However, Cole’s progress did not last long. His blood infection returned, and his doctors determined that the phage-antibiotic combination was no longer effective. He died of pneumonia in March 2022, seven months after phage therapy was stopped. Cole’s case shows the promise and limitations of phage therapy.
The problem this time is not just the evolution of bacteria. When researchers performed follow-up laboratory tests on Cole’s blood, they found evidence of antibodies to the phages, meaning his immune system was activated, blocking the phages from attacking the bacteria. They suspect phage therapy may have a tipping point, where administering too many phages can trigger an immune reaction that prevents them from working.
Madison Stellfox, an infectious disease postdoctoral researcher at Pitt and lead author of the study, said that what they learned from Cole’s case will help inform how to use phage therapy more effectively going forward, especially as phage clinical trials are underway at Pitt and another place. “From two to four weeks is probably where we get maximum results with phages before the body starts making antibodies against them,” he said. In other words, phages may be better as a short-term treatment.
Two additional patients at other hospitals have been treated with the same phage therapy received by Cole, and one more will soon be treated. About 20 patients overall have been treated with phages at the University of Pittsburgh Medical Center hospitals, and 60 to 70 percent of them have responded to the therapy.
“Infections are complicated,” said Erica Hartmann, a microbiologist at Northwestern University who studies phages and is not involved in Cole’s case. “It’s not as simple as, there’s a criminal and we treat the criminal with whatever weapons we have.”
Persistent bacterial infections are difficult to treat because of the pathogen itself and the conditions within the patient’s body. When a patient has an infection over a long period of time, the bacteria have time to change and adapt. With heavy use of antibiotics, bacteria evolve to avoid their effects. Add to that factors such as a person’s immune system, microbiome, and overall health – all of which influence how well they fight the infection.
Saima Aslam, an infectious disease specialist at the University of California, San Diego and clinical leader of the Center for Innovative Phage Applications and Therapeutics, said one way to avoid phage resistance is to use multiple phages at once to fight the infection.
Bacteria can develop resistance to phages by evolving to have different surface markers, so that the phages no longer recognize them. “Using a combination of three or four phages that have different ways of attaching to bacteria, I think, is one way to overcome development or resistance,” Aslam said. If a bacterium changes so that one phage doesn’t recognize it, others should still recognize it, he said.
Aslam said clinical trials will help provide insight into which patients and types of infections are best suited to phage therapy. His center has treated 18 patients with a success rate of about 80 percent.
While phages are unlikely to replace antibiotics, they could be a powerful tool in fighting drug-resistant bacterial infections – if researchers can figure out how best to use them.
For Mya, Cole’s daughter, the last beach trip with her mother was very special. Although phage therapy didn’t save her, Mya is grateful for the extra time. “I really hope that what my mother tried will help other patients so they can recover,” she said.
2024-02-14 19:18:19
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