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William G. Powderly, Dosing Amphotericin B in Cryptococcal Meningitis, Clinical Infectious Diseases, Volume 47, Issue 1, 1 July 2008, Pages 131–132, https://doi.org/10.1086/588818
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It is salutary to note that, although for the past 50 years of therapeutics, amphotericin B has been the mainstay of antifungal treatment for cryptococcal meningitis, in an era of evidence-based medicine, we remain uncertain regarding the appropriate dose of this drug to use when giving treatment to patients. The article by Bicanic et al. [1] provides some useful insight into this question, but before considering the new data, it is worth reviewing the history of amphotericin B use for treatment of cryptococcal meningitis.
Amphotericin B was available for >20 years before large, randomized trials investigating its use for systemic fungal infection were published. Cryptococcal meningitis was one of the first diseases tackled by the fledging Mycoses Study Group in the 1970s and 1980s (before the era of HIV infection and AIDS). At that time, the Mycoses Study Group's focus was on reducing the dosage and duration of use of amphotericin B as much as possible, and the findings of 2 randomized studies [2, 3] led to the conclusion that a dosage of amphotericin B deoxycholate of 0.3 mg/kg per day was effective when given in combination with flucytosine. In retrospect, the methodology of these trials, which excluded from analysis patients who died early in the course of treatment, may have led to an overly optimistic appraisal of low dosages of amphotericin B. Certainly, initial results in the treatment of AIDS-associated cryptococcal meningitis were not as encouraging.
