title: Short term Candida albicans colonization reduces Pseudomonas aeruginosa-related lung injury and bacterial burden in a murine model.
abstract: BACKGROUND
  Pseudomonas aeruginosa is a frequent cause of ventilator-acquired pneumonia (VAP). Candida tracheobronchial colonization is associated with higher rates of VAP related to P. aeruginosa. This study was designed to investigate whether prior short term Candida albicans airway colonization modulates the pathogenicity of P. aeruginosa in a murine model of pneumonia and to evaluate the effect of fungicidal drug caspofungin.
  
  
  METHODS
  BALB/c mice received a single or a combined intratracheal administration of C. albicans (1 × 10(5) CFU/mouse) and P. aeruginosa (1 × 10(7) CFU/mouse) at time 0 (T0) upon C. albicans colonization, and Day 2. To evaluate the effect of antifungal therapy, mice received caspofungin intraperitoneally daily, either from T0 or from Day 1 post-colonization. After sacrifice at Day 4, lungs were analyzed for histological scoring, measurement of endothelial injury, and quantification of live P. aeruginosa and C. albicans. Blood samples were cultured for dissemination.
  
  
  RESULTS
  A significant decrease in lung endothelial permeability, the amount of P. aeruginosa, and bronchiole inflammation was observed in case of prior C. albicans colonization. Mortality rate and bacterial dissemination were unchanged by prior C. albicans colonization. Caspofungin treatment from T0 (not from Day 1) increased their levels of endothelial permeability and lung P. aeruginosa load similarly to mice receiving P. aeruginosa alone.
  
  
  CONCLUSIONS
  P. aeruginosa-induced lung injury is reduced when preceded by short term C. albicans airway colonization. Antifungal drug caspofungin reverses that effect when used from T0 and not from Day 1.
authors.affiliation: Department of Infectious Diseases, Croix-Rousse Hospital, 104 Grande-Rue de la Croix-Rousse, Lyon, F-69004, France. florence.ader@chu-lyon.fr
authors.forename: Florence
authors.initials: F
authors.lastname: Ader
authors.forename: Samir
authors.initials: S
authors.lastname: Jawhara
authors.forename: Saad
authors.initials: S
authors.lastname: Nseir
authors.forename: Eric
authors.initials: E
authors.lastname: Kipnis
authors.forename: Karine
authors.initials: K
authors.lastname: Faure
authors.forename: Fanny
authors.initials: F
authors.lastname: Vuotto
authors.forename: Chanez
authors.initials: C
authors.lastname: Chemani
authors.forename: Boualem
authors.initials: B
authors.lastname: Sendid
authors.forename: Daniel
authors.initials: D
authors.lastname: Poulain
authors.forename: Benoit
authors.initials: B
authors.lastname: Guery
mesh_terms: D000818:Animals; D058491:Bacterial Load / Q000379:methods / Q000502:physiology*; D002176:Candida albicans / Q000254:growth & development*; D015169:Colony Count, Microbial / Q000379:methods; D004195:Disease Models, Animal; D055370:Lung Injury / Q000382:microbiology* / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D011552:Pseudomonas Infections / Q000503:physiopathology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000254:growth & development* / Q000302:isolation & purification; D011897:Random Allocation; D013997:Time Factors