Totto Pastime received her M.Sc. from the National Institute of Virology India. She is currently completing a project in Sweden and is eager to understand more about virus-host interactions
A glimpse at the potential of phage therapy in tackling antibiotic resistance
As we showed you in a previous article on Infective Perspective, antibiotic resistant hospital-associated infections are on the rise. You can check out this short film to learn more about the mounting problem of drug resistance. Recent news regarding a 70 year old Nevada woman, who died from an infection resistant to all antibiotics in the US, is worrisome. When I read the news in the beginning of 2017, I immediately scrolled up and down to read the general public’s reactions. Sure enough, an author from the same magazine tweeted back his own article providing the plan to tackle drug-resistant infections compiled by Jim O’Neill and his team. The report includes several recommendations to solve the problem, one of which is to increase financial support (via the Global Innovation Fund) to fund early-stage infection research to supply more drugs. More opportunities for microbes to develop resistance.
New drugs can work as therapy or prevention and come in many shapes and sizes. As someone majoring in virology, though, I am most intrigued by a little-known antibacterial called phage therapy. This therapy uses a type of virus called bacteriophage (which literally means “bacteria eater”), to target pathogenic bacteria, infect, and kill them. Microbiologists began enthusiastically to practice this type of medicine in the early 1920s and 1930s, but excitement waned after World War II, when antibiotics were discovered and took over modern medicine. Stephen T Abedon and colleagues wrote a thorough review of the history of phage therapy in the western world. The review also outlines many benefit of phages as antibacterial agents, but it appears that most countries have neglected this mode of treatment in favor of antibiotic pills. There is one major exception: the Soviet Union.
Russia, Georgia and Poland produce phages for local clinical use as well as well as for the military. This happened because they had less access to antibiotics (for political and financial reasons at the time antibiotics first entered the market) and phages offered a cheap, effective alternative. Moreover, today, they continue the use of phage therapy for medical tourism in which many patients fly across the world to receive this type of therapy in Tbilisi, Georgia.
For the rest of the world, with the significant concern of antibiotic resistance, it is worth looking for alternatives when all other marketed antibacterial treatments fail, as they did for the woman who recently died in Nevada. But has phage therapy ever been used elsewhere?
A former R&D director of a private diagnostics company that focuses on bacterial tests, Drew Smith, has responded in online Q&As on why phage therapy has not taken off in most parts of the world. He listed lack of interest from pharma companies and financial backup as the top reasons for phage therapy’s absence in the modern western market. There is also the issue of regulation; regulating antibiotic use is easy because every pill of a given drug is chemically identical to the next. Phages, however, are dynamic entities whose populations will change (naturally or artificially) to target specific bacterial species. Current FDA-like regulations therefore make it difficult to manage so-called “dynamic” therapies, and the introduction of phage therapy to a western market would require novel policy considerations. But on a brighter note, almost two years ago the EU funded a clinical trial on phages to assess its international standards. The PhagoBurn project is the largest phage project today and consists of partners and researchers from France, Switzerland and Belgium.
One of the groups involved in the PhagoBurn project is Pherecydes Pharma, located in France. The company recently released some good news on the project. In their latest publication, they reported success when combining phages and antibiotics to treat Pseudomonas aeruginosa infections. P. aeruginosa is a bacterial species that has an ability to develop resistance to antibiotics quite rapidly and is known to be very difficult to treat, especially in individuals suffering from cystic fibrosis. There are several antibiotics that have activity against this pathogen, and one of them is called ciprofloxacin. The researchers from Pherecydes found that the combination of Pseudomonas-infecting phages with ciprofloxacin resulted in synergy to increase efficacy in clearing P. aeruginosa infections.
So far with this outcome, it seems that efforts in combating antibiotic resistance using phages are not completely unfeasible, nor are they particularly expensive. Although the technology is considered relatively outdated, with the advent of gene editing phages can be patented and manipulated to target highly specific bacterial strains for an even more targeted therapy than the average broad-spectrum antibiotic. This could serve as a way to attract big industries to fund more research in the field.