Bacteriophages Combined With Subtherapeutic Doses of Flucloxacillin Act Synergistically Against Staphylococcus aureus Experimental Infective Endocarditis.
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- doi: 10.1161/JAHA.121.023080
- issn: 2047-9980
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J. Save et al., « Bacteriophages Combined With Subtherapeutic Doses of Flucloxacillin Act Synergistically Against Staphylococcus aureus Experimental Infective Endocarditis. », Serveur académique Lausannois, ID : 10.1161/JAHA.121.023080
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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 10 colony forming unit/g [CFU/g] versus treatment onset, P