Successes of ‘phage therapy’ enhance the fight against drug-resistant infections

Two American patients have recovered from an incurable infection after being treated with a pioneering treatment that includes viruses that kill genetically modified bacteria.

The cases raise hopes that so-called phage therapy could be used more widely to combat the global crisis of drug-resistant infections. One patient, Jarrod Johnson, 26, with cystic fibrosis, was near death after developing a chronic lung infection that had resisted antibiotic treatment for six years. After receiving the phage treatment, his infection was eliminated allowing him to undergo a lung transplant and resume an active life.

“I am so grateful for the efforts, 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 osteoarthritis, showed remarkable recovery from a skin infection that had taken hold of his body and that proved irreversible with conventional medicines. The team, which also developed an innovative treatment for a British teenager four years ago, says these latest cases will pave the way for a clinical trial of the phage therapy, which could begin as soon as next year.

“These two reports really provide great encouragement for phage therapies for patients where antibiotics not only fail to control infection, but also contribute to significant toxicity,” said Professor Graham Hatfull, whose team at the University of Pittsburgh developed the treatments.

Professor Martha Clokey, 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 can be part of the solution for patients, especially with those already at the moment who have no other alternative option.” The overall need for alternatives to antibiotics is huge.”

In 2019, it is estimated that 1.2 million people died globally as a direct cause of antimicrobial resistance, and in approximately 5 million people, multidrug-resistant infections contributed to their deaths.

Phages, in short, are harmless viruses and are natural enemies of bacteria. Hatfull 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 we understand their genetic profiles and relationships in great detail,” he said.

Since the 2019 British case, the team has been inundated with requests from doctors who have exhausted treatment options for patients. “This is the time when the door opened wide,” said Dr. Rebecca Diedrick, a research assistant in Hatfull’s lab. “We’ve started taking requests from all over the world, and we’re still getting those requests.”

One of those was Dr. Jerry Nick, director of the Adult Cystic Fibrosis Program at National Jewish Health in Denver.

His patient, Jarrod, suffers from cystic fibrosis, a genetic disease that results in recurrent infections that clog the lungs with mucus. By 2020, his lungs were performing less than a third of their normal function and he had been plagued by stubborn bacterial strains for six years. He was refused a lung transplant due to the high risk of infection spreading once he was on immunosuppressive medication. “In the year before the operation, he had been hospitalized 11 times for a total of 200 days,” Nick said. “He was close to death and maybe a year left.”

In 2016, Nick and his colleagues sent samples of Mycobacterium abscess From Johnson’s lungs to Hatfull’s lab, in the hope of finding a phage that can kill it. But phages are often specific to only a few types of bacteria, so Hatfull and his team screened dozens of candidates before identifying two that efficiently kill bacteria. They then genetically engineered the phages to enhance their efficiency.

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Johnson was treated with a combination of phages and antibiotics for just over a year, which required two intravenous injections daily, clearing 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, faster than the antibodies killed the phages.

Since treatment, Johnson has finished high school, has been working, met his girlfriend, and although he had some complications from the transplant, Nick overall says he’s doing well.

The second patient, a 56-year-old man with arthritis, developed a serious skin infection, which is a risk among those taking immunosuppressive drugs. It was treated with a single mite, called Muddy, which was detected in a sample taken from the underside of decaying eggplant. After a few weeks his skin lesions were gone and two months later he tested negative for bacteria in a biopsy. It was treated for over eight months in total.

The cases are described in Cell and Nature Communications.

2022-05-13 19:07:00

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