The enemy of our bacterial enemy can indeed be our friend. In a new case report, doctors say they were able to treat their patient’s long-festering, drug-resistant infection with the help of specially grown bacteriophages — viruses that infect bacteria. Large-scale clinical trials will likely be needed for these treatments to become widely used, though.
Viruses hijack the cells of living things to make more of themselves. And just as there are viruses that specifically infect humans, plants, and other organisms, there are some that have evolved to prey on bacteria. It wasn’t long after scientists discovered the existence of viruses at the turn of the 20th century that they learned about phages, too. And by the late 1910s, some doctors were already trying to exploit phages as a potential treatment against bacterial infections, which came to be known as phage therapy.
But by the 1940s, with the advent of the modern antibiotic era, phages had fallen out of favour for several reasons. The first antibiotics that saw wide use were broad-spectrum, able to quickly treat many different types of infections, and relatively easy to scale up in mass production. Phages, on the other hand, were harder to purify and store, and their benefits were often inconsistent.
Scientists and doctors in some parts of the world where antibiotics were less available, such as Eastern Europe and India, did continue to research and use phage therapy, though. And eventually, it became clear that antibiotics weren’t quite as miraculous as we’d hoped. Bacteria have evolved resistance to these drugs over time, to the point where we’re now seeing infections that can’t be treated at all. So, understandably, scientists have expressed renewed interest in phages as a weapon against bacteria in recent decades.
This new report, published Tuesday in the journal Nature Communications, details a 30-year-old woman in Belgium who had been living with a superbug infection for nearly two years. The woman had been gravely injured during the March 2016 Brussels bombing, and after surgery to repair a broken femur, she contracted a series of bacterial and fungal infections. Four months into continued antibiotic treatment, doctors confirmed that she carried a strain of Klebsiella pneumoniae, a common hospital-associated germ that was extensively resistant to antibiotics. The infection also seemed to become part of a biofilm, a hardy, sticky layer of bacterial colonies that clump together, making it even harder for antibiotics to succeed. The infection made it impossible for her pus-filled wound and her injuries to fully heal.
By November 2016, after months of unsuccessful attempts to clear the K. pneumoniae infection, her doctors had cleared the use of phage therapy with the hospital’s ethics committee. The specially selected phages were provided by the George Eliava Institute of Bacteriophages, Microbiology and Virology, in Tbilisi, Georgia. But her treating physicians disagreed about the best course of action for treatment, and the phase therapy was postponed while she continued to take antibiotics.
Finally, in February 2018, fearing a “therapeutic dead end,” her doctors went ahead and decided to use the phages. The phages were given to her after a surgical procedure to remove dead tissue from the wound and to replace the frame that kept her broken bone stable. She was also given bone grafts that had been infused with antibiotics. Over the next six days, she would receive the phages through a catheter. Midway through, she was also switched to a newer antibiotic thought to be more effective against the superbug.
By day two of the combination phage and antibiotic treatment, the infection at last seemed to be retreating. And by the three-month mark, the infection had fully cleared and the woman was taken off antibiotics altogether. Three years in, she’s now able to regularly participate in sporting events like cycling, though she does require a crutch for aid at times. Most importantly, “there are no signs of recurrent K. pneumoniae infection,” the doctors wrote.
The findings appear to show that phages can be used in sync with antibiotics to treat otherwise incurable infections, though they may also be useful on their own. In this case, the phages were “pre-adapted” to the infection, meaning that the phages were repeatedly exposed to the bacteria, each time picking up mutations designed to make them even deadlier. This process is thought to improve their potency and reduce the risk of bacteria learning how to outsmart the phages.
While phage therapy is experiencing a resurgence in medicine, there are still many questions about the best way to take advantage of them. Even experts excited about the potential of phages say that more research is needed to secure their widespread acceptance by doctors.
“Really, the future of phage therapy does rest upon abundant data from clinical trials,” Paul Turner, a professor of ecology and evolutionary biology at Yale University not affiliated with the research, told Livescience.
There are already ongoing trials of phages testing them out in treating hardy superbug infections, such as those that tend to affect people with conditions like cystic fibrosis.