title: Antifungal prophylaxis in liver transplant recipients: one size does not fit all.
abstract: BACKGROUND
  Targeted antifungal prophylaxis against Candida species or against Candida species and Aspergillus species, according to individual patient risk factors (RFs), is recommended by experts. However, recent studies have reported fluconazole is as effective as broader spectrum antifungals for preventing invasive fungal infection (IFI) after liver transplantation (LT).
  
  
  METHODS
  We performed a retrospective cohort study of all adult patients who underwent LT at our 1420-bed tertiary teaching hospital, from June 2010 to December 2014, to assess the rate and etiology of IFI within 100 days after LT, to investigate the compliance with targeted prophylaxis, and to analyze risk factors for developing IFI.
  
  
  RESULTS
  In total, 303 patients underwent LT. Patients were classified as having low (no RFs), intermediate (1 RF for invasive candidiasis [IC]), and high risk (1 RF for invasive aspergillosis [IA] or ≥2 RFs for IC) for IFI in 20%, 30%, and 50% of cases, respectively. A total of 139 patients received antifungal prophylaxis: 98 with a mold-active drug and 41 with fluconazole. Overall adherence to targeted prophylaxis was 53%. Nineteen patients (6.3%) developed IFI: 7 IC and 12 IA. Multivariate Cox regression analysis, adjusted for median model for end-stage liver disease score at LT, stratification risk group, and adherence to targeted prophylaxis, showed that graft dysfunction, renal replacement therapy, and prophylaxis with fluconazole were independent risk factors for IFI. Seven of the 9 patients who received fluconazole prophylaxis and developed IFI were classified as having high risk for IFI, and 6 developed IA.
  
  
  CONCLUSIONS
  Recommended stratification is accurate for predicting patients at very high risk for IFI, who should receive prophylaxis with a mold-active drug.
authors.affiliation: Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Giannella
authors.affiliation: Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bartoletti
authors.affiliation: Liver and Multi-Organ Transplant Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Morelli
authors.affiliation: Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cristini
authors.affiliation: Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Tedeschi
authors.affiliation: Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Campoli
authors.affiliation: Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Tumietto
authors.affiliation: Liver and Multi-Organ Transplant Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Bertuzzo
authors.affiliation: Liver and Multi-Organ Transplant Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Ercolani
authors.affiliation: Anesthesiology Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Faenza
authors.affiliation: Liver and Multi-Organ Transplant Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: A D
authors.initials: AD
authors.lastname: Pinna
authors.affiliation: Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: R E
authors.initials: RE
authors.lastname: Lewis
authors.affiliation: Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Viale
mesh_terms: D019072:Antibiotic Prophylaxis / Q000379:methods*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001230:Aspergillus / Q000302:isolation & purification; D002175:Candida / Q000302:isolation & purification; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D000072742:Invasive Fungal Infections / Q000453:epidemiology / Q000382:microbiology / Q000517:prevention & control*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D066027:Transplant Recipients; D016903:Drug Monitoring
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole
keywords: antifungal prophylaxis; invasive fungal infection; liver transplantation