However, Cole's progress did not last long. Her blood infection returned and her doctors determined that the combination of phages and antibiotics was no longer effective. She died of pneumonia in March 2022, seven months after discontinuing phage therapy. Cole's case illustrates both the promise and limitations of phage therapy.
The problem this time was not just bacterial evolution. Researchers ran follow-up tests on Cole's blood and found evidence of antibodies to the phage. This means that her immune system was activated and blocked the phages from attacking the bacteria. They suspect there may be some kind of tipping point for phage therapy, where too much can trigger an immune response and interfere with its function.
Madison Stelfox, an infectious disease postdoctoral fellow at Pitt and the study's lead author, said the lessons learned from Cole's case will be important going forward, especially as phage clinical trials are underway at Pitt. They say this will help us learn how to use phage therapy more effectively. And elsewhere too. “Probably the most effective time to treat phages is two to four weeks, before the body starts producing antibodies against them,” she says. In other words, phages may be a good short-term treatment.
Since then, two more patients at other hospitals have received the same phage therapy as Cole, and a third patient is about to receive the treatment. A total of about 20 patients across the University of Pittsburgh Medical Center hospitals have been treated with phages, and 60 to 70 percent of them responded to the treatment.
“Infectious diseases are complex,” says Erica Hartman, a microbiologist at Northwestern University who studies phages. She is not involved in Cole's case. “It's not as simple as saying there's a bad guy and we use every weapon in our arsenal to deal with that bad guy.”
Persistent bacterial infections are difficult to treat due to the pathogen itself and the patient's internal state. If a patient has been infected for a long time, the bacteria have time to change and adapt. When antibiotics are used frequently, bacteria evolve to counteract their effectiveness. Add to this factors such as a person's immune system, microbiome, and overall health, all of which influence how well they can fight infections.
Saima Aslam, an infectious disease expert and clinical director of the Center for Innovative Phage Applications and Treatments at the University of California, San Diego, says one way to avoid phage resistance is to use multiple phages at once against an infection. states that it is to use.
Bacteria can develop resistance to phages by evolving different surface markers, making them unable to recognize them. “I think one way to overcome outbreaks and resistance is to use a combination of three or four that have different ways of attaching to bacteria,” Aslam says. Even if the bacterium changes so much that one phage doesn't recognize it, other phages should, she says.
Aslam said clinical trials will help determine which patients and types of infections are most suitable for phage therapy. At her center she has treated 18 patients, with a success rate of about 80%.
Phages are unlikely to replace antibiotics, but if researchers can find the best way to introduce them, they could become a powerful tool in the fight against drug-resistant bacterial infections.
For Cole's daughter Maia, her last beach trip with her mother was special. Although her phage therapy didn't save her, Mia is grateful for her extra time. “I'm very hopeful that what her mother was able to experiment with will help other patients heal,” she says.