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.

Phage-Antibiotic Combination Treatments: Antagonistic Impacts of Antibiotics on the Pharmacodynamics of Phage Therapy?

“…These involve phages infecting bacteria lethally and, in the process, producing new bactericidal agents, i.e., new phage virions. Phages have been employed clinically to treat bacterial infections for roughly one-hundred years [1,2], and many of these efforts seem to have been successful, e.g., such as in terms of treatment of chronic infections [3,4], wound infections [4][5][6], or lung-associated infections [7][8][9][10]. This 'phage therapy' furthermore has been proven to be efficacious in at least one modern efficacy (phase I/II) clinical trial [11], and recently there have been several well publicized phage therapy case-study successes [12][13][14]; see also [4,9,10,[15][16][17].…”

The global preclinical antibacterial pipeline

“…Patient-specific phage cocktails allow the use for rare pathogens, whereas recombinant lysins may cover a broader spectrum of Gram-negative bacteria. Although phages have been used historically in topical formulations (mostly skin) 43 , phage preparations are being developed for intravenous, aerosol or diverse locally applied formulations 44 . The immense size of phages compared with small-molecule antibiotics poses pharmacokinetic challenges, and important scientific questions remain regarding availability at the site of infection and determining the best dosing regimen 45 .…”

Steps to address anti-microbial drug resistance in today’s drug discovery

“…However, the delivery of phage particles, which are comprised of proteins and nucleic acids (and sometimes lipids) can provoke an antibody response which precludes repeated dosing [11]. Alternative delivery strategies using the respiratory route could solve some of these issues [12].…”