But Cole’s growth was short-lived. The infection returned in his blood, and his doctors determined that the phage-antibiotic combination was no longer effective. She died of pneumonia in March 2022, seven months after phage therapy stopped. Cole’s case shows both the promise and the limitations of phase therapy.

This time the problem was not just bacterial evolution. When the researchers ran follow-up lab tests on Cole’s blood, they found evidence of antibodies against the phage, meaning his immune system had been activated in a way that prevented the phage from attacking the bacteria. They suspect that phage therapy may have a tipping point of sorts, where giving too much of it can trigger an immune response that stops it from working.

Madison Stilfox, a postdoctoral fellow in infectious diseases at Pitt and lead author of the study, says what she learned from Cole’s case could help inform how phage therapy can be used more effectively. should be used, especially when phase-in clinical trials are underway. and elsewhere. “Two to four weeks is probably where we get the most benefit for our deer with phages before the body starts making antibodies against them,” she says. In other words, phages may be better as a short-term treatment.

Two additional patients at other hospitals have since been treated with the same phase of therapy that Cole received, and a third is about to be treated. A total of about 20 patients have been treated with phage at the University of Pittsburgh Medical Center hospitals, and 60 to 70 percent of them have responded to the therapy.

“Infections are complicated,” says Erica Hartman, a microbiologist at Northwestern University who studies phages and was not involved in Cole’s case. “It’s not as simple as there’s a bad guy and we deal with the bad guy with whatever weapon we have.”

Treatment of persistent bacterial infections is difficult due to the pathogen itself and the conditions in the patient’s body. When a patient has a prolonged infection, the bacteria have time to change and adapt. With heavy use of antibiotics, bacteria evolve to counteract their effects. Add to these factors such as a person’s immune system, microbiome, and overall health—all of which influence how well they are able to fight off infection.

Saima Aslam, an infectious disease specialist at the University of California, San Diego and clinical lead of the Center for Innovative Phage Applications and Therapeutics, says that one way to avoid phage resistance is to use multiple phages simultaneously against the infection. go

Bacteria can develop resistance to phage by adapting to different surface markers, so the phage can no longer recognize it. “I think using a combination of three or four that have different ways of binding to bacteria is one way to control development or resistance,” Aslam says. If the bacteria mutate in such a way that one phage can’t recognize it, the others still should, she says.

Aslam says clinical trials will help shed light on which patients and what types of infections might be best for phase therapy. His center has treated 18 patients with an almost 80 percent success rate.

Although phages are unlikely to ever replace antibiotics, they could be a powerful tool in combating drug-resistant bacterial infections—if researchers can figure out how to use them. Is.

For Cole’s daughter Maya, her last trip to the beach with her mom was a special one. Although the phage therapy didn’t save her, Maya is grateful for the extra time. “I’m very hopeful that the tests my mom was able to do will be helpful to other patients so they can get better,” she says.