Bacteriophages Improve Outcomes in Experimental Staphylococcus aureus Ventilator-associated Pneumonia.
Details
Serval ID
serval:BIB_2CF5B9B31B06
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Bacteriophages Improve Outcomes in Experimental Staphylococcus aureus Ventilator-associated Pneumonia.
Journal
American journal of respiratory and critical care medicine
ISSN
1535-4970 (Electronic)
ISSN-L
1073-449X
Publication state
Published
Issued date
01/11/2019
Peer-reviewed
Oui
Volume
200
Number
9
Pages
1126-1133
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Rationale: Infections caused by multidrug-resistant bacteria are a major clinical challenge. Phage therapy is a promising alternative antibacterial strategy.Objectives: To evaluate the efficacy of intravenous phage therapy for the treatment of ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus in rats.Methods: In a randomized, blinded, controlled experimental study, we compared intravenous teicoplanin (3 mg/kg, n = 12), a cocktail of four phages (2-3 × 10 <sup>9</sup> plaque-forming units/ml of 2003, 2002, 3A, and K; n = 12), and a combination of both (n = 11) given 2, 12, and 24 hours after induction of pneumonia, and then once daily for 4 days. The primary outcome was survival at Day 4. Secondary outcomes were bacterial and phage densities in lungs and spleen, histopathological scoring of infection within the lungs, and inflammatory biomarkers in blood.Measurements and Main Results: Treatment with either phages or teicoplanin increased survival from 0% to 58% and 50%, respectively (P < 0.005). The combination of phages and antibiotics did not further improve outcomes (45% survival). Animal survival correlated with reduced bacterial burdens in the lung (1.2 × 10 <sup>6</sup> cfu/g of tissue for survivors vs. 1.2 × 10 <sup>9</sup> cfu/g for nonsurviving animals; P < 0.0001), as well as improved histopathological outcomes. Phage multiplication within the lung occurred during treatment. IL-1β increased in all treatment groups over the course of therapy.Conclusions: Phage therapy was as effective as teicoplanin in improving survival and decreasing bacterial load within the lungs of rats infected with methicillin-resistant S. aureus. Combining antibiotics with phage therapy did not further improve outcomes.
Keywords
Animals, Anti-Bacterial Agents/therapeutic use, Bacteriophages, Disease Models, Animal, Male, Methicillin-Resistant Staphylococcus aureus, Phage Therapy, Pneumonia, Ventilator-Associated/microbiology, Pneumonia, Ventilator-Associated/therapy, Rats, Rats, Wistar, Staphylococcal Infections/microbiology, Staphylococcal Infections/therapy, Teicoplanin/therapeutic use, antibiotic resistance, bacteriophage, microbial, pneumonia, ventilator associated
Pubmed
Web of science
Create date
18/07/2019 16:22
Last modification date
05/04/2020 5:20