Patients with haematological malignancies requiring an antifungal therapy were randomly assigned to receive amphotericin B diluted in either 5% dextrose or in fat emulsion (Intralipid). Twenty-one patients were included in each group. Mean duration of amphotericin B therapy was 8.4 days in the dextrose group and 12.8 days in the Intralipid group. Amphotericin B infusion induced chills in 16 of 21 patients in the dextrose group and in 5 of 21 in the Intralipid group (P = 0.0008). Serum creatinine increased > 75% from baseline in ten patients in the dextrose group compared with only two in the Intralipid group (P = 0.007). A > or = 50% decrease of creatinine clearance was observed in 14 of 21 patients in the dextrose group compared with seven of 21 patients in the Intralipid group (P = 0.025). No difference was found between the two groups with regard to potassium and sodium requirement. Among patients who did not receive magnesium before antifungal therapy, magnesium supplementation was required more frequently in the dextrose group (8/12 vs 2/11; P = 0.02). Concomitant amikacin dosage reduction was more frequent in the dextrose group due to nephrotoxicity (7/19 vs 2/20; P = 0.045). A similar difference in vancomycin dosage reduction was observed between the two groups (12/20 vs 5/19; P = 0.03).
The efficacy and tolerance of a new amphotericin B lipid emulsion (AmB-IL) in which amphotericin B was diluted in a lipid solution for parenteral nutrition (Intralipid) was assessed in fourteen episodes of candidaemia occurring in neutropenic patients. The strains isolated were Candida krusei (nine cases), Candida albicans (three cases), Candida parapsilosis (one case) and Candida lusitaniae (one case). An AmB-IL was administered at a mean dosage of 1.18 mg/kg/day (range 0.73-1.55) for 22 days (range 6-62). Flucytosine was added to AmB-IL in 12 patients (mean duration 10.6 days). Chills were noted in only 3/306 infusions of AmB-IL. A mild increase of serum creatinine level from 9.3 +/- 3 mg/L (baseline) to 10.9 +/- 3 mg/L (after completion of AmB-IL) and mild decrease of creatinine clearance from 83 +/- 28 mL/min to 56 +/- 21 mL/min were observed. These changes did not correlate with either daily or total dose of AmB-IL or length of therapy. Seven patients were cured and six improved (patients who subsequently died due to nonfungal cause) with AmB-IL. One patient died due to C. krusei pneumonia. In conclusion AmB-IL is a well-tolerated method of amphotericin B administration. It could facilitate the use of amphotericin B without impairing its efficacy for the treatment of candidaemia in neutropenic patients.
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