At a Glance Commentary Scientific knowledge on the subject Antibiotic resistance challenges current practice. New antimicrobials approved for clinical application are scarce, and this underscores the urgent need for alternative strategies. Phage therapy is a promising approach for the treatment of antibiotic resistant bacteria, however infection specific, proof-of-concept experimental studies are currently missing. What this study adds to the field We assessed the efficacy of phage therapy for the treatment of experimental ventilator associated pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) in rats. Phage treatment improved survival compared to placebo and was equally as effective as traditional antibiotics in controlling MRSA infection. Combination of phages with antibiotics did not further improve outcome in this experimental setting.

Background The optimal method for delivering phages in the context of ventilator-associated pneumonia (VAP) is unknown. In the current study, we assessed the utility of aerosolized phages (aerophages) for experimental MRSA pneumonia. Methods Rats were ventilated for 4h before induction of pneumonia. Animals received either: 1) aerophages; 2) intravenous (IV) phages; 3) a combination of IV and aerophages; 4) IV linezolid; and 5) a combination of IV linezolid and aerophages. Phages were administered at 2, 12, 24, 48 and 72h, and linezolid at 2, 12, 24, 36, 48, 60 and 72h. The primary outcome was survival at 96h. Secondary outcomes were bacterial and phage counts in tissues, and histopathological scoring of the lungs. Results Aerophages (1) and IV phages (2) each rescued 50% of animals from severe MRSA pneumonia (P<0.01 compared to placebo controls). The combination of aerophages and IV phages rescued 91% of animals, which was higher than either monotherapy (P<0.05) (3). Standard-of-care antibiotic linezolid (4) rescued 38% of animals. Linezolid and aerophages (5), however did not synergise in this setting (55% survival). Conclusions Aerosolized phage therapy showed potential for the treatment of MRSA pneumonia in an experimental animal model and warrant further investigation for application in humans.

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