Phage therapy shows promise for CF antibiotic-resistant infections…

Bacteriophage therapy could be a promising approach for treating antibiotic-resistant Staphylococcus aureus and Pseudomonas aeruginosa infections in people with cystic fibrosis (CF), according to a small review study.

Scientists believe the review, involving three CF patients and two animal models, support moving forward with clinical trials for bacteriophage therapy in CF, a number of which are currently ongoing.

“The ability to move forward towards human trials and standardise the approach (dosing, duration, route, and use of singular or combination of phages) to using this treatment in CF is on the horizon,” scientists wrote. “However, larger and more robust trials are needed to establish its safety and efficacy and create necessary evidence for global legislative frameworks.”

The study, “A systematic review on the use of bacteriophage in treating Staphylococcus aureus and Pseudomonas aeruginosa infections in Cystic Fibrosis,” was published in Paediatric Respiratory Reviews.

Lung infections can lead to more hospitalizations for patients

The thick, sticky mucus which accumulates in CF lungs provides a breeding ground for bacteria. Lung infections, most commonly caused by S. aureus and P. aeruginosa, are associated with more hospitalizations and lung function declines for CF patients.

While these infections can be treated with antibiotics, certain bacterial strains become antibiotic-resistant, and can’t be killed off with standard approaches. This is in part because they form biofilms, or clusters that embed themselves in a protective matrix.

Bacteriophages, or simply phages, have emerged as a potential way of treating these antibiotic-resistant infections. These viruses selectively replicate in bacteria, leading to bacterial cell death, but don’t target human cells.

There is growing interest in applying phage therapy for lung infections in CF based on preclinical research. While a number of clinical trials are underway, there are few published reports that describe phage therapy in CF patients.

In the report, the scientists conducted a systematic review of studies published between 1942 and 2023 that involve the use of bacteriophages for CF-related S. aureus and P. aeruginosa infections.

Patients were treated through compassionate use programs

Their review ultimately included five studies: three case reports of CF patients and two preclinical studies using CF models. Of the patients, all of whom were treated through compassionate use programs, one was a child and two were adults.

Phage therapy was inhaled, oral, or given as an into-the-vein infusion, and usually included a cocktail of different bacteriophages.

One patient, a 7-year-old girl, saw a complete eradication of both P. aeruginosa and S. aureus after receiving inhaled phage therapy with no adverse side effects.

Another saw a decrease in P. aeruginosa load after phage therapy and the third experienced a change in antibiotic resistance, with  P. aeruginosa infection becoming more sensitive to antibiotics.

Two patients experienced a reduction in pulmonary exacerbations — acute worsening of lung symptoms — and one needed less oxygen supplementation and had lower white blood cell counts. High white blood cell counts indicate active infection.

Phage therapy was not associated with any reported adverse outcomes.

In animals, none of 20 mice experienced a complete eradication of P. aeruginosa, but they did see a decline in bacterial load and a loss of biofilm. Zebrafish also exhibited a 20% decline in bacterial load and exhibited increased survival after phage therapy.

Reductions in inflammatory markers were seen in both animal models.

“This systematic review has shown that early evidence suggests that bacteriophage treatment has potential in the treatment of pseudomonas and staphylococcus aureus in CF with a promising safety profile,” the researchers wrote.

While the advent of CFTR modulator therapies is expected to reduce the number of lung infections requiring antibiotics or phage therapy, there will always be a subset of patients who still need them, the team noted.

Clinical research findings of phage therapy will go beyond CF

Moreover, “while CF patients will be the primary beneficiaries of [bacteriophage therapy], the implications and utility of clinical research within this patient cohort will extend beyond CF in terms of its reach.”

The findings emphasize a need to move from small compassionate use studies to larger clinical trials that will help to establish standard doses, administration routes, and treatment durations.

A number of studies are underway to evaluate phage therapy in CF patients. Phage therapies currently in clinical testing for CF include BiomX’s BX004, Adaptive Phage Therapeutics’ WRAIR-PAM-CF1, and Armata Pharmaceuticals’ AP-PA02, among others.

Such studies will “provide the necessary body of evidence to help establish legislative frameworks globally,” the scientists wrote.