DOUBLE-BLIND RANDOMIZED STUDY OF THE EFFECT OF INFUSION RATES ON TOXICITY OF AMPHOTERICIN-B

Results of a double-blind randomized non-crossover study of rapid (45 min) versus slow (4 h) infusion of amphotericin B administered to 20 patients with proven or suspected fungal infection are reported. Toxicity was higher in the rapid infusion group than it was in the slow infusion group (mean total 7-day chill score, 173 +/- 276 versus 20 +/- 30 [P < 0.01]; mean total 7-day dosage of meperidine required to abate rigors, 180 +/- 133 versus 58 +/- 78 mg [P < 0.05]; and mean maximum total 7-day pulse rise, 225 +/- 64 versus 135 +/- 56 beats per min [P < 0.02], respectively). When analyzed on a daily basis, the mean chill score, meperidine dosage, and pulse rise were also higher; and in addition, nausea and vomiting (5 of 11 patients who received a rapid infusion versus 0 of 9 patients who received a slow infusion [P < 0.01]) appeared to be more common in those who received amphotericin B rapidly. The daily analysis approach proved that tolerance to these side effects developed with each subsequent infusion day, and by day 7 the incidence and severity were the same. This development of tolerance was significant for the mean chill score in the rapid infusion group (P < 0.05) and for the proportion of patients with chills (P < 0.005 for the slow infusion group; P < 0.05 for the rapid infusion group). A decrease in creatinine clearance to > 51% of the baseline value was seen in two patients in each group. There were five deaths (four in the rapid infusion group, 1 in the slow infusion group) within 1 month, but none was clearly related to the amphotericin B infusion. The mean time to defervescence was similar for each group (10.8 +/- 4.1 days in the slow infusion group versus 9.9 +/- 5 days in the rapid infusion group). A rapid infusion regimen for amphotericin B cannot be recommended, at least during the first 5 to 7 days of treatment.