Phage therapy for respiratory infections

Abstract

A respiratory infection caused by antibiotic-resistant bacteria can be life-threatening. In recent years, there has been tremendous effort put towards therapeutic application of bacteriophages (phages) as an alternative or supplementary treatment option over conventional antibiotics. Phages are natural parasitic viruses of bacteria that can kill the bacterial host, including antibiotic-resistant bacteria. Inhaled phage therapy involves the development of stable phage formulations suitable for inhalation delivery followed by preclinical and clinical studies for assessment of efficacy, pharmacokinetics and safety. We presented an overview of recent advances in phage formulation for inhalation delivery and their efficacy in acute and chronic rodent respiratory infection models. We have reviewed and presented on the prospects of inhaled phage therapy as a complementary treatment option with current antibiotics and as a preventative means. Inhaled phage therapy has the potential to transform the prevention and treatment of bacterial respiratory infections, including those caused by antibiotic-resistant bacteria.

Keywords: Antibiotic-resistant bacteria; Bacteriophages (Phages); Biopharmaceutics; Formulation; Inhalation; Inhaled phage therapy; Respiratory infection.

Figure 1.

Effect of phage treatment on lethal infection in mice. Mice were treated with PBS (left) or phage solution (right). All mice were infected with bioluminescent Pseudomonas aeruginosa prior to treatment. PAK-P1 phage were given at a phage-to-bacterium ratio of 10:1. Red colour indicates ‘high’ bacterial count and purple colour indicates ‘low’ bacterial count. Figure is adapted from [16].

Figure 2.

Bacterial counts in lung tissue homogenate over time. Mice were treated with phage preparation at 3, 6 and 24 h prior to bacterial challenge. The control group did not receive phage solution prior to infection. Figure is adapted from [61].