Amphotericin B toxicity reduced by administration in fat emulsion

OBJECTIVE: To report a patient with intolerance to amphotericin B reversed by preparing the antifungal in fat emulsion 20% and to review the medical literature on innovative formulations of amphotericin B. CASE SUMMARY: A 51-year-old man diagnosed with acute myelogenous leukemia was treated with standard induction chemotherapy. Empiric antibiotic therapy was initiated 2 days postchemotherapy; however, the patient continued to be febrile until day 7. At this time amphotericin B 35 mg/250 mL D5W over 4 hours was administered. Despite premedication, the patient experienced severe rigors, chills, and fever. As the result of continuing infusion-related adverse events, the patient refused further therapy after the third daily dose. In an attempt to reduce the infusion-related events, a trial of amphotericin B 35 mg/35 mL of fat emulsion 20% was administered over 2 hours after patient consent was obtained. Premedication was administered and the patient tolerated therapy without adverse events. Amphotericin B dosage escalations to 50 and 70 mg were tolerated similarly. During this treatment the patient became afebrile and the serum creatinine concentration decreased to normal. DISCUSSION: Despite significant toxicities and the development of newer antifungal agents, amphotericin B remains the drug of choice for the empiric coverage of suspected fungal infection in neutropenic patients. Amphotericin B often exacerbates the nephrotoxicity of other agents characteristically prescribed in these patients. Furthermore, infusion-related events, if not intolerable, can dramatically reduce the patient's quality of life. For these reasons, novel means of amphotericin B administration are being explored. CONCLUSIONS: The delivery of amphotericin B in a lipid diluent may have substantial benefit in reducing the nephrotoxicity and infusion-related events associated with the antifungal. Prospective clinical trial comparing lipid-complexed amphotericin B with liposomal and approved formulations of amphotericin B are essential to define potential differences in toxicity and efficacy.

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				P. Schöffski, M. Freund, R Wunder, D Petersen, C H Köhne, H Hecker, U Schubert, and A Ganser Safety and toxicity of amphotericin B in glucose 5% or intralipid 20% in neutropenic patients with pneumonia or fever of unknown origin: randomised study BMJ, August 8, 1998; 317(7155): 379 - 384. [Abstract] [Full Text]