title: Candida in the respiratory tract secretions of critically ill patients and the impact of antifungal treatment: a randomized placebo controlled pilot trial (CANTREAT study).
abstract: OBJECTIVE
  Candida spp. are frequently recovered from endotracheal secretions in critically ill patients suspected of having ventilator-associated pneumonia. Observational studies reported an association with worse clinical outcomes but the effect of antifungal therapy in these patients remains unclear. We designed this pilot study to assess the feasibility of a larger trial and to evaluate inflammatory profiles and clinical outcomes in these patients.
  
  
  METHODS
  We conducted a double-blind, placebo-controlled, multicenter pilot randomized trial of antifungal therapy in critically ill patients with a clinical suspicion of ventilator-associated pneumonia with positive airway secretion specimens for Candida spp. We also included an observational group without Candida spp. in their airway secretions. We measured recruitment rate, inflammatory and innate immune function profiles over time, and clinical outcomes.
  
  
  RESULTS
  We recruited 60 patients into the randomized trial and 29 patients into the observational study. Markers of inflammation and all clinical outcomes were comparable between placebo and antifungal treatment group at baseline and over time. At baseline, plasma TNF-α levels were higher in patients with VAP and Candida compared to the observational group (mean ± SD) (21.8 ± 23.1 versus 12.4 ± 9.3 pg/ml, p = 0.02) and these patients had lower innate immune function as evidenced by reduced whole blood ex vivo LPS-induced TNF-α production capacity (854.8 ± 855.2 versus 1,559.4 ± 1,290.6 pg/ml, p = 0.01).
  
  
  CONCLUSIONS
  This study does not provide evidence to support a larger trial examining the efficacy of empiric antifungal treatment in patients with a clinical suspicion of ventilator-associated pneumonia and Candida in the endotracheal secretions. The presence of Candida in the lung may be associated with persistent inflammation and immunosuppression.
authors: Département de Médecine, Centre de recherche de l'Hôpital du Sacré-Coeur de Montréal, Université de Montréal, 5400 Gouin Ouest, Montreal, Canada, m.albert@umontreal.ca.
authors: Martin
authors: M
authors: Albert
authors: David
authors: D
authors: Williamson
authors: John
authors: J
authors: Muscedere
authors: Francois
authors: F
authors: Lauzier
authors: Coleman
authors: C
authors: Rotstein
authors: Salmaan
authors: S
authors: Kanji
authors: Xuran
authors: X
authors: Jiang
authors: Mark
authors: M
authors: Hall
authors: Daren
authors: D
authors: Heyland
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D002175:Candida / Q000302:isolation & purification*; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology*; D016638:Critical Illness; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000382:microbiology*; D011446:Prospective Studies; D012137:Respiratory System / Q000378:metabolism
chemical_list: D000935:Antifungal Agents