Prospective study of amphotericin B formulations in immunocompromised patients in 4 European countries.

BACKGROUND: Amphotericin B is a widely used broad-spectrum antifungal agent, despite being associated with significant adverse events, including nephrotoxicity.
METHODS: The present prospective study collected data on outcomes for 418 adult patients treated consecutively with polyenes in hematology and oncology wards in 20 hospitals in Europe.
RESULTS: Patients initially received amphotericin B deoxycholate (62% of patients), liposomal amphotericin B (27%), or other lipid formulations of amphotericin B (11%). Of the patients initially treated with amphotericin B deoxycholate, 36% had therapy switched to lipid formulations of amphotericin B, primarily because of increased serum creatinine levels (in 45.7% of patients) or other amphotericin B-attributable adverse events (in 41.3% of patients). Nephrotoxicity, which was defined as a > or = 50% increase in the serum creatinine level, developed in 57% of patients with normal kidney function at baseline. Predictors of nephrotoxicity included formulation type and duration of treatment. Compared with patients without nephrotoxicity, patients with nephrotoxicity had a higher mortality rate (24%), and their mean length of stay in the hospital was prolonged by 8.6 days. Slight increases in the serum creatinine level (i.e., > or = 50%) were associated with a significantly longer stay in the hospital. Severe nephrotoxicity (i.e., a > or = 200% increase in the serum creatinine level) was a significant predictor of death, as were severe underlying medical conditions and documented fungal infection.
CONCLUSION: This prospective study confirmed that, in European hospitals, amphotericin B formulations have a major influence on the length of stay in the hospital and nephrotoxicity-associated mortality.