title: High-dose weekly liposomal amphotericin b antifungal prophylaxis in patients undergoing liver transplantation: a prospective phase II trial.
abstract: BACKGROUND
  To assess the safety and tolerability of high-dose weekly (10 mg/kg) liposomal amphotericin B (LamB) for antifungal prophylaxis in liver transplantation (LT) recipients with predefined risk factors for invasive fungal infection (IFI), a prospective phase II noncomparative trial was performed at our center over a 4-year period.
  
  
  METHODS
  In the selected LT recipients, LamB was administered weekly until hospital discharge after LT for minimum 2 weeks. Criteria for early discontinuing prophylaxis were: (i) any adverse event (AE); (ii) suspicion of IFI. Safety and tolerability were assessed according to the incidence of grades 3 to 4 AEs based on Common Toxicity Criteria (CTC) classification. Post-LT follow-up was of 180 days.
  
  
  RESULTS
  Overall, 76 patients were included. Liposomal amphotericin B was started within a median of 1 (interquartile range, 1-4) day after LT. Overall, 66 of 76 (86.8%) patients completed the prophylaxis, 10 discontinued the study protocol: 6 for infusion-related AE, 4 for suspected IFI. Adverse events consisted of five cases of lumbar pain and one case of thoracic pain which occurred after a median of 1.5 (interquartile range, 1-2) LamB infusions. None of the patients reported CTC grades 3 to 4 hypokalemia, three reported CTC grade 3 acute renal injury, none of which were deemed directly attributable to LamB. No drug-drug interactions with immunosuppressive drugs were reported, and no episode of rejection occurred during the prophylaxis. In only two of the four patients with suspected IFI was the diagnosis of invasive candidiasis confirmed.
  
  
  CONCLUSIONS
  Our results suggest high-dose weekly LamB may be a safe prophylactic strategy for high-risk LT recipients.
authors.affiliation: 1 Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Italy. 2 Liver and Multi-Organ Transplant Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Italy. 3 Anesthesiology Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Italy. 4 Department of Pharmacy, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Giannella
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ercolani
authors.forename: Francesco
authors.initials: F
authors.lastname: Cristini
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Morelli
authors.forename: Michele
authors.initials: M
authors.lastname: Bartoletti
authors.forename: Valentina
authors.initials: V
authors.lastname: Bertuzzo
authors.forename: Sara
authors.initials: S
authors.lastname: Tedeschi
authors.forename: Stefano
authors.initials: S
authors.lastname: Faenza
authors.forename: Cristina
authors.initials: C
authors.lastname: Puggioli
authors.forename: Russell E
authors.initials: RE
authors.lastname: Lewis
authors.forename: Antonio Daniele
authors.initials: AD
authors.lastname: Pinna
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Viale
mesh_terms: D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007558:Italy; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000175:diagnosis / Q000382:microbiology / Q000517:prevention & control*; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B