Correlation of predominance of fluconazole-resistant isolates and response to therapy in recurrent oropharyngeal candidiasis in HIV-infected patients

Development of fluconazole resistance has been seen with increasing frequency in the setting of oropharyngeal candidiasis (OPC) in HIV-infected patients. Correlation of microbiological and clinical resistance has been demonstrated and is predicted by susceptibility testing using the NCCLS method. Dose-dependent susceptibility occurs, and the presence of resistant isolates in culture does not necessarily imply clinical resistance. Fifty-nine HIV+ patients with a mean CD4<50 (range 3-318) presenting with signs and symptoms of OPC were enrolled in a longitudinal study of OPC. Cultures were taken weekly until clinical resolution using oral saline swish and swab samples. Therapy consisted of fluconazole tabs 200 mg on the first day and 100 mg for six days and was continued until resolution of symptoms and oral lesions. Fluconazole was increased on a weekly basis as clinically required to a maximum dose of 800 mg/day. Serial dilutions of oral rinses were plated onto a novel chromogenic agar containing fluconazole to detect fluconazole resistant yeasts and non-albicans species. Percent resistance was calculated by determining growth on agar with and without fluconazole. From this cohort, 4 patients (mean follow-up 12 mo., range 8-17) with recurrent OPC who developed microbiological and clinical resistance requiring increasing doses of fluconazole were selected for further study. None had baseline isolates with MICs ≥16 μg/ml and all had resistant isolates detected with recurrent episodes. The proportion of resistant isolates correlated well with clinical resistance (i.e. requiring > 200 mg/day fluconazole for clinical resolution of OPC): 1/14 episodes with 0% resistant isolates required > 200 mg/day fluconazole for clinical resolution, compared with 3/5 with 1-50% resistance, and 10/11 with > 50% resistance. The percentage of resistant isolates in an episode of OPC as determined by agar dilution screening appears to correlate with clinical resistance. Use of screening susceptibility testing may be useful in the management of recurrent OPC.