When antibiotics don't work: phages help with "nightmare" infections

Increasingly, bacterial pathogens no longer respond to antibiotics.

When antibiotics don't work: phages help with "nightmare" infections

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

Phage therapy can help fight difficult-to-treat bacterial infections. In a 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 group from the University of Pittsburgh in the journal "Clinical Infectious Diseases". Accordingly, 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 heterogeneous group of participants in the study, which included both children and adults with various clinical pictures, complex infections and different types of pathogens. The fact that, given these circumstances, more than half of the participants responded to the therapy is impressive, says the expert, who was not involved in the work. "This result cannot be argued away."

Bacteriophages are viruses that infect bacteria. Certain phages are specialized on individual types of bacteria, often only on certain strains of a type. The viruses penetrate the bacteria via special receptors and multiply in the cell - until the mass of newly produced viruses causes the bacterial cell to burst and thus kill it.

Due to 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 must be found for the specific pathogen strain of a patient. While phage therapy has a long tradition in former Eastern Bloc countries, it has fallen into disuse in Western countries following the advent of antibiotics.

This has been changing for several years - in particular because of the increasing resistance of bacterial pathogens 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 then received inquiries from doctors about around 200 patients worldwide.

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

Mycobacterium abscessus infections are a nightmare for doctors, Hatfull is quoted as saying in a statement from his university. "Although they are not as common as some other infections, they are among the most difficult to treat with antibiotics."

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

The doctors found no evidence that pathogens became immune to the phages during the course of therapy. In addition, they observed no side effects. "That 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, says Hatfull. "We haven't yet figured out how to find or make phage that will catch every strain of these patients. That remains one of the key challenges for the future."

In Germany, a clinical study on phage therapy should begin in the second half of the year, says the Braunschweig phage expert, Ziehr. This - in contrast to the current study - quite 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 in the course of the coming year.

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