Bacteriophages Combined With Subtherapeutic Doses of Flucloxacillin Act Synergistically Against Staphylococcus aureus Experimental Infective Endocarditis.

Details

Serval ID
serval:BIB_28CEC1719C12
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Bacteriophages Combined With Subtherapeutic Doses of Flucloxacillin Act Synergistically Against Staphylococcus aureus Experimental Infective Endocarditis.
Journal
Journal of the American Heart Association
Author(s)
Save J., Que Y.A., Entenza J.M., Kolenda C., Laurent F., Resch G.
ISSN
2047-9980 (Electronic)
ISSN-L
2047-9980
Publication state
Published
Issued date
02/2022
Peer-reviewed
Oui
Volume
11
Number
3
Pages
e023080
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Background The potential of phage therapy for the treatment of endovascular Staphylococcus aureus infections remains to be evaluated. Methods and Results The efficacy of a phage cocktail combining Herelleviridae phage vB_SauH_2002 and Podoviriae phage 66 was evaluated against a methicillin-sensitive S. aureus strain in vitro and in vivo in a rodent model of experimental endocarditis. Six hours after bacterial challenge, animals were treated with (1) the phage cocktail. (2) subtherapeutic flucloxacillin dosage, (3) combination of the phage cocktail and flucloxacillin, or (4) saline. Bacterial loads in cardiac vegetations at 30 hours were the primary outcome. Secondary outcomes were phage loads at 30 hours in cardiac vegetations, blood, spleen, liver, and kidneys. We evaluated phage resistance 30 hours post infection in vegetations of rats under combination treatment. In vitro, phages synergized against S. aureus planktonic cells and the cocktail synergized with flucloxacillin to eradicated biofilms. In infected animals, the phage cocktail achieved bacteriostatic effect. The addition of low-dose flucloxacillin elevated bacterial suppression (∆ of -5.25 log <sub>10</sub> colony forming unit/g [CFU/g] versus treatment onset, P<0.0001) and synergism was confirmed (∆ of -2.15 log <sub>10</sub> CFU/g versus low-dose flucloxacillin alone, P<0.01). Importantly, 9/12 rats given the combination treatment had sterile vegetations at 30 hours. In vivo phage replication was partially suppressed by the antibiotic and selection of resistance to the Podoviridae component of the phage cocktail occurred. Plasma-mediated inhibition of phage killing activity was observed in vitro. Conclusions Combining phages with a low-dose standard of care antibiotic represents a promising strategy for the treatment of S. aureus infective endocarditis.
Keywords
Staphylococcus aureus, endocarditis, phage antibiotic synergism, phage therapy
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2022 20:27
Last modification date
19/03/2022 7:32
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