the preceding year. The chronically infected patients had been refractory, to ketoconazole prior to entering the study, but the organism had not shown resistance to ketoconazole in vitro. The mean age of these patients was 23 years (range 16-28); five had idiopathic CMCC and three the Candida endocrinopathy syndrome (hypoparathyroidism/hypoadrenalism one case and two with hypothyroidism). Each patient received 50 mg fiuconazole daily (Pfizer Central Research, U.K.) for up to 4 weeks and were assessed clinically and mycologically each week by both microscopy and culture. Clinical and mycological remissions were induced in all eight patients in a mean period of 10 days (range 7-21 days). Three patients relapsed within 4 months (mean 56 days), but all responded to a further short course of oral fiuconazole, 50 mg daily for three days. The frequency of relapse, however, was less than before and all four patients who were no longer responding to ketoconazole cleared on fiuconazole. No patient reported any adverse reactions to the drug and no abnormality of biochemical values was detected during treatment.