Virus Therapy Saves Patient With An Antibiotic-Resistant Infection

Here's how the viruses called bacteriophages attack and kill bacteria such as E. coli and P. aeruginosa that can cause deadly infections.

Sources: Centers for Disease Control and Prevention; National Institutes of Health; World Health Organization

Researchers said they treated a 15-year-old patient's antibiotic-resistant infection with the help of genetically engineered viruses. The effort points to a potential path for countering the growing threat of bacteria resistant to antibiotics.
 The researchers, in the U.S. and the United Kingdom, saved the patient with the help of bacteria-destroying viruses known as bacteriophages that occur naturally and are the most populous organisms on the planet. Using genetic engineering, the researchers tweaked some of the phages to specifically fight the patient's infection.
 The effort, published Wednesday in the journal Nature Medicine, marked the first reported use of genetically engineered phages to treat a patient, researchers said. The success suggests promise for using engineered phages more broadly against antibiotic-resistant bacteria.
 “We have to be cautiously optimistic about clinically individual cases,” said Helen Spencer, a pediatric respiratory consultant at Great Ormond Street Hospital for Children in London who treated the patient.
 “But I think in terms of globally what we're facing in terms of antibiotic resistance, this could be a really important therapy.”
 Antibiotic resistance is a growing threat across the globe, as overuse of antibiotics in hospitals and in farm animals has made some bacteria resistant and increasingly dangerous, said Helen Boucher, an infectious-disease specialist at Tufts Medical Center in Boston.
 About 23,000 people die from drug-resistant infections in the U.S. each year, according to the Centers for Disease Control and Prevention, and drug resistant infections could kill as many as 10 million people a year by 2050.
 Clinicians first started experimenting with phage therapy to treat bacterial infections as early as 1919, though it fell out of practice in the West after the widespread introduction of antibiotics. The therapy has remained in use in some countries in Eastern Europe and the former Soviet Union.
 Now researchers in Western countries are once again exploring phage therapy as bacteria become increasingly resistant to classic antibiotics and new antibiotics are slow to enter the market.
 Academic institutions, biotech companies and clinical trials with a focus on bacteriophages are popping up across the U.S., and a handful of patients have been successfully treated with the experimental therapy.
 The 15-year-old patient, who had cystic fibrosis, had been taking antibiotics for eight years to fight off two persistent strains of bacteria. After a lung transplant for her cystic fibrosis, however, the infection spread and stopped responding to the antibiotics.
 As a result, the girl's liver lost function; she stopped eating and drinking and had visible lesions on her skin. Looking for new options to treat the patient, Dr. Spencer turned to phage therapy. She partnered with a team at the University of Pittsburgh that had amassed a library of over 15,000 different phages from across the world in order to find one that would attack the patient's infections.  

Researchers used genetically engineered viruses to treat a 15- year-old girl.

 The team focused their search on 1,800 phages both that matched the type of bacteria of the patient's infections and whose genetic makeup was known. They found three phages—from Pittsburgh, Providence, R.I., and Durban, South Africa—but only one of the matching phages would actually eliminate the infection.
 That is because, while some phages reproduce within their bacterial hosts and then bust them open, others replicate with the bacteria without harming it, according to Robert Schooley, a professor of medicine in the division of infectious diseases at the University of California, San Diego and a senior author on the case.
 The researchers used genetic engineering to remove a gene that prevents the phages from killing the bacteria, turning them into bacteria destroyers, said Graham Hatfull, a professor of biological sciences at the University of Pittsburgh and a senior author on the paper. Dr. Spencer then administered the three-phage cocktail to the patient—both intravenously and directly applied to her skin—in addition to a few antibiotics.
 The patient healed gradually over six months. The patient is still actively receiving both antibiotic and phage treatment to stave off the infection while otherwise living a relatively normal life, according to Dr. Spencer.  



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