A randomized trial of continuous or intermittent therapy with fluconazole for oropharyngeal candidiasis in HIV-infected patients: Clinical outcomes and development of fluconazole resistance

Sanjay G. Revankar, William R. Kirkpatrick, Robert K. McAtee, Olga P. Dib, Annette W. Fothergill, Spencer W. Redding, Michael G. Rinaldi, Susan G. Hilsenbeck, Thomas F. Patterson

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

PURPOSE: The effects of continuous or intermittent therapy with fluconazole on the recurrence of and the development of fluconazole resistance are not known. PATIENTS AND METHODS: We studied human immunodeficiency virus (HIV)-positive patients with CD4 cell count <350 X 106/L and oropharyngeal candidiasis in a prospective, randomized study. After initial treatment, 20 patients (16 of whom completed 3 months of follow-up) received continuous fluconazole at 200 mg/day, and 48 patients (28 of whom completed follow-up) received intermittent therapy at the time of symptomatic relapses. Oral samples were obtained weekly during episodes of infection and quarterly as surveillance cultures. Development of resistance was defined as a fourfold rise in minimum inhibitory concentration (MIC) to at least 16 μg/mL from the initial culture in the same species, the emergence of new, resistant (MIC ≤ 16 μg/mL) species, or a significant increase in the proportion of resistant isolates. RESULTS: During a mean follow-up of 11 months, median annual relapse rates were lower in patients on continuous therapy (0 episodes/year) than in patients on intermittent therapy (4.1 episodes/year; P<0.001). Sterile cultures were seen in 6 of 16 (38%) patients on continuous therapy compared with 3 of 28 (11%) on intermittent therapy (P = 0.04). Microbiological resistance developed in 9 of 16 (56%) patients on continuous treatment, compared with 13 of 28 (46%) on intermittent treatment (P = 0.75). However, despite isolates with increaSed MICs, 42 of 44 patients responded to fluconazole in doses up to 800 mg/day. CONCLUSIONS: In patients with frequent recurrences, continuous suppressive therapy significantly reduced relapses and colonization. Resistance occurred with both continuous and intermittent therapy; however, therapeutic responses were excellent.

Original languageEnglish (US)
Pages (from-to)7-11
Number of pages5
JournalAmerican Journal of Medicine
Volume105
Issue number1
DOIs
StatePublished - Jul 1 1998

ASJC Scopus subject areas

  • Medicine(all)

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