title: Prospective study of amphotericin B formulations in immunocompromised patients in 4 European countries.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Klinikum Johannes Gutenberg Universität, III. Medizinische Klinik und Poliklinik, Langenbeckstr. 1, 55101 Mainz, Germany. ullmann@uni-mainz.de
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ullmann
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
authors.forename: Andrea
authors.initials: A
authors.lastname: Tramarin
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Barnes
authors.forename: Wenchen
authors.initials: W
authors.lastname: Wu
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Gerlach
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Krobot
authors.forename: William C
authors.initials: WC
authors.lastname: Gerth
mesh_terms: D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000009:adverse effects* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005060:Europe; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007674:Kidney Diseases / Q000139:chemically induced* / Q000401:mortality; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000401:mortality; D011090:Polyenes; D011446:Prospective Studies
chemical_list: D000935:Antifungal Agents; D011090:Polyenes; D000666:Amphotericin B