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In 2015, Thomas Patterson was on vacation in Egypt with his wife when he first became sick. Unbeknownst to him, he was about to make medical history. Patterson, a professor of psychiatry at the University of California, San Diego, was infected with Acinetobacter baumannii, a pathogen the World Health Organization would later name the most dangerous global pathogen.
Patterson’s condition rapidly deteriorated as he developed acute pancreatitis, septic shock, and multiple organ failure. Despite being flown back to San Diego, conventional FDA-approved antibiotics failed to stop the infection. It was a dire situation until a less conventional treatment came to his rescue: bacteriophage therapy.
A Phage Miracle
Bacteriophages, or phages, are viruses that attack specific bacteria. Patterson’s life was saved by this therapy, administered by Robert “Chip” Schooley, MD, a colleague and friend of the couple. Schooley, a distinguished professor of medicine in the Division of Infectious Diseases at UCSD and co-director of the Center for Innovative Phage Applications and Therapeutics, became the first doctor in the United States to treat a patient with IV bacteriophage therapy for a whole-body bacterial infection.
As antibiotic resistance becomes an escalating global threat, phage therapy is experiencing a renaissance. Historically used before antibiotics were discovered, phage therapy is now being revisited as pathogens like A. baumannii become resistant to conventional treatments.
The Current State of Phage Therapy
Bacteriophages were first discovered over a century ago by microbiologist Felix d’Hérelle. Despite their potential, clinical trials testing their efficacy have been limited. “Most of the phage work being done is outside the context of clinical trials,” Schooley noted. “We don’t have rigorous clinical trials to determine the best doses, routes of administration, immune responses, or what causes phages to lose activity.”
The FDA approved the first U.S. clinical trial on phage therapy in 2019, conducted at UCSD. One of the advantages of bacteriophage therapy is its specificity. Unlike antibiotics, which indiscriminately kill both harmful and beneficial bacteria, phages can target specific bacterial strains without disrupting the entire microbiome.
Phage Preparation
Phages are grown in flasks of live bacteria in labs to ensure they only attack the bacteria causing the illness. They undergo a “lytic” cycle, killing their host bacteria and releasing new phages to infect neighboring bacteria. Previously, separating phages from dead bacteria was challenging due to the risk of harmful toxins, but recent advancements have improved this process.
Getting the right phages is crucial since each phage targets a specific bacterial strain. Developing an effective phage “cocktail” involves extensive testing but can be highly effective when done correctly.
Phage Therapy Is More Important Than Ever
The COVID-19 pandemic shifted focus away from phage research, but the overuse of antibiotics during the pandemic has only heightened the need for alternative treatments. Antibiotic resistance has been exacerbated by overuse in both agriculture and human medicine, leading to a cycle of resistance and drug overuse.
Phage therapy offers a promising solution. Schooley predicts that phages will be used more frequently in the next five years to sterilize infected implant devices, treat recurring infections in people with cystic fibrosis, and even treat urinary tract infections. Phages could also reduce the load of drug-resistant bacteria in the GI tract before chemotherapy or modify the microbiome for diseases caused by specific organisms.
Phage Therapy Going Forward
Schooley and his team at UCSD are actively contributing to phage research, developing and participating in clinical trials sponsored by the National Institutes of Health and commercial entities. They are also making phages available through the FDA’s expanded access program.
However, the perceived lack of profitability of phage therapy has limited funding from large pharmaceutical companies, which prefer to invest in long-term treatments for chronic diseases. This lack of funding hinders the necessary preliminary steps before clinical trials, resulting in smaller studies that may not achieve the most promising results.
Despite these challenges, the potential of phage therapy to combat antibiotic-resistant infections is significant. As antibiotic resistance continues to rise, the need for innovative treatments like phage therapy becomes increasingly urgent.
