• Josef Prazak, Luca Valente, Manuela Iten, Denis Grandgirard, Stephen L Leib, Stephan M Jakob, Matthias Haenggi, Yok-Ai Que, and David R Cameron.
• Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
• Crit. Care Med. 2020 Jul 1; 48 (7): 1042-1046.

ObjectivesThere is a need for alternative strategies to combat and prevent antibiotic-resistant bacterial infections. Here, we assessed the potential for bacteriophage prophylaxis in the context of experimental ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus in rats.DesignNebulized phages (aerophages) were delivered to the lungs of rats using a modified vibrating mesh aerosol drug delivery system. Animals were intubated and ventilated for 4 hours, at which point they were infected with methicillin-resistant S. aureus strain AW7 via the endotracheal tube, extubated, and then monitored for 96 hours.SettingVentilator-associated pneumonia.SubjectsMale Wistar rats.InterventionsA single application of aerophages prior to ventilation at one of two concentrations (~1010 plaque forming units/mL or ~1011 plaque forming units/mL).Measurements And Main Results1) Animal survival at 96 hours, 2) enumeration of bacteria and phages in the lungs and spleen, and 3) lung tissue histopathology. Animals that received aerophages prior to ventilation and methicillin-resistant S. aureus challenge showed a higher survival rate compared with untreated controls (60% for animals that received 3 × 10 plaque forming units; 70% for animals that received 3 × 10 plaque forming units; 0% for controls; p < 0.01 for each treatment versus untreated). Surviving animals that received aerophage prophylaxis had fewer methicillin-resistant S. aureus in the lungs compared with untreated control animals that succumbed to pneumonia (1.6 × 10 colony forming units/g vs 8.0 × 10; p < 0.01).ConclusionsProphylactically administered nebulized bacteriophages reduced lung bacterial burdens and improved survival of methicillin-resistant S. aureus infected rats, underscoring its potential in the context of ventilator-associated pneumonia.

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