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For the first time, researchers have successfully used bacteriophages – bacteria-killing viruses – to treat an antibiotic-resistant mycobacterial lung infection, paving the way for a young National Jewish Health cystic fibrosis patient to receive a transplant of saving lung. The successful use of phages to treat a Mycobacterium abscessus a lung infection was reported in a case study published earlier in the journal Cell.
“We have tried unsuccessfully for years to eliminate mycobacterial infection with a variety of antibiotics,” said Jerry Nick, MD, lead study author and director of the Adult Cystic Fibrosis Program at National. Jewish Health. “When we used the bacteria’s own natural enemies, we were able to eliminate the infection, resulting in a successful lung transplant.”
“I am so grateful for the effort, perseverance and creativity of everyone involved in my treatment,” said Jarrod Johnson, lung transplant recipient. “I thought I was going to die. They literally saved my life.
Cystic fibrosis is an inherited condition that causes thick mucus to build up in the lungs, leading to repeated bacterial infections that damage the lungs and can cause respiratory failure. Although new treatments have greatly improved the prognosis for people with cystic fibrosis, life expectancy is still significantly reduced.
Mycobacteria are a common and widespread genus of bacteria that can cause tuberculosis, leprosy, and non-tuberculous mycobacterial infections (NTMs). Mycobacterium abscessus is a particularly aggressive and difficult NTM infection. Combinations of several antibiotics and treatment extending for a year or more are often unsuccessful. National Jewish Health has the nation’s largest adult cystic fibrosis program and is a leading center for the treatment of NTM infections.
Johnson is a 26-year-old cystic fibrosis patient who suffered from repeated lung infections throughout his life. As a child, he was admitted to various hospitals several times a year. As an adult, he experienced a rapid decline in lung function following a Mycobacterium abscessus infection over a six-year period and received a number of unsuccessful treatments. By 2020, his lung function had fallen below 30%. Without a lung transplant, doctors estimated he was at risk of dying in just a few years.
Johnson had been denied transplants by three transplant centers, primarily due to his mycobacterial infection. Mycobacteria can spread from the lungs to the skin and other tissues, which can infect transplant recipients taking immunosuppressive drugs. Dr. Nick and his team at National Jewish Health considered phages as a potential treatment option. Johnson was hospitalized at Saint Joseph Hospital in Denver, where he spent more than 200 days the year before receiving phage treatment.
Bacteriophages — or phages, for short — are viruses that attack bacteria. Interest in using them to treat bacterial infections has grown in recent years as more and more bacteria have become resistant to antibiotics. Graham Hatfull, PhD, professor of biological sciences at the University of Pittsburgh and author of the study, is a leader in the discovery and use of phages to treat mycobacterial infections, and provided the phages used to treat Johnson.
Phages are often specific to only a few types of bacteria. In 2016, Dr Nick and his colleagues sent samples of the Mycobacterium abscessus Johnson’s lungs looking for a phage that could kill the mycobacterium. Dr. Hatfull and his team in Pittsburgh screened dozens of candidate phages and identified two that effectively killed the mycobacterium infecting Johnson’s lungs. These have been genetically modified to optimize their potential.
Bacteriophages and the “perfect predator”
“This research may serve as a roadmap for the future use of phages to treat patients with severe Mycobacterium abscessus lung infection and to save lives,” said Dr Nick.
Doctors at National Jewish Health have received clearance from the US Food and Drug Administration for compassionate use of the experimental treatment. Johnson received her first phage infusion in September 2020, followed by 500 days of twice-daily infusions. Within two months, various genomic, cell culture and clinical markers indicated that the treatment was successful. Just over a year after starting phage treatment, Johnson’s infection seemed to have cleared up.
Alice L. Gray, MD, medical director of the University of Colorado Lung Transplant Program, deemed the transplant safe now and placed it on the active roster. He received his new lungs in October 2021 at the UCHealth Transplant Center and, working with Dr. Gray, remained on phage therapy throughout the procedure and during his recovery. A range of markers indicated no evidence of infection after the transplant. Johnson has now stopped all treatment for Mycobacterium abscessus and lead a normal life.
Two other successful grave responses Mycobacteria phage infection have been reported by Dr. Hatfull’s team at the University of Pittsburgh. These cases were linked to patients suffering mainly from skin infections. Using phages to treat a wider range of patients will help determine the roles of antibodies and phage resistance, guided by these successful case studies.