Eradication of Pseudomonas aeruginosa using fixed-dose combination of probiotics and bacteriophages: development of an inhalable powder

Psuedomonas aeruginosa is a common respiratory pathogen, with increasing drug-resistant strains, posing significant challenges. As antibiotic development slows, alternatives such as probiotics and bacteriophages are being explored. Probiotics which are widely used in the food industry for their antimicrobial properties, have recently demonstrated efficacy in reducing P. aeruginosa in cellular and murine models. Bacteriophages have shown clinical success against multidrug-resistant infections and are more efficacious when combined with antibiotics. This study investigated the potential interaction between probiotics and bacteriophages in controlling P. aeruginosa growth. Species-dependent effects were observed, with combinations ofLactobacillus reuteriorL. salivariuswith phage PEV1 capable of eradicating P. aeruginosa in vitro. These combinations were formulated into inhalable powders via spray drying using varying ratios of leucine and either lactose or trehalose. Viability of both probiotics and phages was influenced by probiotic species, sugar type, and sugar:leucine ratio. Fine particle fractions ranged from 31 to 51%, and bactericidal activity of the combinations was retained post-processing. This is the first study to explore the potential synergistic interaction of two biological agents and to successfully formulate a fixed-dose combination of probiotics and phage into an inhalable powder. While both components are considered safe individually, further studies are required to confirm any synergistic effects and to evaluate the safety of their combined use in the lungs.