Antimicrobial resistance, in which germs like bacteria and fungi no longer respond to medicines, is a rising global threat. When antibiotics and other drugs become ineffective, infections can become difficult or impossible to treat, leading to an increase in the spread and severity of disease.

In a study published in Nature Medicine, a team of researchers at the Centre for Phage Biology and Therapy at Yale discovered a novel approach that may revolutionise the fight against antimicrobial resistance.

For the study, the research team investigated the use of phage therapy—the use of viruses, or phages, to target and kill bacteria—to help patients with cystic fibrosis, a disease in which antimicrobial resistance is a significant issue. The team pioneered a strategy to select phages that not only kill bacteria that cause infections but also weaken surviving bacteria to become less virulent or less resistant to antibiotics.

The study found improved lung function, reduced sputum P. aeruginosa—one of the most prevalent infection-causing bacteria in cystic fibrosis—and evidence of phage-resistant bacteria having reduced pathogenicity in the nine adults treated with this therapy. The therapy was safely delivered by nebulisation.

There are millions of people worldwide who are suffering from drug-resistant infections, said Jon Koff, MD, associate professor in Yale School of Medicine's Section of Pulmonary, Critical Care, and Sleep Medicine (Yale PCCSM) and medical director of the Center for Phage Biology and Therapy, who is the corresponding author of the study.

"We currently have a lack of effective antibiotics, and the World Health Organization predicts that by 2050, we'll have more deaths from antimicrobial resistance than from chronic diseases like cancer and diabetes," he said.

"This compassionate treatment is an opportunity for us to use phage therapy for patients with life-threatening infections and no other treatment options."

Paul Turner, Ph.D., Rachel Carson Professor of Ecology and Evolutionary Biology and director of the Centre for Phage Biology and Therapy, emphasised Koff's understanding of the capability of infecting bacteria to evolve resistance to administered phages.

"He continues to advocate that personalised treatments and clinical trials in phage therapy must address this possible limitation, so that evolved phage resistance in bacteria is either minimised or steered down a path which coincides with reduced pathogenicity, thus improving patient outcomes," Turner said.

The study highlights the power of Yale's integrated basic, translational, and clinical science teams, said Naftali Kaminski, MD, Boehringer Ingelheim Pharmaceuticals, Inc. Professor of Medicine and chief of Yale PCCSM.

"Addressing microbial drug resistance is a critical unmet need, and the team at the Centre for Phage Biology and Therapy at Yale is at the frontline of this battle," he said.

Members of the research team have had conversations with the U.S. Centres for Disease Control and Prevention and the Cystic Fibrosis Foundation about setting up centres for phage therapy around the U.S. The Centre for Phage Biology and Therapy at Yale is poised to lead the way in developing a U.S.-based system of coordinated care for patients who need compassionate treatment, Koff said.

The goal is to develop partnerships across and beyond Yale to treat patients locally and to develop a standard that can be used nationwide, he said.

In addition, the team is working with countries in Europe and South America to establish national phage therapy programs.

"When we look at the trajectory of antimicrobial resistance, we see a pandemic that could happen in the next 30 years," Koff said. "By using phage therapy to help patients with cystic fibrosis, we are also finding solutions to address a growing crisis."