The case report of a cystic fibrosis (CF) patient suggests that phages — viruses that naturally infect and kill bacteria — are a potential personalized therapy against infections caused by antibiotic-resistant bacteria.
The study, “Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus,” was published in the journal Nature Medicine.
Patients with CF frequently have long-lasting bacterial infections in the airways. Sometimes, these bacteria are resistant to antibiotics, which makes them difficult to manage.
Antibiotic-resistant bacteria pose a particular risk to CF patients undergoing lung transplant, because they can flare during the immunosuppression period required as part of the transplant procedure.
Now, a team of researchers reported the case of a 15-year-old girl with CF who had a flare caused by antibiotic-resistant bacteria after lung transplant, and who was successfully treated with a new therapeutic approach based on phages.
The patient had recurrent infections with bacteria of the genus Mycobacterium for eight years, and had less than a third of a normal lung function by the time she received a double lung transplant at Great Ormond Street Hospital in London.
Some weeks after the transplant, the doctors noticed that the site of the surgical wound was red. Further, the patient showed signs of infection in the liver, and developed bacterial nodules — packages of bacteria that grow underneath the skin — in her arms and legs. The infection did not respond to traditional antibiotics.
Her doctors then considered using phages as a potential treatment to resolve the infection. They sent a sample of the bacteria infecting the girl to Graham Hatfull, PhD, a Howard Hughes Medical Institute professor at the University of Pittsburgh, who runs a program called SEA-PHAGES, which specializes in collecting, storing, and studying different phages found in the environment.
Hatfull’s team tested different phages from the collection to see if one, or some of them, could specifically target the bacteria infecting the patient. They found three phages that showed some specific antibacterial activity.
The team used these three to prepare a “phage cocktail.” Researchers edited the genome of two of the phages to improve their antibacterial properties. They also removed a gene that allows viruses to reproduce inside bacteria without causing any harm — without this gene, phages break the bacterial cells, destroying them.
Hatfull sent the phage cocktail to London, where it was given intravenously (through the vein) to the patient twice daily for at least six months. A billion phage particles were present in every dose.
The surgical wound started to heal a month after beginning the phage-based treatment. The patient’s liver and pulmonary function improved after six weeks, and almost all the skin nodules had disappeared after six months.
The patient did not show any harmful side effects or produce an immune response against the treatment. So far, there are no signs of bacteria resistant to the phage cocktail.
“To our knowledge, this is the first therapeutic use of phages for human mycobacterial infection, and the first use of engineered [genetically modified] phages,” the researchers said.
“The idea is to use bacteriophages as antibiotics — as something we could use to kill bacteria that cause infection,” Hatfull said in a press release.
“We are sort of in uncharted territory, but the basics of the young woman’s case are pretty simple, we purified the phages, we gave them to the patient, and the patient got better,” Hatfull added.
According to the researcher, a phage-based approach holds the potential for providing personalized treatment against drug-resistant bacteria in CF patients. It also has potential for use against other types of bacterial infections associated with other diseases, like tuberculosis, he said.