J Infect Dis. 2021 Mar 1:jiab112. doi: 10.1093/infdis/jiab112. Online ahead of print.
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.