Amphotericin B revisited: reassessment of toxicity

Although amphotericin B remains the mainstay of therapy for serious fungal infections, numerous acute and chronic toxicities make clinical usage difficult. Nevertheless, utilization of amphotericin B has increased dramatically in recent years. Accordingly, a study to reassess toxicity associated with the use of amphotericin in the modern era and to determine the aggregate impact toxicities have on the overall therapeutic course of patients was undertaken.

The charts of 50 patients at our institution who had received amphotericin B were retrospectively reviewed for the occurrence of drug-related acute and chronic toxicities and their impact on therapy. Patients evaluated were at least 21 years of age, had received at least 100 mg of amphotericin B, and were treated for at least 3 days. An analysis to investigate associations between drug administration variables and toxicities was also undertaken.

The mean age of study subjects were 54 years, the average duration of therapy was 19 days, and the mean cumulative dose of amphotericin B was 582 mg. Acute toxicities accompanying infusion occurred in 66% of all patients. Fever was experienced by 34% of study subjects and chills by 56%, with rates of 2.6 and 3.5 mean episodes per patient per treatment course, respectively. Other acute toxicities including hypotension were rare, and no patients exhibited bronchospasm or anaphylaxis. Nephrotoxicity occurred in 30 patients (60%). Baseline creatinine values in these patients rose by a mean of 1.55 mg/dL (137 mumol/L), with increases in creatinine ranging from 0.2 to 5.2 mg/dL (18 to 460 mumol/L). Analysis of six drug administration parameters by stepwise multiple linear regression failed to reveal any significant associations with nephrotoxicity. The mean nadir potassium value was 3.1 mEq/L (3.1 mmol/L) (range: 2.3 to 4.8 mEq/L [2.3 mmol/L]), with 45 of 50 patients (90%) receiving potassium supplementation (average daily supplement = 69 mEq). Only increasing amphotericin B concentration was correlated with an increased requirement for potassium supplementation (p less than 0.01, stepwise multiple linear regression).

Although clinically important toxicities continue to occur with usage of amphotericin B despite current methods of infusion and premedication, these are usually manageable and rarely limit the course of therapy.