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Searching for synergy: combining systemic daptomycin treatment with localised phage therapy for the treatment of experimental pneumonia due to MRSA

Luca G. Valente, Lea Federer, Manuela Iten, Denis Grandgirard, Stephen L. Leib, Stephan M. Jakob, Matthias Haenggi, David R. Cameron, Yok-Ai Que, Josef Prazak
Published: 27 September 2021

Abstract: Objective Bacteriophages (or phages) are viruses which infect and lyse bacteria. The therapeutic use of phages (phage therapy) has regained attention in the last decades as an alternative strategy to treat infections caused by antimicrobial-resistant bacteria. In clinical settings it is most likely that phages are administered adjunct to antibiotics. For successful phage therapy it is therefore crucial to investigate different phage-antibiotic combinations in vivo. This study aimed to elucidate the combinatorial effects of systemic daptomycin and nebulised bacteriophages for the treatment of experimental pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). Results Using a rat model of ventilator-associated pneumonia caused by MRSA, the simultaneous application of intravenous daptomycin and nebulised phages was not superior to aerophage therapy alone at improving animal survival (55% vs. 50%), or reducing bacterial burdens in the lungs, or spleen. Thus, this combination does not seem to be of benefit for use in patients with MRSA pneumonia.
Keywords: Ventilator-associated pneumonia / Nebulized bacteriophages / Methicillin-resistant Staphylococcus aureus / Phage-antibiotic interactions

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