title: Prevention and diagnosis of invasive fungal disease in high-risk patients within an integrative care pathway.
abstract: OBJECTIVE
  The aim of this study was to assess the clinical utility of enhanced diagnostics on the management of invasive fungal disease in high risk patients within an integrated care pathway and to audit compliance and efficacy of antifungal prophylaxis.
  
  
  METHODS
  A cohort of 549 high risk haematology and stem-cell transplant recipients was followed over a 5 year period. The routine standard of care involved the use of antimould prophylaxis and a neutropenic care pathway utilizing twice weekly antigen and PCR testing.
  
  
  RESULTS
  Prophylaxis with itraconazole was poorly tolerated and therapeutic levels could not be maintained. Antigen testing and PCR showed good clinical utility in the management of invasive aspergilosis with high sensitivity (98%) and negative predictive value (99.6%) when both tests were used together, allowing a diagnosis IA to be excluded and obviating the need for empirical antifungal agents. When used serially, multiple positive PCR and antigen test results enabled accurate diagnosis of IA with a specificity of 95% and a positive likelihood ratio of 11. Biomarkers preceded clinical signs in 85% of proven and probable invasive disease.
  
  
  CONCLUSIONS
  The combination of both tests showed optimum clinical utility for the diagnosis and management of IA in this high risk group.
authors: Department of Medical Microbiology and Infectious Diseases, Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. Barnesra@cf.ac.uk
authors: Rosemary A
authors: RA
authors: Barnes
authors: Kate
authors: K
authors: Stocking
authors: Sarah
authors: S
authors: Bowden
authors: Matthew H
authors: MH
authors: Poynton
authors: P Lewis
authors: PL
authors: White
mesh_terms: D000328:Adult; D019072:Antibiotic Prophylaxis; D000935:Antifungal Agents / Q000627:therapeutic use; D000946:Antigens, Fungal / Q000097:blood; D001228:Aspergillosis / Q000175:diagnosis* / Q000188:drug therapy / Q000517:prevention & control*; D058365:Candidiasis, Invasive / Q000175:diagnosis* / Q000188:drug therapy / Q000517:prevention & control*; D015331:Cohort Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D016133:Polymerase Chain Reaction; D011183:Postoperative Complications / Q000175:diagnosis / Q000188:drug therapy / Q000517:prevention & control; D012372:ROC Curve; D033581:Stem Cell Transplantation
chemical_list: D000935:Antifungal Agents; D000946:Antigens, Fungal
keywords: Antigen detection; Diagnosis; Invasive fungal disease; PCR