For the initial treatment of AIDS-associated cryptococcal meningitis, the use of higher-dose amphotericin B plus flucytosine is associated with an increased rate of cerebrospinal fluid sterilization and decreased mortality at two weeks, as compared with regimens used in previous studies. Although consolidation therapy with fluconazole is associated with a higher rate of cerebrospinal fluid sterilization, itraconazole may be a suitable alternative for patients unable to take fluconazole.
Incorporation of amphotericin B into liposomes significantly altered its toxicity, tissue distribution, and efficacy. Compared with intravenously administered amphotericin B-desoxycholate, liposome-amphotericin B showed a reduced acute toxicity and a maximal tolerable dose 9 times greater than amphotericin B-desoxycholate. Liposome-amphotericin B also produced higher tissue and lower serum concentrations than amphotericin B-desoxycholate, and was significantly more effective in prolonging survival of mice infected with Histoplasma capsulatum.
BMS 181184 (BMS), an analogue of pradimicin, was administered intravenously to neutropenic mice infected with either a fluconazole‐susceptible or a fluconazole‐resistant clinical isolate of Candida tropicalis. BMS prolonged survival at doses >3 mg kg−1 day−1, and at higher doses reduced tissue counts in mice. BMS was less potent mg for mg than amphotericin B. Combined BMS and amphotericin B were no more effective than either of the individual drugs.
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