When Antibiotics Don’t Work: Phages help with “nightmare” infections.

When antibiotics don’t work
Phages help with “nightmare” infections.

Increasingly, bacterial pathogens no longer respond to antibiotics. So sometimes phage therapy can help, as one study shows. A clinical investigation is currently being prepared in Germany.

Phage therapy can help fight hard-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 Graham Hatfull’s team of the University of Pittsburgh in the journal Clinical Infectious Diseases. As a result, there were no side effects.

Holger Ziehr, Head of Pharmaceutical Biotechnology at the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM) in Braunschweig, refers to the extremely diverse group of study participants, which included both children and adults with various clinical pictures, complex infections and different types of pathogens. In light of these circumstances, it is striking that more than half of the participants responded to the therapy, says the expert, who was not involved in the work. “This result cannot be denied”.

Phages cause bacteria to explode

Bacteriophages are viruses that infect bacteria. Some phages specialize on single types of bacteria, often only on certain strains of one type. Viruses enter bacteria through special receptors and multiply in the cell, until the mass of newly produced viruses causes the bacterial cell to explode and then the kills.

Due to their extreme specialization, bacteriophages do not destroy any beneficial bacteria during therapy, for example in the intestine, and also do not attack the cells of the body. On the other hand, it is necessary to find a suitable phage for a patient’s specific pathogen strain. Although phage therapy has a long tradition in former Eastern Bloc countries, it has fallen out of use in Western countries following the advent of antibiotics.

The situation has changed for several years, in particular due to the increasing resistance of pathogenic bacteria to antibiotics. In the past, study leader Hatfull had published individual case studies with promising results, each in patients for whom all previous approaches had failed. He has therefore received inquiries from doctors on around 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 Mycobacterium abscessus species. 16 patients had mukoviszidose metabolic disease, also called cystic fibrosis (CF). Due to a genetic defect, mucus can no longer drain from many organs such as the lungs. This allows the bacteria to nest and cause inflammation, among other things.

Mycobacterium abscessus infections are a doctors’ nightmare, Hatfull is said to have said in a statement from his university. “While they are not as common as some other infections, they are some of the most difficult to treat with antibiotics.”

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

No side effects observed

Doctors found no evidence that the pathogens became immune to phages during the course of therapy. Furthermore, they did not observe any side effects. “This gives considerable weight to the impression that the therapy is safe,” says Hatfull.

It is unclear why the treatment worked for some and not for others. This may have something to do with the phages used, Hatfull says. “We still haven’t figured out how to find or create phages that capture each strain of these patients. This remains one of the key challenges for the future.”

In Germany, a clinical trial of phage therapy is expected to begin in the second half of the year, says Braunschweig phage expert Ziehr. This – contrary to the current study – a fairly uniform group of participants is therefore exclusively CF patients who are infected with the lung germ Pseudomonas aeruginosa. You get a cocktail of three different phages that cover about 75 percent of P. aeruginosa strains. Ziehr expects the first results over the next year.

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