Therapeutic failures with miconazole

A retrospective review of therapeutic failures of miconazole in three patients is presented. Miconazole, a new imidazole derivative, is a broad-spectrum antifungal agent purportedly effective topically, orally, and parenterally against a number of species of fungi. Three patients with the following culturally proven deep fungal infections were treated with miconazole: (i) destructive arthritis (Sporothrix schenckii), (ii) meningoencephalitis (Cryptococcus neoformans), and (iii) disseminated aspergillosis (Aspergillus fumigatus). All the organisms were susceptible in vitro to 1.56 mug or less of miconazole per ml using a broth dilution technique. In each patient, miconazole administered intravenously in dosages of 30 mg/kg per day failed to control or eradicate infection. Miconazole serum levels ranged from <0.5 to 4.35 mug/ml as determined by radial diffusion bioassay. Cerebrospinal fluid levels were virtually undetectable. In one patient (C. neoformans), miconazole was given intraventricularly in doses of 15 mg without response. Therapeutic failures were attributed to suboptimal body fluid levels of miconazole. The reason(s) for such low levels of activity was not clear, but may have been poor penetrance into tissues, in vitro inactivation, and/or unusually rapid excretion. Untoward reactions from miconazole included fever, chills, nausea, vomiting, and phlebitis.