title: Comparative safety of amphotericin B lipid complex and amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients.
abstract: BACKGROUND
  Aerosolized administrations of amphotericin B deoxycholate (AmBd) and amphotericin B lipid complex (ABLC) in lung transplant recipients were compared for safety and tolerability. The incidence of invasive fungal infections in patients receiving aerosolized amphotericin B formulations as sole prophylaxis was determined.
  
  
  METHODS
  A prospective, randomized (1:1), double-blinded trial was conducted with 100 subjects. AmBd and ABLC were administered postoperatively by nebulizer at doses of 25 mg and 50 mg, respectively, which were doubled in mechanically ventilated patients. The planned treatment was once every day for 4 days, then once per week for 7 weeks. Treatment-related adverse events and invasive fungal infections were quantitated for 2 months after study drug initiation.
  
  
  RESULTS
  Intent-to-treat analysis revealed study drug was discontinued for intolerance in 6 of 49 (12.2%) and 3 of 51 (5.9%) patients in the AmBd- and ABLC-treated groups, respectively (p=0.313). Subjects receiving AmBd were more likely to have experienced an adverse event (odds ratio 2.16, 95% confidence interval 1.10, 4.24, p=0.02). Primary prophylaxis failure within 2 months of study drug initiation was observed in 7 of 49 (14.3%) AmBd-treated patients and 6 of 51 (11.8%) ABLC-treated patients. No fungal pneumonias were observed. Only two (2%) patients experienced documented primary prophylaxis failure with Aspergillus infections within the follow-up period.
  
  
  CONCLUSIONS
  Both aerosol AmBd and ABLC appear to be associated with a low rate of invasive pulmonary fungal infection in the early posttransplant period. Patients receiving ABLC were less likely to experience a treatment-related adverse event.
authors.affiliation: Division of Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA. richard.drew@duke.edu
authors.forename: Richard H
authors.initials: RH
authors.lastname: Drew
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dodds Ashley
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Benjamin
authors.forename: R
authors.initials: R
authors.lastname: Duane Davis
authors.forename: Scott M
authors.initials: SM
authors.lastname: Palmer
authors.forename: John R
authors.initials: JR
authors.lastname: Perfect
mesh_terms: D000293:Adolescent; D000328:Adult; D000336:Aerosols; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D016041:Heart-Lung Transplantation / Q000502:physiology; D006801:Humans; D008171:Lung Diseases / Q000145:classification / Q000601:surgery; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control*; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010715:Phosphatidylglycerols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000517:prevention & control*; D044469:Racial Groups; D012189:Retrospective Studies
chemical_list: D000336:Aerosols; D004338:Drug Combinations; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination