AMPHOTERICIN-B TOXICITY REDUCED BY ADMINISTRATION IN FAT EMULSION

OBJECTIVE: To report a patient with intolerance to amphotericin B reve rsed 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 t herapy was initiated 2 days postchemotherapy; however, the patient con tinued to be febrile until day 7. At this time amphotericin B 35 mg/25 0 mL D5W over 4 hours was administered. Despite premedication, the pat ient experienced severe rigors, chills, and fever. As the result of co ntinuing infusion-related adverse events, the patient refused further therapy after the third daily dose. In an attempt to reduce the infusi on-related events, a trial of amphotericin B 35 mg/35 mL of fat emulsi on 20% was administered over 2 hours after patient consent was obtaine d. Premedication was administered and the patient tolerated therapy wi thout adverse events. Amphotericin B dosage escalations to 50 and 70 m g were tolerated similarly. During this treatment the patient became a febrile and the serum creatinine concentration decreased to normal. DI SCUSSION: Despite significant toxicities and the development of newer antifungal agents, amphotericin B remains the drug of choice for the e mpiric coverage of suspected fungal infection in neutropenic patients. Amphotericin B often exacerbates the nephrotoxicity of other agents c haracteristically prescribed in these patients. Furthermore, infusion- related events, if not intolerable, can dramatically reduce the patien t's quality of life. For these reasons, novel means of amphotericin B administration are being explored. CONCLUSIONS: The delivery of amphot ericin B in a lipid diluent may have substantial benefit in reducing t he nephrotoxicity and infusion-related events associated with the anti fungal. Prospective clinical trials comparing lipid-complexed amphoter icin B with liposomal and approved formulations of amphotericin B are essential to define potential differences in toxicity and efficacy.