Itraconazole cyclodextrin solution for fluconazole-refractory oropharyngeal candidiasis in AIDS: Correlation of clinical response with in vitro susceptibility

1996 | AIDS

http://www.ncbi.nlm.nih.gov/pubmed/8902066

Abstract:

OBJECTIVE: To evaluate the efficacy of itraconazole cyclodextrin solution in fluconazole-refractory oropharyngeal candidiasis (OPC), and to correlate clinical outcome with in vitro susceptibility and serum azole levels. DESIGN: A prospective, open-label, intervention study. SETTING: A university hospital, which serves as the provincial HIV referral center. PATIENTS AND INTERVENTIONS: Thirty six HIV-infected individuals referred for fluconazole-refractory OPC were evaluated prospectively between May 1993 and March 1995, including clinical assessment, serum azole levels, and susceptibility testing of Candida spp, isolates. Itraconazole solution was administered orally at a daily dose of 200 mg for 14 days, followed by suppressive therapy. Thirty-four patients were evaluable. MAIN OUTCOME MEASURE: Resolution of oral pseudomembranous lesions. RESULTS: Initial isolates were Candida albicans (n = 33), C. glabrata (n = 1), C. krusei (n = 1), and mixed infection with C. albicans and C. krusei (n = 1). Fluconazole serum levels obtained at the time of failed therapy ranged from 4.7 to 40 mg/l (median, 12.9 mg/l). Itraconazole was generally well tolerated. Clinical responses were observed in 65% (22 out of 34) of evaluable cases. Among the responders, relapse had occurred within 2 months for four (36%) out of 11 cases who continued with follow-up. The median fluconazole minimal inhibitory concentration (MIC) was 64 mg/l for isolates from fluconazole-refractory cases, compared with a median of 0.5 mg/l for control isolates (P = 0.002). The median itraconazole MIC for isolates from fluconazole-refractory cases was 1.25 mg/l, compared with a median of 0.078 mg/l for controls (P = 0.011). CONCLUSION: A correlation between clinical response and in vitro susceptibility was clearly demonstrated for fluconazole, but not for itraconazole. Itraconazole cyclodextrin solution may be effective for fluconazole-refractory OPC and should be considered prior to salvage therapy with intravenous amphotericin B.

BC Centre for Excellence in HIV/AIDS

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Itraconazole cyclodextrin solution for fluconazole-refractory oropharyngeal candidiasis in AIDS: Correlation of clinical response with in vitro susceptibility

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