Two US patients have recovered from intractable infections after being treated with a pioneering therapy involving genetically engineered bacteria-killing 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, was approaching death after suffering a chronic lung infection that resisted treatment by antibiotics for six years. After being given the phage therapy, his infection cleared allowing him to receive a lung transplant and resume an active life.
“I am so grateful for the effort, persistence and creativity of all the people who were involved in my treatment,” said Johnson, who lives in Denver. “I thought I was going to die. They have literally saved my life.”
The other patient, a 56-year-old man with severe arthritis, showed a remarkable recovery from a skin infection that was taking hold of his body and which had proved untreatable with conventional drugs. The team, who also developed the breakthrough treatment of a British teenager four years ago, say these latest cases will pave the way for a clinical trial of phage therapy, which could launch as soon as 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 feeling within the clinical community … that phages could be part of the solution for patients, especially with those that really at the moment have no other alternative option. The overall need for alternatives for antibiotics is huge.”
In 2019, 1.2 million people are estimated to have died globally as a direct cause of antimicrobial resistant infections and in about 5 million people, a multi-drug-resistant infection contributed to their death.
Bacteriophages, phages for short, are harmless viruses that are natural enemies of bacteria. Hatfull has spent nearly four decades amassing a collection of phages, stored in 20,000 frozen vials in his lab. “We’ve got a large collection of phages, and we’ve sequenced over 4,000 of their genomes, so we understand their genomic profiles and relationships in exquisite detail,” he said.
Since the 2019 British case, the team has been inundated with requests from doctors who had run out of treatment options for patients. “That’s when the floodgates opened,” said Dr Rebekah Dedrick, a research associate in Hatfull’s lab. “We started to get requests from around the world, and we still get them.”
One of these was Dr Jerry Nick, director of the adult cystic fibrosis programme at National Jewish Health in Denver.
His patient, Jarrod, has cystic fibrosis, a genetic disease that results in frequent infections clogging up the lungs with mucus. By 2020, his lungs had less than a third of their normal function and he had been plagued by a stubborn bacterial strains for six years. He was rejected for a lung transplant due to the high risk of the infection spreading once he was on immunosuppressant drugs. “In the year before the operation, he was admitted to hospital 11 times and for 200 days in total,” said Nick. “He was approaching death and probably had a year left.”
In 2016, Nick and his colleagues had sent samples of the Mycobacterium abscessus from Johnson’s lungs to Hatfull’s lab in the hope of finding a phage that could eliminate it. But phages are often specific for 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 boost their efficiency.
Johnson was treated with a combination of the phages and antibiotics for just over a year, requiring two daily intravenous injections, which cleared the infection, allowing him to have a lung transplant. His body developed some antibodies against the phages, but this happened slowly enough that the phages were able to get rid of the bacteria, quicker than the antibodies killed off the phage.
Since treatment, Johnson has finished high school, been working, met a girlfriend and although he has had some complications from the transplant, overall Nick says he is doing well.
The second patient, the 56-year-old man with arthritis, developed a serious skin infection, which is a risk among those on immunosuppressive drugs. He was treated with a single phage, called Muddy, which had been discovered in a sample taken from the underside of a decomposed aubergine. After a few weeks his skin lesions cleared and after two months he tested negative for the bacteria on a biopsy. He was treated for more than eight months in total.
The cases are described in the journals Cell and Nature Communications.
