Phage therapy was used for the first time* to treat antibiotic-resistant mycobacterial infection: a cocktail of three bacteriophages, two of which were genetically modified, saved a 15-year-old girl with cystic fibrosis after a double lung transplant.

Chronic lung infections are one of the most challenging issues in the care of patients with cystic fibrosis. This hereditary disease causes the lungs to become filled with mucus, creating ideal conditions for bacterial growth. One of the leading causes of death among patients with cystic fibrosis is chronic antibiotic-resistant Pseudomonas aeruginosa pulmonary infection. We have previously written about the potential of using bacteriophages to treat these patients. Now, bacterial viruses have been successfully used to treat another antibiotic-resistant infection in a patient with cystic fibrosis – Mycobacterium abscessus .

A fifteen-year-old girl with cystic fibrosis, in addition to lung disease, suffered from pancreatic insufficiency, insulin-dependent diabetes mellitus, and liver disease. For eight years, she was prepared for a lung transplant, receiving specific therapy for chronic bacterial infections. The transplant was successful, but several weeks later, while undergoing immunosuppressive and antibiotic therapy, M. abscessus bacteria were detected in her sputum. Her liver function was impaired, her postoperative wound became inflamed, and mycobacterial lesions appeared on her skin.

The M. abscessus infection was resistant to all available antibiotics, so doctors turned to microbiologists from the University of Pittsburgh, who suggested bacteriophage treatment. As is well known, phage therapy requires finding bacteriophages that will specifically target a particular pathogen. To this end, the scientists sent a culture of M. abscessus isolated from the patient to the Bacteriophage Collection at the Howard Hughes Medical Institute. This is one of the largest phage collections in the world, and is being assembled as part of the SEA-PHAGES program with the participation of students from various universities, who "hunt" for phages wherever they can—in water, soil, and air. The collection was essentially created for scientific purposes, and its creators and curators never imagined that it could be directly useful in the treatment of infectious diseases.

R. M. Dedrick et al./Nature Medicine 2019

Three phages specific for M. abscessus —Muddy, ZoeJ, and BPs—were selected from the Collection's samples. Two of these phages interacted weakly with the target bacterium and were genetically modified using the Bacteriophage Recombineering of Electroporated DNA method to enhance their therapeutic potential. In in vitro tests, a mixture of the three phages completely destroyed M. abscessus, even at high concentrations.

The girl was prescribed intravenous bacteriophages every 12 hours for 32 weeks. One month after the start of therapy, topical bacteriophage treatment of skin lesions began. The patient tolerated the treatment well, and bacterial resistance to the phages did not develop during treatment.

M. abscessus was not detected in sputum and blood after the first day of treatment, the girl's condition gradually improved, she began to gain weight, the surgical wound healed, lung and liver function improved, most of the skin lesions (except 2-3) disappeared.

The authors of the article note that this cocktail of bacteriophages is effective only against specific strains of M. abscessus , but if necessary, it is possible to select effective bacteriophages against other pathogens.

Bacteriophages are increasingly helping save lives in people with severe antibiotic-resistant infections. Two bacteriophage-containing drugs have been registered in Ukraine. They target the most common pathogens that cause gastrointestinal and purulent infections, as well as skin, oral, bladder, and ENT infections.

* Dedrick RM, Guerrero-Bustamante CA, Garlena RA et al. Engineered bacteriophages for the treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus // Nature Medicine, 2019, 25: 730-733. DOI: https://doi.org/10.1038/s41591-019-0437-z