Phage therapy successes bolster fight against drug-resistant infections


Two American patients have recovered from refractory infections after being treated with a pioneering therapy involving genetically engineered bacteria-killing viruses.

These 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 on the verge of death after suffering from a chronic lung infection that resisted antibiotic treatment for six years. After receiving phage therapy, her infection cleared up, allowing her to receive a lung transplant and resume an active life.

“I am so grateful for the effort, perseverance and creativity of everyone 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 taken hold of his body and which had proven incurable with conventional medication. The team, who also developed the breakthrough treatment for a British teenager four years ago, say these latest cases will pave the way for a clinical trial of phage therapy, which could be launched as early as next year.

“These two reports really provide substantial encouragement for phage treatments for patients in whom antibiotics not only fail to control infections but also contribute to substantial toxicity,” said Professor Graham Hatfull, whose team from the University of Pittsburgh developed the therapies.

Professor 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 who are really at the moment have no other alternative option. The global need for alternatives to antibiotics is enormous.

In 2019, an estimated 1.2 million people died worldwide as a direct cause of antimicrobial resistant infections and in about 5 million people, a multi-drug resistant infection contributed to their death.

Bacteriophages, or phages for short, are harmless viruses that are the 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 have a large collection of phages and have sequenced over 4,000 of their genomes, so 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 had run out of treatment options for patients. “That’s when the floodgates opened,” said Dr. Rebekah Dedrick, a research associate at Hatfull’s lab. “We started getting requests from all over the world, and we’re still getting some.”

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 condition that leads to frequent infections that clog the lungs with mucus. In 2020, his lungs had less than a third of their normal function and he had been plagued by a stubborn strain of bacteria for six years. He was rejected for a lung transplant due to the high risk of spreading the infection once on immunosuppressive therapy. “The year before the operation he was hospitalized 11 times and for a total of 200 days,” Nick said. “He was near death and he probably had a year left.”

In 2016, Nick and his colleagues sent samples of the Mycobacterium abscessus Johnson’s lungs to Hatfull’s lab in hopes of finding a phage that could eliminate him. But phages are often only specific for a few types of bacteria. Hatfull and his team therefore examined dozens of candidates before identifying two that effectively killed bacteria. They then genetically modified the phages to increase their effectiveness.

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Johnson was treated with a combination of phages and antibiotics for just over a year, requiring two daily intravenous injections, which cleared up the infection, allowing him to have a lung transplant. His body developed antibodies against the phages, but this happened slowly enough that the phages were able to get rid of the bacteria, faster than the antibodies killed the phage.

Since treatment, Johnson has finished high school, is working, has 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 in people on immunosuppressive drugs. He was treated with a single phage, called Muddy, which had been discovered in a sample taken from under a decomposed eggplant. After a few weeks his skin lesions disappeared and after two months he tested negative for the bacteria in a biopsy. He was treated for more than eight months in total.

The cases are described in the journals Cell and Nature Communications.


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