Phage therapy shows promise for Mycobacterium infection

Researchers report 20 new case studies on the use of phage therapy for lethal treatment Mycobacterium Infection, which indicates successful treatment in more than half of patients.

It’s the largest ever set of published case studies of treatment with bacteria-killing viruses known as phages, providing unprecedented detail on their use to treat terrible infections while laying the foundation for a future clinical trial.

“Some of these results are amazing, others are complex,” says Graham Hatfoul, professor of biotechnology at the University of Pittsburgh. “But when we run 20 cases, it becomes more convincing that phages contribute to favorable outcomes – and in patients who have no other alternatives.”

Each patient in the study was seeking care for one or more strains of infection Mycobacterium, a group of bacteria that can cause fatal and treatment-resistant infections in those with compromised immune systems or cystic fibrosis. In 2019, Hatfull led a team that demonstrated the first successful use of sterilants to treat one of these infections.

“For clinicians, this is a real nightmare: It’s not as common as some other infections, but it’s among some of the toughest with antibiotics,” Hatfoul says. “And especially when you take these antibiotics for long periods of time, they are toxic or not very well tolerated.”

Phage therapy

Last month, University of Pittsburgh researchers published two successful studies of treating phage in collaboration with colleagues at National Jewish Health and Harvard University. But these reports represent only a small fraction of the cases the team has been implicated behind the scenes. Since 2019, Hatfull and his lab have sent requests from more than 200 physicians seeking treatments for their patients, working with them to find phages that can be effective against the particular strain of bacteria that infects each patient.

“These are incredibly brave doctors, who have jumped over the edge to conduct an experimental treatment to try to help patients who have no other options,” Hatfall says. “Each of these collaborations represents a sign that can move the field forward.”

Consider measures of patient health and whether samples from the patient still show signs of Mycobacterium After infection, the team found that treatment was successful in 11 out of 20 cases. No patient showed any adverse reactions to the treatment.

In five other patients the results of treatment were inconclusive, and four patients showed no improvement. According to Hatfill, even these obvious failures are key to making the treatment available to more patients. “In some ways, these are the most interesting cases,” he says. “Understanding why they are not working will be important.”

Several unexpected patterns emerged from the case studies. In 11 cases, the researchers were unable to find more than one type of phage that could kill a patient’s infection, although standard practice is to inject a mixture of different viruses so that bacteria are less likely to develop resistance.

“If you had asked me if this was a good idea three years ago, I would have had a seizure,” Hatfall says. “But we did not observe resistance, and we did not see treatment failure from resistance even when only one vacuole was used.”

In addition, the team saw that some patients’ immune systems were attacking the viruses, but in only a few cases their immune systems rendered the virus ineffective. And in some cases, the treatment was still successful despite this immune reaction. Hatfoul says the study paints an encouraging picture for treatment, and opens up the possibility of new phage regimens that clinicians can use to maximize the chance of treatment success.

treatment safety

In addition to the importance of the study for patients facing Mycobacterium infection, and it also represents a major advance in the broader field of phage therapy. The concern in some corners is that researchers may only publish case studies where phage therapy works.

“A series of back-to-back case studies, where we don’t pick the cherries, is a much more transparent way of looking at what works and what doesn’t,” Hatfull says. “This adds a lot of weight to the feeling that the treatment is safe.”

The lab continues to provide phages to more patients — while simultaneously conducting research to expand the funnel that narrowed an initial group of 200 patients to 20, hoping to provide the treatment to more people who have no other options.

“We have not yet figured out how to find or engineer the phages that will transmit each strain of bacteria in these patients,” Hatfoul says. “This is one of the major challenges ahead.”

The paper appears in the magazine Clinical Infectious Diseases.

The study was also led by researchers at the University of California, San Diego.

Source: Patrick Monahan of the University of Pittsburgh

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