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Could Old-line Treatments be the Answer to Antibiotic Resistance?

Antibiotic-resistant pathogens continue to make the management of some bacterial infections a significant clinical challenge.

Antibiotic-resistant pathogens continue to make the management of some bacterial infections a significant clinical challenge.

Now, an old-line treatment developed in the former Soviet Union—phage therapy—has emerged as a potential alternative to antibiotics for patients whose infections have failed to respond to a number of interventions. Although the approach has been practiced for decades in the countries that once made up the former Soviet bloc, it has not yet been made widely available in the west, due largely to concerns regarding its safety.

Phage therapy, which is also known as viral phage therapy or bacteriophage therapy, essentially uses bacteria to kill bacteria. Developed by French-Canadian microbiologist Felix d’Herelle, the approach involves the harvesting of bacteria from contaminated water or even animal or human corpses. The bacteria is cultured and applied to cultured samples of the bacteria to be destroyed (ie, the bacteria causing an active infection in a human patient). If the bacteria to be destroyed die following application, the resulting mixture is centrifuged to create a phage solution, which is then tested to see if it causes lysis of the target bacteria. Any phage that causes lysis is then used in treatment.

“There are substantial risks [associated with phage therapy],” David Pride, MD, PhD, associate director of microbiology, University of California-San Diego School of Medicine told Contagion. “Generally, you use the host bacteria to make more phage. The phage must be purified to be free of bacteria and some of their products, otherwise, the risks of giving improper formulations to the patient can be great. There is also the risk of the unknown, in that most of these phage that are delivered have not been completely characterized, so what genes they carry, and are capable of adding to the host’s microbiome, often are unknown.”

Still, according to Dr. Pride and others, the approach is viewed as a viable alternative to antibiotic treatment “in cases of multi-drug resistant (MDR) pathogens.” At present, he added, “it is a therapy of last resort in the US,” and experts say there is limited availability of phages in developed regions such as Western Europe.

However, that may be changing. Experts suggest that the science behind phage therapy, which was most notably used by the Soviets to treat wounded soldiers during World War II, has evolved, and that there is increased understanding of phage evolution and bacterial biology, which could positively impact the safety and efficacy of the approach. A dedicated phage therapy center has been established in the former Soviet republic of Georgia, and clinical trials of the approach are now underway in France, as part of the European Union-funded “phagoburn” project. The approach has been compared to fecal transplant, which is used to treat Clostridium difficile.

“It makes sense to continue to explore alternative approaches such as phage therapy [to treat multi-drug resistant infections],” Dr. Pride noted. “However, there are things that are probably higher priority to prevent the spread of antibiotic resistance, including improved infection practices to prevent the spread of antibiotic resistant organisms, improved antibiotic stewardship practices to prevent the development of these MDR bacteria and research to foster greater understanding of whether these organisms may be harbored in the microbiomes of hospitalized or other individuals and what is their potential for spread.”

Although all of these avenues have been and will continue to be explored, it’s interesting that a Cold War-era intervention may yet hold promise for a solution to a problem that is of growing concern to infectious disease and public health specialists.

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.