Beschreibung:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p><jats:italic>Staphylococcus aureus</jats:italic> is a pathogen of major concern in both acute infections and chronic conditions such as chronic rhinosinusitis (CRS). Bacteriophage (phage) therapy has recently regained interest for its potential to treat infections caused by antibiotic resistant strains including Methicillin Resistant <jats:italic>Staphylococcus aureus</jats:italic> (MRSA). However, bacteria can adapt and become resistant to phages. The aim of this study is to determine the potential for antibiotics to overcome phage resistance.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The susceptibility of <jats:italic>S. aureus</jats:italic> clinical isolates (CIs) to phages J‐Sa36, Sa83 and Sa87 alone or in combination with protein synthesis inhibitor (PSI) antibiotics clindamycin, azithromycin and erythromycin was assessed using plaque spot assays, minimum inhibitory concentration (MIC) assays, double layer spot assays and resazurin assays. The safety and efficacy of subinhibitory PSI antibiotics in combination with phage was tested in a Sprague Dawley rat model of sinusitis infected with a phage resistant <jats:italic>S. aureus</jats:italic> CI.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>All three antibiotics at subinhibitory concentrations showed synergy when combined with all 3 phages against <jats:italic>S. aureus</jats:italic> CIs in planktonic and biofilm form and could sensitize phage‐resistant <jats:italic>S. aureus</jats:italic> to promote phage infection. The combination of topical subinhibitory clindamycin or azithromycin and phage was safe and could eradicate <jats:italic>S</jats:italic>. <jats:italic>aureus</jats:italic> sinonasal biofilms <jats:italic>in vivo</jats:italic>.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Subinhibitory concentrations of PSI antibiotics could sensitize phage‐resistant <jats:italic>S</jats:italic>. <jats:italic>aureus</jats:italic> and MRSA strains to phages <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic>. This data supports the potential use of phage‐PSI antibiotic combination therapies, in particular for difficult‐to‐treat infections with phage‐resistant <jats:italic>S</jats:italic>. <jats:italic>aureus</jats:italic> and MRSA strains.</jats:p></jats:sec>