Center for Innovative Phage Applications and Therapeutics (IPATH)

A new Nature study found that rifaximin, an antibiotic commonly used to treat liver disease, causes resistance to daptomycin, one of the few drugs that is effective against vancomycin-resistant enterococcus: https://lnkd.in/d_aRbyZH

The Pride Lab Team is on the red carpet at the San Diego International Film Festival. We were in attendance to watch the Australian Film "Last Chance to Save a Life", a documentary about the trials and tribulations of a group of patients and scientists using phages as an experimental treatment against multi-drug-resistant bacterial infections. Beyond succinctly presenting phages and phage therapy, Director Emma Watts chronicled the emotions scientists and patients experience when dealing with the reality of incurable infections. As one of the researchers working toward making phage therapy a reality, I cannot stress how important the role of science communication is in the visibility of the issue and long term funding toward a solution. If you are curious about phages or someone who is into documentaries, I would highly recommend watching "Last Chance to Save a Life". Big thanks to the Center for Innovative Phage Applications and Therapeutics (IPATH) for sponsoring the event and inviting our team.

So giving phages via the blood is difficult. Oral dosing has its challenges. How else can you get them into the body? What about the lung? Delivering phages through the airways? There are multiple bacterial infections of the lung which can be targeted. In particular there are those affecting patients with cystic fibrosis where bacterial infection of the lungs is a major problem. Pseudomonas aeruginosa infections are a particular concern, Delivering by a nebuliser, generating an aerosol of the drug, is often used for lung delivery, and has been used for viral agents delivering gene therapy. Could that work for phages? Yes, it could. Phages can be optimized to survive the aerosolization process, allowing delivery to the deep lung. There are challenges, especially in cystic fibrosis, where the lung becomes clogged with mucus, but it is possible to deliver phages. Even though bacteria within the lung can be targeted directly via the airways, some groups have targeted them with phages delivered via the blood, which has had some success in individual cases. But this adds extra challenges to effective treatment. And even aerosolization might not be required? Given that the airways can be heavily colonized by the target bacteria, it could be possible to deliver phages to the upper airways, relying on phages multiplying within the airways to achieve delivery to the deep lung. So why are there no phage drugs on the market yet? Well, they are coming, and clinical trials are advancing. But, as always, it takes time. See: Aslam S et al (2024). Pseudomonas aeruginosa ventricular assist device infections: findings from ineffective phage therapies in five cases. Antimicrob Agents Chemother.  68: e0172823. BioMX (2023). https://lnkd.in/eBBFG6Dv Golshahi L et al (2011). In vitro lung delivery of bacteriophages KS4-M and ΦKZ using dry powder inhalers for treatment of Burkholderia cepacia complex and Pseudomonas aeruginosa infections in cystic fibrosis. J Appl Microbiol.; 110: 106-117. Ling KM, Stick SM, Kicic A (2023). Pulmonary bacteriophage and cystic fibrosis airway mucus: friends or foes? Front Med (Lausanne); 10: 1088494. Nick JA et al (2022). Host and pathogen response to bacteriophage engineered against Mycobacterium abscessus lung infection. Cell; 185: 1860-1874.e12. Rappo U (2023). Nebulized Phage Therapy for Patients with Cystic Fibrosis with Chronic Pseudomonas aeruginosa Pulmonary Infection: A Phase 1b/2a Randomized, Double-Blind, Placebo-Controlled, Multicenter Study. Open Forum Infect Dis.; 10(Suppl 2): ofad500.2474. #bacteriophage #phage #delivery #lung #cystic_fibrosis #CF #inhaled #aerosolised drh@thephageadviser.com