Fluconazole vs. amphotericin B in the treatment of candidemia – adapted from New England Journal of Medicine, November 17, 1994 – Tips from Other Journals
Systemic candidal infection, often associated with venous catheter use, has been reported to have mortality rates between 46 and 75 percent. Although amphotericin B has long been the standard treatment for systemic candidemia, this drug has many toxic side effects that complicate its use. An alternative treatment, fluconazole, a newer antifungal agent with minimal toxic effects, has been effective in treating mucosal candidiasis and esophagitis. Rex and colleagues compared amphotericin B with fluconazole in the treatment of systemic candidemia.
The study included patients who had blood cultures that were positive for Candida species, a neutrophil count greater than 500 per [mm.sup.3] (0.50 X [10.sup.9] per L) and no major immunodeficiency. Of 237 patients initially enrolled, 206 were randomized to receive either amphotericin B (0.5 mg to 0.6 mg per kg per day) or fluconazole (400 mg per day). Patients were reevaluated at two weeks, six weeks and 12 weeks after completion of therapy
Among the 103 patients treated with amphotericin B, 81 (79 percent) had successful outcomes. Treatment was considered successful if all signs and symptoms of candidal infection had resolved, if blood cultures obtained at follow-up were negative and if cultures taken from normally sterile sites that were previously positive became negative. Among the 103 patients treated with fluconazole, 72 patients (70 percent) had successful outcomes. The bloodstream infection failed to clear in 12 patients who received amphotericin and in 15 patients who received fluconazole. Candida albicans was the most common infecting species and was the organism most frequently associated with treatment failure in both groups.
At two-month follow-up, 41 patients (40 percent) in the amphotericin B group had died, compared with 34 patients (33 percent) in the fluconazole group. Thirty-seven percent of the patients treated with amphotericin B had elevations in levels of blood urea nitrogen or serum creatinine, compared with 2 percent of the patients in the fluconazole group.
The authors conclude that in the treatment of candidemia in patients without neutropenia and/or major immunodeficiency, amphotericin B and fluconazole do not differ significantly in terms of bacterial eradication. However, fluconazole is less toxic. In 149 of the patients in this study, vascular catheters were judged to be the most probable source of candidemia.
In a related editorial, Meunier suggests that fluconazole can be considered a safe alternative to amphotericin B in patients without neutropenia. However, many questions remain to be answered in such areas as the optimal management of candidemia in children, the use of oral versus intravenous routes for fluconazole treatment, the optimal duration of treatment, and the timing and necessity for removal of intravenous catheters. (New England Journal of Medicine, November 17,1994, vol. 331, pp. 1325,1371.
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