Itraconazole cyclodextrin solution for fluconazole-refractory oropharyngeal candidiasis in AIDS: correlation of clinical response with in vitro susceptibility.
Phillips, Peter *,+; Zemcov, Janet ++; Mahmood, Wafeeq *,+; Montaner, Julio S.G. *; Craib, Kevin *; Clarke, Alison M. ++
10(12):1369-1376, October 1996.
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.
(C) Lippincott-Raven Publishers.