Bacteriophages (green) attacking a bacterium (orange). [Image courtesy of Graham Beards]
Bacteriophages (green) attacking a bacterium (orange). [Image courtesy of Graham Beards]

As Human Phage Therapy Day (April 27) approaches, a collaborative team of researchers led by investigators at the University of California San Diego (UCSD) School of Medicine is preparing to present data about the successful treatment of a patient near death from a multidrug-resistant bacterium using an experimental therapy involving bacteriophages. The scientists and clinicians will present their findings today—at the Centennial Celebration of Bacteriophage Research at the Institute Pasteur in Paris—in a talk entitled “Intravenous Application of Phage Therapy to Treat a Terminally Ill Patient Who Was Infected with Multi Drug Resistant A. baumannii.”

The investigators are hopeful that this case study could be a catalyst to developing new remedies to the growing global threat of antimicrobial resistance, which the World Health Organization estimates will kill at least 50 million people per year by 2050. Based on the success of this case, UCSD is exploring options for a new center to advance research and development of bacteriophage-based therapies.

The story began in late 2015, when Tom Patterson, Ph.D., a 69-year-old professor in the department of psychiatry at UCSD School of Medicine, and his wife, Steffanie Strathdee, Ph.D., chief of the division of global public health in the department of medicine, were spending the Thanksgiving holiday in Egypt and Patterson became ill, wracked by abdominal pain, fever, nausea, vomiting, and a racing heartbeat. Local doctors diagnosed pancreatitis, but standard treatment didn't help.

Dr. Patterson's condition worsened, and he was medevacked to Frankfurt, Germany, on December 3, 2015, where physicians discovered a pancreatic pseudocyst, a collection of fluid around the pancreas. The fluid was drained and the contents cultured. Patterson had become infected with a multidrug-resistant strain of Acinetobacter baumannii, an opportunistic and often deadly pathogen. The bacterium has proved particularly problematic in hospital settings in the Middle East, with many injured veterans and soldiers returning to the U.S. with persistent infections.

“When it became clear that every antibiotic had failed, that Tom could die, we sought an emergency investigational new drug application from the FDA to try bacteriophages,” explained lead study investigator Robert “Chip” Schooley, M.D., professor of medicine, chief of the Division of Infectious Diseases at the UC San Diego School of Medicine and primary physician on the case.

“To our knowledge, he is the first patient in the United States with an overwhelming systemic infection to be treated with this approach using intravenous bacteriophages,” Dr. Schooley added. “From being in a coma near death, he's recovered well enough to go back to work. Of course, this is just one patient, one case. We don't yet fully understand the potential—and limitations—of clinical bacteriophage therapy, but it's an unprecedented and remarkable story, and given the global health threat of multidrug-resistant organisms, one that we should pursue.”

Scientists and physicians at University of California San Diego School of Medicine, working with colleagues at the U.S. Navy Medical Research Center (NMRC), Texas A&M University, a San Diego-based biotech, and elsewhere, have successfully used an experimental therapy involving bacteriophages—viruses that target and consume specific strains of bacteria—to treat a patient near death from a multidrug-resistant bacterium. [UCSD]

Bacteriophages are ubiquitous viruses, found wherever bacteria exist. It's estimated there are more than ten million trillion trillion (1031) bacteriophages on the planet—more than every other organism on Earth, including bacteria, combined. Each is evolved to infect a specific bacterial host to replicate without affecting other cells in an organism. The idea of using phages therapeutically is not new. Described a century ago, phage therapy was popular in the 1920s and 1930s to treat multiple types of infections and conditions, but results were inconsistent and lacked scientific validation.

With dwindling options, the UCSD team went looking for help and found many researchers willing to help. Moreover, with emergency approval from the FDA, each source provided phage strains to UC San Diego doctors to treat Dr. Patterson, with no guarantee that any of the strains would work.

“That's one of the remarkable things to come out of this whole experience,” remarked Dr. Schooley. “The incredible and rapid collaboration among folks scattered around the world. It was a desperate time, and people really stepped up.”

While phage therapy is typically administered topically or orally, in Dr. Patterson's case, the phages were introduced through catheters into his abdominal cavity and intravenously to address a broader, systemic infection, which had not been done in the antibiotic era in the U.S. “That makes them more effective,” said Dr. Schooley. “The action is at the interface of the patient and the organism.”

In early May, Dr. Patterson was taken off of antibiotics. After June 6, there was no evidence of A. baumannii in his body. He was discharged home August 12, 2016.

While the researchers were excited by their findings and the outcome, they know that any broad, future approved application of phage therapy faces fundamental challenges, unlike past treatments.

“What the FDA is used to saying is 'This is an antibiotic. We know what its structure is and how you can give it to multiple people,'” Dr. Schooley stated. “With bacteriophage therapy, the FDA would be dealing with an approach in which doctors would have to develop phage cocktails for each patient tailored to their infecting organisms. It's the ultimate personalized medicine.”

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