When Antibiotics Don’t Work
Phages help with “nightmare” transitions

6/11/2022, 4:56 PM

Increasingly, bacterial pathogens no longer respond to antibiotics. Then sometimes phage therapy can help, as one study showed. Clinical trials are currently being prepared in Germany.

Phage therapy can help fight difficult-to-treat bacterial infections. In one study, an international research team treated a total of 20 patients using so-called bacteriophages – viruses that kill bacteria. All participants had extremely stubborn bacterial infections. The therapy was successful in eleven patients, reports the group led by Graham Hatfull from the University of Pittsburgh in the specialist journal “Clinical Infectious Diseases”, Accordingly, there were no side effects.

Holger Zeiher, head of pharmaceutical biotechnology at the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM) in Braunschweig, refers to the extremely heterogeneous group of participants in the study, which included both children and adults with different clinical pictures, complicated infections and a variety Were. of pathogens. Given these circumstances, it is impressive that more than half of the participants responded to therapy, say experts, who were not involved in the work. “This result cannot be argued.”

phage causes bacteria to multiply

Bacteriophages are viruses that infect bacteria. Some phages are specific on different types of bacteria, often only on certain strains of one type. Viruses enter the bacteria through specialized receptors and multiply in the cell – until the mass of the newly produced virus causes the bacterial cell to burst and thus kill it.

Because of their extreme specialization, bacteriophages do not destroy any beneficial bacteria during therapy, for example in the intestines, and they also do not attack body cells. On the other hand, a suitable phage has to be found for the specific pathogen strain of a patient. While phage therapy has a long tradition in the former Eastern Bloc countries, it has fallen into disuse in Western countries after the advent of antibiotics.

This has been changing for many years—particularly because of the increasing resistance of bacterial pathogens to antibiotics. study leader Hutful did in the past Study the matter Each with promising results – in patients where all previous approaches had failed. He then questioned doctors about 200 patients around the world.

antibiotic resistant mycobacteria

From this, the team selected 20 participants who were infected with so-called mycobacteria, mostly strains of the species Mycobacterium abscissus. 16 patients had the metabolic disease mucovyzidose, also known as cystic fibrosis (CF). Because of a genetic defect, mucus can no longer drain through many organs, such as the lungs. This allows bacteria to nest and cause inflammation, among other things.

Hatful said in a statement to his university that Mycobacterium abscission infections are a nightmare for doctors. “Although they are not as common as some other infections, they are the most difficult to treat with antibiotics.”

Participants, including adults and children over the age of five, received varying phases by injection or inhalation, mostly one billion units twice a day for six months. The team described the therapy as successful in eleven subjects, found no improvement in four patients, and the outcome was inconclusive in the remaining five.

No side effects seen

Doctors found no evidence that the pathogens had become immune to the phage during therapy. In addition, he did not notice any side effects. “This gives considerable weight to the notion that the therapy is safe,” Hatful says.

It is not clear why the treatment worked for some and not others. Hatful says it may have something to do with the phages used. “We have not yet figured out how to find or create phages that capture each strain of these patients. This is one of the major challenges for the future.”

In Germany, a clinical study on phage therapy should begin in the second half of the year, says Zeiher, a Braunschweig phage specialist. This – in contrast to the current study – is a fairly similar group of participants therefore exclusively CF patients infected with the lung germ Pseudomonas aeruginosa. You get a cocktail of three different phases that is about 75 percent P. aeruginosa strains. Zeehar expects the first results during the coming year.