title: Nebulised amphotericin B to eradicate Candida colonisation from the respiratory tract in critically ill patients receiving selective digestive decontamination: a cohort study.
abstract: BACKGROUND
  Colonisation of the lower respiratory tract with Candida species occurs in 25% of mechanically ventilated critically ill patients, and is associated with increased morbidity. Nebulised amphotericin B has been used to eradicate Candida as part of selective decontamination of the digestive tract (SDD) protocols, but its effectiveness is unknown. We aimed to determine the effectiveness of nebulised amphotericin B in eradicating Candida respiratory tract colonisation in patients receiving SDD.
  
  
  METHODS
  We included consecutive mechanically ventilated patients during a four-year period. Microbiological screening was performed upon admission and twice weekly thereafter according to a standardised protocol. A colonisation episode was defined as the presence of Candida species in two consecutive sputum samples taken at least one day apart. To correct for time-varying bias and possible confounding, we used a multistate approach and performed time-varying Cox regression with adjustment for age, disease severity, Candida load at baseline and concurrent corticosteroid use.
  
  
  RESULTS
  Among 1,819 patients, colonisation with Candida occurred 401 times in 363 patients; 333 of these events were included for analysis. Decolonisation occurred in 51 of 59 episodes (86%) and in 170 of 274 episodes (62%) in patients receiving and not receiving nebulised amphotericin B, respectively. Nebulised amphotericin B was associated with an increased rate of Candida eradication (crude HR 2.0; 95% CI 1.4 to 2.7, adjusted HR 2.2; 95% CI 1.6 to 3.0). Median times to decolonisation were six and nine days, respectively. The incidence rate of ventilator-associated pneumonia, length of stay and mortality did not differ between both groups.
  
  
  CONCLUSIONS
  Nebulised amphotericin B reduces the duration of Candida colonisation in the lower respiratory tracts of mechanically ventilated critically ill patients receiving SDD, but data remain lacking that this is associated with a meaningful improvement in clinical outcomes. Until more evidence becomes available, nebulised amphotericin B should not be used routinely as part of the SDD protocol.
authors.forename: David S Y
authors.initials: DS
authors.lastname: Ong
authors.forename: Peter M C
authors.initials: PM
authors.lastname: Klein Klouwenberg
authors.forename: Cristian
authors.initials: C
authors.lastname: Spitoni
authors.forename: Marc J M
authors.initials: MJ
authors.lastname: Bonten
authors.forename: Olaf L
authors.initials: OL
authors.lastname: Cremer
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage*; D000935:Antifungal Agents / Q000008:administration & dosage*; D002175:Candida / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy*; D016638:Critical Illness; D003666:Decontamination / Q000379:methods; D004064:Digestive System / Q000382:microbiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D009426:Netherlands; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000382:microbiology*; D012137:Respiratory System / Q000382:microbiology*
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B