title: Effectiveness of bacteriophages in the sputum of cystic fibrosis patients.
abstract: Bacteriophages have been shown to be effective for treating acute infections of the respiratory tract caused by antibiotic-resistant bacteria in animal models, but no evidence has yet been presented of their activity against pathogens in complex biological samples from chronically infected patients. We assessed the efficacy of a cocktail of ten bacteriophages infecting Pseudomonas aeruginosa following its addition to 58 sputum samples from cystic fibrosis (CF) patients collected at three different hospitals. Ten samples that did not contain P. aeruginosa were not analysed further. In the remaining 48 samples, the addition of bacteriophages led to a significant decrease in the levels of P. aeruginosa strains, as shown by comparison with controls, taking two variables (time and bacteriophages) into account (p = 0.024). In 45.8% of these samples, this decrease was accompanied by an increase in the number of bacteriophages. We also tested each of the ten bacteriophages individually against 20 colonies from each of these 48 samples and detected bacteriophage-susceptible bacteria in 64.6% of the samples. An analysis of the clinical data revealed no correlation between patient age, sex, duration of P. aeruginosa colonization, antibiotic treatment, FEV1 (forced expiratory volume in the first second) and the efficacy of bacteriophages. The demonstration that bacteriophages infect their bacterial hosts in the sputum environment, regardless of the clinical characteristics of the patients, represents a major step towards the development of bacteriophage therapy to treat chronic lung infections.
authors.affiliation: Department of Microbiology, Institut Pasteur, Molecular Biology of the Gene in Extremophiles Unit, Paris, France; Cellule Pasteur UPMC, Université Pierre et Marie Curie, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Saussereau
authors.forename: I
authors.initials: I
authors.lastname: Vachier
authors.forename: R
authors.initials: R
authors.lastname: Chiron
authors.forename: B
authors.initials: B
authors.lastname: Godbert
authors.forename: I
authors.initials: I
authors.lastname: Sermet
authors.forename: N
authors.initials: N
authors.lastname: Dufour
authors.forename: J-P
authors.initials: JP
authors.lastname: Pirnay
authors.forename: D
authors.initials: D
authors.lastname: De Vos
authors.forename: F
authors.initials: F
authors.lastname: Carrié
authors.forename: N
authors.initials: N
authors.lastname: Molinari
authors.forename: L
authors.initials: L
authors.lastname: Debarbieux
mesh_terms: D000293:Adolescent; D000328:Adult; D058491:Bacterial Load; D001691:Biological Therapy / Q000379:methods; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D050296:Microbial Viability; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000382:microbiology*; D017105:Pseudomonas Phages / Q000254:growth & development*; D011550:Pseudomonas aeruginosa / Q000821:virology*; D013183:Sputum / Q000382:microbiology* / Q000821:virology*; D013997:Time Factors; D055815:Young Adult
keywords: Chronic infection; Pseudomonas aeruginosa; phage therapy; pulmonary infection