Experimental Phage Therapy Saves Patient With Multidrug-Resistant Bacterial Infection

Ancient viruses kill Acinetobacter baumannii

Scientists and physicians at the University of California–San Diego (UCSD) School of Medicine, working with colleagues at the U.S. Navy Medical Research Center (NMRC), Texas A&M University, 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 infection.

The investigators say the case study could be a catalyst to developing new treatments to fight the growing global threat of antimicrobial resistance, which the World Health Organization estimates will kill at least 50 million people per year by 2050.

Derived from the Greek words meaning “bacteria eater,” bacteriophages are ancient and abundant—found on land, in water, and in any form of life harboring their targets. Phages cause a trillion trillion successful infections per second and destroy up to 40% of all bacterial cells in the ocean every day.

Thousands of varieties of phage exist, each evolved to infect only one type or a few types of bacteria. Like other viruses, they cannot replicate by themselves, but must commandeer the reproductive machinery of bacteria. To do so, they attach to a bacterium and insert their genetic material. Lytic phages then destroy the cell, splitting it open to release new viral particles to continue the process. Phages, therefore, may be considered the only “drug”’ capable of multiplying; when their job is done, they are excreted by the body.

The unique case study began in late 2015. Tom Patterson, PhD, a 69-year-old professor in the Department of Psychiatry at the UCSD School of Medicine, and his wife, Steffanie Strathdee, PhD, chief of the Division of Global Public Health in the Department of Medicine, were spending the Thanksgiving holiday in Egypt when Patterson became ill, wracked by abdominal pain, fever, nausea, vomiting, and a racing heartbeat. Local doctors diagnosed pancreatitis, but standard treatment didn’t help.

Patterson’s condition worsened, and on December 23 he was medevacked to Frankfurt, Germany, where doctors 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.

Initially, the only effective antibiotics proved to be a combination of meropenem, tigecycline, and colistin, a drug of last resort because it often causes kidney damage, among other adverse effects. Patterson’s condition stabilized sufficiently for him to be airlifted from Germany to the intensive care unit at Thornton Hospital at UCSD. Upon arrival, it was discovered that his bacterial isolate had become resistant to all of these antibiotics. His abdomen had swelled, distended by the pseudocyst teeming with multidrug-resistant A. baumaunnii. His white blood cell count had soared—a sign of rampant infection.

Patterson’s doctors tried various combinations of antibiotics. He developed respiratory failure and hypotension that required ventilation and recurrent emergency treatment. He became increasingly delirious. When he lapsed into a coma in mid-January, he was essentially being kept alive on life support.

On March 15, 2016, Patterson began receiving bacteriophage therapy consisting of a cocktail of four phages provided by Texas A&M and the San Diego-based biotech company AmpliPhi pumped through catheters into the pseudocyst. If the treatment didn’t kill him, Patterson’s medical team planned to inject the NMRC’s phages intravenously, flooding his bloodstream to reach the infection raging throughout his body. As far as Patterson’s doctors knew, such a treatment had never been tried before.

On March 17, the NMRC’s phages were injected intravenously. There were fears about endotoxins naturally produced by the phages. No one knew what to expect, but Patterson tolerated the treatment well—there were no adverse effects—and on March 19, he suddenly awoke and recognized his daughter.

Subsequent treatment wasn’t easy, however, and the learning curve was steep. There were bouts of sepsis. Despite improvement, Patterson’s condition remained precarious. His doctors discovered that the bacterium eventually developed resistance to the phages, but the team compensated by continually tweaking treatment with new phage strains—some that the NMRC had derived from sewage—and antibiotics.

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

Recovery has not been entirely smooth. There have been setbacks unrelated to the phages. A formerly robust man, Patterson had been fed intravenously for months in the hospital and had lost 100 pounds, much of it muscle. He has required intense physical rehabilitation to regain strength and movement. Nonetheless, he describes his experience as miraculous.

Source: UCSD Medical School; April 25, 2017.