For the first time, researchers have successfully used phages — viruses that kill bacteria — to treat an antibiotic-resistant fungal lung infection, paving the way for a young national Jewish patient with cystic fibrosis to receive a life-saving lung transplant. The successful use of sterilants for the treatment of Mycobacterium abscess lung infection was reported in a case study published today in the journal prison cell.
“We’ve tried unsuccessfully for years to clear the fungal infection with a variety of antibiotics,” said Jerry Nick, MD, lead author of the study and director of the Adult Cystic Fibrosis Program at National Jewish Health. “When we used the bacteria’s natural enemies, we were able to clear the infection resulting in a successful lung transplant.”
“I am so grateful for the efforts, perseverance and creativity of all the people who were involved in my treatment,” said Jarrod Johnson, a lung transplant recipient. “I thought I was going to die. They literally saved my life.”
Cystic fibrosis is a genetic disease that causes thick mucus to build up in the lungs, which leads to recurring 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 lower.
Mycobacteria are a common and widespread genus of bacteria that can cause tuberculosis, leprosy, and non-tuberculosis (NTM) fungal infections. Mycobacterium abscess is a particularly aggressive and challenging NTM infection infection. Multiple combinations of antibiotics and treatment spanning 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 treating NTM infections.
Johnson is 26 years old with cystic fibrosis and has had frequent lung infections throughout his life. As a child, he was admitted to various hospitals several times a year. As an adult, he experienced rapid deterioration in lung function after persistent infection with Mycobacterium abscessus over a period of six years and received a number of unsuccessful treatments. By 2020, his lung function had fallen to less than 30%. Without a lung transplant, doctors felt he would likely die in just a few years.
Johnson’s transplants were rejected by three transplant centers, primarily due to a fungal infection. The fungal bacteria can spread from the lungs to the skin and other tissues, which may infect transplant recipients who are taking immunosuppressive medications. Dr. Nick and his team at National Jewish Health considered phages to be a potential treatment option. Johnson was hospitalized at St. Joseph’s Hospital in Denver, where he spent more than 200 days a year before receiving phage treatment.
Phages – 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 Hatfoul, PhD, professor of biological sciences at the University of Pittsburgh and an author on the study, pioneered the discovery and use of phages to treat fungal infections, and introduced the phages used in Johnson’s treatment.
Phages are often specific to only a few types of bacteria. In 2016, Dr. Nick and colleagues sent samples of Mycobacterium abscess from Johnson’s lungs in search of a phage that can kill Mycobacterium. Dr. Hatfull and his team in Pittsburgh examined dozens of candidate phages and identified two bacteria that efficiently killed the mycobacteria that infected Johnson’s lungs. It has been genetically engineered to optimize its potential.
“This research could serve as a roadmap for the future use of sterilants to treat patients with severe B. abscess lung infections and save lives,” said Dr. Nick.
Doctors at National Jewish Health have received FDA clearance to use the experimental treatment in a merciful manner. Johnson received his first dose of phages in September 2020, followed by 500 days of twice-daily injections. Within two months, a variety of genomes, cell cultures and clinical markers indicated the treatment was successful. A little over a year after starting phage treatment, Johnson’s infection appeared to have cleared up.
Alice L. Gray, MD, medical director of the University of Colorado Lung Transplant Program, believes the transplant is now safe and has put him on the active list. He received his new lungs in October 2021 at the UCHealth Transplant Center and, in collaboration with Dr. Gray, continued his phage therapy throughout the operation and during his recovery. A set of markers indicated that there was no evidence of infection after transplantation. Johnson has now stopped all treatments for mycobacterium abscess and is living a normal life.
Two other successful responses to severe fungal phage infection have been reported by Dr. Hatfull’s team at the University of Pittsburgh. These cases were associated with patients suffering primarily from skin infections. The use of phages to treat a broader spectrum of patients will help define the roles of antibodies and phage resistance, guided by these successful case studies.
A single bacteriophage used to treat an immunocompromised patient with an antibiotic-resistant infection
Jerry A. Nick et al, Host and pathogen response to engineered phages against Mycobacterium pneumoniae abscess infection, prison cell (2022). DOI: 10.1016 / j.cell.2022.04.024
Introduction to National Jewish Health
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