Old Therapy with a Modern Twist May Reduce the Incidence of Antibiotic-resistant Infections

New research published in the journal Nature suggests that modernized phages therapy may be useful in extending the lifespan of currently available antibiotics and reducing the incidence of antibiotic-resistant infections.

Phages therapy, originally developed by French-Canadian researcher Felix d’Herelle and used extensively in the former Soviet Union, has received renewed attention as antibiotic-resistant infections continue to present a clinical challenge worldwide—an issue that the Centers for Disease Control and Prevention has indicated may soon reach crisis proportions. According to reports in the mainstream press, patients with infections that have proved resistant to currently available antibiotics have even traveled to former Soviet-bloc countries, where phages therapy is still used, to undergo this what’s-old-is-new-again treatment.

“Phage therapy is a potential alternative to antibiotics in certain situations or, as we explored in [our] study, a promising adjunctive therapy where an antibiotic would still be administered but with a bacteriophage that acts synergistically with [it],” explained Benjamin K. Chan, PhD, research scientist in the Department of Ecology and Evolutionary Biology at Yale University and a co-author of the Nature study.

Indeed, Dr. Chan and his colleagues in the lab of Paul. E. Turner, PhD, at Yale isolated a lytic bacteriophage called OMKO1. OMKO1 is part of the Myoviridae family of Pseudomonas aeruginosa and it uses the outer membrane porin M (OprM) of the multidrug efflux systems MexAB and MexXY as a receptor-binding site. They found that OMKO1 produces an “evolutionary trade-off” in multi-drug resistant Pseudomonas aeruginosa. In effect, the team reports, the evolution of bacterial resistance to phage attack changes the efflux pump mechanism, causing “increased sensitivity to drugs from several antibiotic classes,” including ceftazidime, ciprofloxacin, tetracycline, and erythromycin.

“In the strains we studied, we observed a reversal from drug resistance to drug sensitivity due to a forced genetic trade-off,” Dr. Chan told Contagion. “This means that, in theory, drug-resistant bacteria could be treated with the drug it is resistant to in addition to our phage and have a positive clinical outcome.”

The researchers believe that their findings demonstrate that, in some infections—such as those in which bacteria are resistant to all available antibiotics or those in which antibiotic concentration cannot be achieved due to infection site—phage therapy could be a viable alternative to antibiotic use. Dr. Chan emphasizes that the process is “a little more complicated than ‘take this phage cocktail and call me in the morning.’” In fact, the complicated processes involved in phages has perhaps been one of the arguments against its use, historically anyway. However, Dr. Chan noted that he and his colleagues are routinely contacted by patients and their physicians about the prospect of using phage therapy, and many of them have been enrolled in further studies of the approach.

“Depending on application, I do believe that it makes sense to at least consider incorporating phage therapy into clinical practice in certain infections,” Dr. Chan said. “But, it all comes down to the infection type and the route of administration. The phage we described in this publication could be used, in theory, to extend the lifetime of our antibiotic arsenal since it works synergistically with several antibiotics.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.