The University of California San Diego (UCSD) yesterday announced the launch of a new effort to expand the clinical use of bacteria-killing viruses against multidrug-resistant bacterial pathogens.
The Center for Innovative Phage Applications and Therapeutics (IPATH) will bring physicians and researchers from UCSD School of Medicine together to advance research on bacteriophage therapy, in which viruses that specifically target bacteria are used to treat patients with multidrug-resistant infections. The ultimate aim of IPATH will be to make phage therapy more widely available as a clinical option for patients with life-threatening infections that aren't responding to antibiotics.
"The global health crisis of antimicrobial resistance warrants that phage therapy be examined alongside other new drugs that come along," Steffanie Strathdee, PhD, co-director of IPATH and associate dean of global health sciences at UCSD School of Medicine, told CIDRAP News.
Strathdee is a fitting choice to co-lead the center. An epidemiologist by training, Strathdee became an expert in bacteriophages in 2016 when her husband, Tom Patterson, acquired a multidrug-resistant Acinetobacter baumannii infection that left him near death. Strathdee worked with UCSD physicians and phage researchers across the country to have Patterson treated experimentally with an intravenous bacteriophage cocktail after his infection had stopped responding to all antibiotics.
Patterson started improving after a few days of the experimental therapy, and ultimately fully recovered. Since then, UCSD has successfully used bacteriophage therapy on five other patients with severely drug-resistant infections.
"It has to be one of the most exciting experiences of my husband's life and my own, to see that our experience is helping save other lives," Strathdee said.
Focus on clinical trials
Bacteriophage therapy isn't new. In fact, scientists have known for more than a century that certain viruses found in plants, animals, and sewage water can selectively infect and kill specific bacteria.
But interest in bacteriophage research waned with the discovery of antibiotics in the 1940s, and has only now reemerged as antibiotic resistance has begun to limit treatment options. While clinical phage therapy is performed in Eastern Europe and countries of the former Soviet Union, there are no phage therapy products for human use approved in the United States.
One of the focuses of IPATH will be to conduct the type of clinical trials needed for the Food and Drug Administration (FDA) to approve bacteriophage therapy on a wider basis than is currently allowed. As was the case with Patterson, patients seeking phage therapy need to submit an Emergency Investigational New Drug (eIND) application with the FDA. This process allows for use of unapproved, investigational drugs when no other options are available, but only on a case-by-case basis.
Strathdee said she's been "moonlighting as a phage wrangler" ever since the news of her husband's story broke in April 2017, and sometimes gets several calls a day from people seeking her help. But getting emergency bacteriophage therapy is a long process; candidates have to prove they're eligible, the bacterial pathogen that's causing the infection needs to be matched with the right phage from a phage bank, the phages need to be grown and purified, and the patient needs to have a physician who's willing to administer the therapy. It takes a lot of time and staff hours.
The growing demand, and the success of the five other UCSD cases, led Strathdee and Robert Schooley, MD—the lead physician on Patterson's case and the other IPATH co-director—to pursue the idea of starting a bacteriophage-focused research center. They wanted to move beyond using phage therapy as an investigational, emergency treatment. That requires conducting rigorous clinical trials in a wider population of patients.
"That's what's really needed to determine whether or not phage therapy is efficacious in a controlled manner to convince the FDA to approve it as a treatment alongside antibiotic therapy," Strathdee said. "We've seen remarkable successes from these handful of cases, but we're not sure whether or not phage therapy is going to be efficacious in a clinical trial setting."
Adjunct to antibiotics
Strathdee envisions bacteriophage therapy as an adjunct to antibiotic therapy, rather than a replacement. In her husband's case, bacteriophage therapy appeared to work synergistically with antibiotics; a few days after he was injected with the phage cocktail, the infection became susceptible to antibiotics that had previously failed. Strathdee said a similar effect has been observed in some of the other UCSD cases.
"That's the beauty here," she said. "Even if phage therapy wasn't proven to be efficacious in a clinical trial on its own, if it can make a failing antibiotic work better, that's still a game-changer."
The center, which is being launched with the help of a 3-year, $1.2 million grant, will focus on designing and building trials around patients who have multidrug-resistant infections associated with cystic fibrosis, complex urinary tract infections, organ transplantation, and implantable devices like pacemakers. In addition, IPATH will conduct basic research to advance bacteriophage science, and will continue to take eIND cases on a compassionate-use basis.
Jun 21 UCSD Health press release
Nov 16, 2017 CIDRAP News story "To save a life, doctors turn to bacteria-killing viruses"