Amphotericin B in a lipid emulsion for the treatment of cryptococcal meningitis in AIDS patients

Abstract

We determined the safety and efficacy of deoxycholate-amphotericin B (d-AmB) mixed with Intralipid (IL) as the initial treatment of AIDS-associated cryptococcal meningitis in a phase II, multicentre, non-comparative open study, assessing two dosages of ILd-AmB: 1 mg/kg (group A, n = 9) and 1.5 mg/kg (group B, n = 6). Patients were treated daily for 2 weeks, then three times weekly for 4 weeks. The ILd-AmB dosage was decreased due to toxicity in three patients in each group. Serum creatinine increased significantly on day 14 in group A and on day 7 in group B. Nephrotoxicity, (serum creatinine level > 165 mumol/L) was noted in two and five patients in groups A and B, respectively. Nine adverse haematological events were noted (seven cases of anaemia requiring transfusion, and two cases of neutropenia < 750/mm). Two patients had an increase in serum alkaline phosphatase. In each cohort, 15% of the infusions were associated with fever and/or chills. Successful outcome was obtained in half of the patients. We conclude that, in AIDS patients with cryptococcosis, tolerance to ILd-AmB was acceptable when the daily dosage did not exceed 1 mg/kg, but the higher 1.5 mg/kg daily dosage was associated with an unacceptable rate of nephrotoxicity. Neither of these relatively high daily dosages of ILd-AmB achieved an improved rate of successful outcomes compared with lower daily dosages of conventional d-AmB in glucose.