title: Impact of targeted antifungal prophylaxis in heart transplant recipients at high risk for early invasive fungal infection.
abstract: BACKGROUND
  Invasive fungal infection (IFI) is associated with high mortality after heart transplantation (HTx). After two undiagnosed fatal cases of early disseminated fungal infections in our heart transplant program, a retrospective analysis was conducted to identify risk factors for the development of IFI and implement a new antifungal prophylaxis policy.
  
  
  METHODS
  Clinical characteristics of HTx recipients hospitalized in our center (2004-2010) were recorded (Period 1), and risk factors associated with IFI were investigated using Cox regression analysis. From October 2010 to October 2012 (Period 2), targeted caspofungin prophylaxis was administered to all recipients at high risk for IFI, based on the results of the Period 1 analysis.
  
  
  RESULTS
  During Period 1, 10% (6/59) of the patients developed IFI at a median onset of 9 days after transplantation. By multivariate analysis, the use of posttransplant extracorporeal membrane oxygenation (ECMO) was the strongest predictor for fungal infection (OR, 29.93; 95% CI, 1.51-592.57, P=0.03), whereas renal replacement therapy (RRT) and Aspergillus colonization were significant predictors only by univariate analysis. During Period 2, only 4% (1/26) of the patients developed IFI. In patients at high risk for IFI, antifungal prophylaxis was administered to 17% (4/23) in Period 1 versus 100% (13/13) in Period 2 (P<0.01). By survival analysis, antifungal prophylaxis was associated with a reduction in 90-day IFI incidence (HR, 0.14; 95% CI, 0.03-0.84, P=0.03) and 30-day mortality (HR, 0.25; 95% CI, 0.09-0.8, P=0.02).
  
  
  CONCLUSIONS
  Extracorporeal membrane oxygenation was identified an important risk factor for IFI after HTx, and its use may require targeted administration of antifungal prophylaxis in the immediate posttransplant period.
authors: 1 Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. 2 Transplantation Center, Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. 3 Service of Cardiology, Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. 4 Service of Cardiovascular Surgery, Department of Surgery, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. 5 Institute of Microbiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland. 6 Address correspondence to: Frederic Tissot, M.D., Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland.
authors: Frederic
authors: F
authors: Tissot
authors: Manuel
authors: M
authors: Pascual
authors: Roger
authors: R
authors: Hullin
authors: Patrick
authors: P
authors: Yerly
authors: Piergiorgio
authors: P
authors: Tozzi
authors: Pascal
authors: P
authors: Meylan
authors: Oriol
authors: O
authors: Manuel
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use*; D001230:Aspergillus / Q000187:drug effects; D000077336:Caspofungin; D054714:Echinocandins / Q000008:administration & dosage; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000628:therapy*; D016027:Heart Transplantation / Q000379:methods*; D006760:Hospitalization; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D055666:Lipopeptides; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control*; D011184:Postoperative Period; D016016:Proportional Hazards Models; D017582:Renal Replacement Therapy; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D007166:Immunosuppressive Agents; D055666:Lipopeptides; D000077336:Caspofungin