Two US patients have recovered from persistent infections after being treated with groundbreaking therapy involving genetically engineered bactericidal viruses.
The cases raise hopes that so-called phage therapy could be used more widely to combat the global crisis of drug-resistant infections. One of the patients, Jarrod Johnson, a 26-year-old man with cystic fibrosis, neared death after a chronic lung infection that resisted antibiotic treatment for six years. After receiving the phage therapy, his infection healed, allowing him to undergo a lung transplant and resume an active life.
“I am so grateful for the effort, perseverance and creativity of all the people involved in my treatment,” said Johnson, who lives in Denver. “I thought I was going to die. They literally saved my life.”
The other patient, a 56-year-old man with severe arthritis, showed remarkable recovery from a skin infection that had gripped his body and was untreatable with conventional drugs. The team, which also developed the groundbreaking treatment for a British teenager four years ago, say the latest cases will pave the way for a clinical trial of phage therapy, which could start next year.
“These two reports really provide substantial encouragement for phage treatments for patients where antibiotics not only fail to control the infections but also contribute substantial toxicity,” said Prof. Graham Hatfull, whose team at the University of Pittsburgh developed the therapies.
Prof Martha Clokie, a microbiologist at the University of Leicester who was not involved in the work, said: “There is a growing sense within the clinical community … that phages may be part of the solution for patients, especially those who really currently have no other alternative option. The overall need for alternatives to antibiotics is enormous.”
In 2019, an estimated 1.2 million people worldwide died as a direct cause of antimicrobial-resistant infections and about 5 million people had a multidrug-resistant infection contributed to their deaths.
Bacteriophages, or phages for short, are harmless viruses that are natural enemies of bacteria. Hatfull has spent nearly four decades collecting a collection of phages, stored in 20,000 frozen vials in his lab. “We have a large collection of phages and we have sequenced more than 4,000 of their genomes so that we understand their genomic profiles and relationships in great detail,” he said.
Since the 2019 UK case, the team has been inundated with requests from doctors who ran out of treatment options for patients. “Then the floodgates opened,” said Dr. Rebekah Dedrick, a research associate in Hatfull’s lab. “We started getting requests from all over the world, and we’re still getting them.”
One of them was Dr. Jerry Nick, director of the adult cystic fibrosis program at National Jewish Health in Denver.
His patient, Jarrod, has cystic fibrosis, a genetic disease that leads to frequent infections that clog the lungs with mucus. By 2020, his lungs were at less than a third of their normal function and he had been plagued by tenacious strains of bacteria for six years. He was turned down for a lung transplant because of the high risk of spreading the infection once he was on immunosuppressants. “In the year before the surgery, he was hospitalized 11 times for a total of 200 days,” Nick says. “He was approaching death and probably still had a year to go.”
In 2016, Nick and his colleagues had sent samples of the Mycobacterium abscessus from Johnson’s lungs to Hatfull’s lab in hopes of finding a phage that could eliminate it. But phages are often specific to only a few types of bacteria, so Hatfull and his team screened dozens of candidates before finally identifying two that efficiently killed the bacteria. They then genetically engineered the phages to increase their efficiency.
Johnson was treated for a little over a year with a combination of phages and antibiotics, requiring two daily intravenous injections, which cleared up the infection and allowed him to undergo a lung transplant. His body developed some antibodies against the phages, but this happened slowly enough for the phages to clear the bacteria, faster than the antibodies that killed the phage.
Since treatment, Johnson has finished high school, worked, met a girlfriend, and although he has had some complications from the transplant, Nick says overall he is doing well.
The second patient, the 56-year-old man with arthritis, developed a serious skin infection, which is a risk in those taking immunosuppressants. He was treated with a single phage called Muddy, which had been discovered in a sample taken from the underside of a decomposed eggplant. After a few weeks, his skin lesions disappeared, and after two months, he tested negative for the bacteria on a biopsy. In total, he was treated for more than eight months.
The cases are described in the journals Cell and Nature Communications.