Refractory Mucosal Candidiasis in Advanced HIV Infection [CJ Fichtenbaum, et al. CID 2000;30:749]: This is ACTG study 816, which was a prospective, observational study of fluconazole-refractory candidiasis in patients with advanced HIV infection, defined as a CD4 count <50/mm³. Fluconazole-refractory mucosal candidiasis was defined as candidiasis, primarily thrush, that failed to respond despite 14 days of treatment with fluconazole in doses of at least 200 mg/day. There were 842 patients with a median CD4 cell count of 14/mm³ enrolled at 25 ACTG study sites. There were 36 (4.3%) patients with refractory candidiasis, for an incidence of 4.2/100 person years. Multivariate analysis showed that the risks for these fluconazole-refractory cases were daily or every-other-day use of fluconazole (odds ratio = 5.6; p = 0.004) and the use of TMP-SMX within the past six months (odds ratio = 2.4; p = 0.04). Cultures were obtained from 29 of the 36 patients at the time of failure, and C. albicans was recovered from 28 (97%). In vitro susceptibility tests showed that 18 (69%) of these isolates were resistant to fluconazole at 64 mcg/ml, and 1 (4%) had a MIC <8 mcg/ml.
Comment: This study showed results that are not surprising in terms of the risk for fluconazole-resistant thrush. The implication is that fluconazole should be used episodically; the notable exception is for maintenance treatment of cryptococcosis. The authors note that the incidence of fluconazole-refractory esophagitis and vaginitis appears to be much lower. Other studies have shown that low CD4 cell counts represent an independent risk; this factor could not be studied in this trial because the enrollment criteria restricted analysis to patients with CD4 cell counts of <50/mm³. The study was done before widespread use of HAART (1994 - 96) so that the impact of potent antiretroviral treatment, which is expected to be substantial, could not be assessed. posted 6/29/2000