Combining a phage cocktail with antibiotics improves recovery from Pseudomonas-induced VAP in mice

Ventilator-associated pneumonia (VAP) poses a severe threat in hospital settings, particularly with the rise of multidrug-resistant bacteria like carbapenem-resistant Pseudomonas aeruginosa. Recognized as "critical priority" bacteria by the WHO, these pathogens demand innovative solutions. Our study explores the potential of bacteriophage (phage) therapy as a compelling intervention for VAP. Previously, we showed that even repetitive injections of a P. aeruginosa phage cocktail elicited only a marginal immune response in naïve mice.

To assess its therapeutic efficacy, we induced P. aeruginosa-VAP in wild-type mice through high-tidal-volume ventilation, triggering ventilator-induced lung injury, followed by intratracheal infection with P. aeruginosa strain PaO1. Therapy efficacy of the P. aeruginosa-specific phage cocktail, meropenem, or a combination of both via two intraperitoneal administrations was compared.

At 24 hpi, the combination therapy effectively reduced the bacterial load up to 3 logs in BAL and lungs, as did meropenem, but showed minimal inflammation and even faster recovery of the mice than under phage cocktail therapy. The clinical score decreased with increasing body temperatures as early as 16 hpi, whereas meropenem-treated mice did not reach normal levels until 24 hpi. Moreover, inflammatory mediators and lung permeability were reduced, but not immune cells in alveolar spaces after phage treatment.

In conclusion, our findings propose the synergistic potential of a specific phage cocktail combined with antibiotic treatment as a promising avenue for managing VAP infections caused by P. aeruginosa. This dual approach not only effectively combats the bacterial load, but also contributes to a swifter recovery with reduced inflammation.