title: Universal antifungal therapy is not needed in persistent febrile neutropenia: a tailored diagnostic and therapeutic approach.
abstract: BACKGROUND
  Giving antifungal therapy exclusively to selected patients with persistent febrile neutropenia may avoid over-treatment without increasing mortality. The aim of this study was to validate an innovative diagnostic and therapeutic approach based on assessing patients' risk profile and clinical criteria in order to select those patients requiring antifungal therapy. The efficacy of this approach was compared to that of universal empirical antifungal therapy.
  
  
  METHODS
  This was a prospective study which included all consecutive adult hematology patients with neutropenia and fever refractory to 5 days of empirical antibacterial therapy admitted to a teaching hospital in Spain over a 2-year period. A diagnostic and therapeutic approach based on clinical criteria and risk profile was applied in order to select patients for antifungal therapy. The sensitivity, specificity and negative predictive value of this approach and also the overall success rate, according to the same criteria of efficacy described in classical clinical trials, were analyzed.
  
  
  RESULTS
  Eighty-five episodes were included, 35 of them (41.2%) in patients at high risk of invasive fungal infections. Antifungal therapy was not indicated in 33 episodes (38.8%). The overall incidence of proven and probable invasive fungal infections was 14.1%, all of which occurred in patients who had received empirical antifungal therapy. The 30-day crude mortality rate was 15.3% and the invasive fungal infection-related mortality rate was 2.8% (2/72). The overall success rate following the diagnostic and therapeutic approach was 36.5% compared with 33.9% and 33.7% obtained in the trial by Walsh et al. The sensitivity, specificity and negative predictive value of the study approach were 100%, 52.4% and 100%, respectively.
  
  
  CONCLUSIONS
  Based on the high negative predictive value of this diagnostic and therapeutic approach in persistent febrile neutropenia patients with hematologic malignancies or patients who have received a hematopoietic stem cell transplant, the approach is useful for identifying patients who are not likely to develop invasive fungal infection and do not, therefore, require antifungal therapy. The effectiveness of the strategy is similar to that of universal empirical antifungal therapy reported in controlled trials.
authors: Spanish Network for Research in Infectious Diseases, Sevilla, Spain.
authors: Manuela
authors: M
authors: Aguilar-Guisado
authors: Almudena
authors: A
authors: Martín-Peña
authors: Ildefonso
authors: I
authors: Espigado
authors: Maite
authors: M
authors: Ruiz Pérez de Pipaon
authors: José
authors: J
authors: Falantes
authors: Fátima
authors: F
authors: de la Cruz
authors: José M
authors: JM
authors: Cisneros
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use*; D005334:Fever / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D008875:Middle Aged; D009181:Mycoses / Q000175:diagnosis* / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D009503:Neutropenia / Q000175:diagnosis* / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000935:Antifungal Agents