Single high dose fluconazole for oropharyngeal candidiasis
Simon Collins, HIV i-Base
Results of a randomised, double-blind, placebo controlled trial in Tanzania of single high-dose oral fluconazle was reported by Omar Hamza and colleagues from Muhimbili University, Tanzania.
The trial randomised 220 HIV-positive patients with clinical and mycological evidence of oropharyngeal candidiasis to receive oral fluconazole doses of either 750-mg single dose or standard dose of 150 mg once-daily for 2 weeks. Each arm included 110 patients.
Results were similar in each group and are detailed in Table 1. There were no statistically significant differences between the two groups. Approximately 95% patients were clinically cured (OR, 0.825; 95% CI, 0.244-2.789; p=0.99) and 85-75% mycologically cured (OR, 1.780; 95% CI, 0.906-3.496; p=0.129).
Table 1: Results from single dose vs 2-week fluconazole
|750mg single dose||14-day 150mg dose|
|Clinical cure||104 pts (94.5%)||105 pts (95.5%)|
|Clinical improvement||2 pts (1.8%)||4 pts (3.6%)|
|Treatment failure||4 pts (3.6%)||1 (0.9%)|
|Mycological cure||93 pts (84.5%)||83 pts (75.5%)|
|Mycological failure||17 pts (15.5%)||27 pts (24.5%)|
Overall, clinical cure was not achieved in 11 patients and for all of them, Candida species were isolated from patient specimens at baseline and on day 14. In 33 patients (15.0%), clinical cure was obtained despite persistent positive culture results on day 14 (mycological failure).
No differences were observed in relapse rates (OR, 1.073; 95% CI, 0.456-2.523; P=0.99). The average time to relapse after clinical cure was 18-20 days. Twenty-two (91.7%) of 24 patients who experienced relapse during follow-up had CD4 cell counts <200 cells/mm3, 16 (66.7%) had CD4 cell counts <100 cells/mm3, 17 (70.8%) were not receiving HAART, and 14 (58.3%) had had previous episodes of OPC.
The mean plasma fluconazole concentrations on days 1, 4 or 5, 7, and 14 in the 14-day fluconazole group were 13.35, 5.46, 1.37, and 0.32 mg/L and 4.18, 6.88, 7.94, and 7.62 mg/L, for the single-dose and 14-day groups respectively. These differences were statistically significant for days 1, 7 and 14.
Overall, adverse events were mild, and no differences in frequency of adverse events were noted between patients in the 2 treatment regimens. Because most of the study patients were in an advanced stage of HIV infection and AIDS, abnormalities in full blood count and liver function tests were common.
In this study, the mycological cure rate, with a single-dose treatment of 750 mg fluconazole, was much higher (84.5%) than the 6%-41% mycological cure rates reported from studies using 150mg single dose treatment.
The authors concluded “The use of a single high dose of fluconazole … presents the advantages of simplicity and convenience, thus improving compliance and reducing the cost of therapy. A single dose of five 150-mg tablets is less costly than fourteen 150-mg tablets taken over a 14-day course and, therefore, could be used, especially in resource-limited settings like in sub-Saharan Africa. In addition, administration of the single-dose therapy can be observed directly by medical personnel, thereby assuring patient compliance.”
Omar J et al. Single-Dose Fluconazole versus Standard 2-Week Therapy for Oropharyngeal Candidiasis in HIV-Infected Patients: A Randomized, Double-Blind, Double-Dummy Trial. Clinical Infectious Diseases 15 November 2008, Vol. 47, No. 10: 1270-1276.