Synergistic Interaction Between Phage Therapy and Antibiotics Clears Pseudomonas Aeruginosa Infection in Endocarditis and Reduces Virulence.

Détails

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_D5FC8128CA16
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Synergistic Interaction Between Phage Therapy and Antibiotics Clears Pseudomonas Aeruginosa Infection in Endocarditis and Reduces Virulence.
Périodique
The Journal of infectious diseases
Auteur(s)
Oechslin F., Piccardi P., Mancini S., Gabard J., Moreillon P., Entenza J.M., Resch G., Que Y.A.
ISSN
1537-6613 (Electronic)
ISSN-L
0022-1899
Statut éditorial
Publié
Date de publication
01/03/2017
Peer-reviewed
Oui
Volume
215
Numéro
5
Pages
703-712
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Increasing antibiotic resistance warrants therapeutic alternatives. Here we investigated the efficacy of bacteriophage-therapy (phage) alone or combined with antibiotics against experimental endocarditis (EE) due to Pseudomonas aeruginosa, an archetype of difficult-to-treat infection.
In vitro fibrin clots and rats with aortic EE were treated with an antipseudomonas phage cocktail alone or combined with ciprofloxacin. Phage pharmacology, therapeutic efficacy, and resistance were determined.
In vitro, single-dose phage therapy killed 7 log colony-forming units (CFUs)/g of fibrin clots in 6 hours. Phage-resistant mutants regrew after 24 hours but were prevented by combination with ciprofloxacin (2.5 × minimum inhibitory concentration). In vivo, single-dose phage therapy killed 2.5 log CFUs/g of vegetations in 6 hours (P < .001 vs untreated controls) and was comparable with ciprofloxacin monotherapy. Moreover, phage/ciprofloxacin combinations were highly synergistic, killing >6 log CFUs/g of vegetations in 6 hours and successfully treating 64% (n = 7/11) of rats. Phage-resistant mutants emerged in vitro but not in vivo, most likely because resistant mutations affected bacterial surface determinants important for infectivity (eg, the pilT and galU genes involved in pilus motility and LPS formation).
Single-dose phage therapy was active against P. aeruginosa EE and highly synergistic with ciprofloxacin. Phage-resistant mutants had impaired infectivity. Phage-therapy alone or combined with antibiotics merits further clinical consideration.

Mots-clé
Animals, Anti-Bacterial Agents/pharmacology, Ciprofloxacin/pharmacology, Drug Resistance, Multiple, Bacterial, Endocarditis/microbiology, Endocarditis/therapy, Female, Microbial Sensitivity Tests, Phage Therapy/methods, Pseudomonas Infections/therapy, Pseudomonas aeruginosa/drug effects, Pseudomonas aeruginosa/pathogenicity, Rats, Rats, Wistar, Virulence
Pubmed
Open Access
Oui
Création de la notice
08/01/2017 16:07
Dernière modification de la notice
09/05/2019 1:51
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