In vitro time-kill studies and in vivo efficacy of phage and antibiotic treatments against respiratory Pseudomonas aeruginosa infection

Abstract

Phage and antibiotic combination therapy is a promising approach for treating pulmonary infections caused by multidrug-resistant Pseudomonas aeruginosa, a major pathogen in conditions like cystic fibrosis, bronchiectasis and ventilator-associated pneumonia. Phages are viruses that specifically target and kill bacterial cells, while antibiotics have broad-spectrum activity. When used together, phage-antibiotic synergy can enhance bacterial clearance, lower required antibiotic doses, and reduce the development of resistance. In both in vitro and in vivo studies, phage-antibiotic combinations have shown significant reductions in bacterial load compared to monotherapies. Clinical case reports have also demonstrated the potential of phage therapy, especially in cases where conventional antibiotics fail. Pulmonary delivery methods, such as inhalation via nebulizers or dry powder inhalers, are critical in targeting infections directly in the lungs, enhancing the efficacy of treatments. Despite promising results, challenges remain, including phage resistance, immune response, and regulatory hurdles, which must be addressed through continued research and

clinical trials.