Some may find it risky to rub viruses into their wounds, inhale them, swallow them, or even inject them into the bloodstream. But in so-called phage therapy, viruses that actually consume bacteria are actually used, which are harmless to humans.
With the growing number of antibiotic resistances, this long-disused form of therapy is once again receiving more attention. But is it the solution to the great crisis in medicine? Two major German projects are about to treat patients.
Bacteriophages are constantly around us and inside us. An adult is made up of about 30 trillion body cells, 40 trillion bacteria – and 300 trillion phages, says phage therapy expert Christian Willy, director of the Trauma Surgery Clinic at the Bundeswehr Hospital in Berlin. Bacteriophages are viruses that initiate multiplication programs in bacteria until the amount of newly formed viruses causes the bacterial cell to rupture. The accumulation of bacteria, for example in the focus of inflammation, can thus quickly disappear.
Milestone in sight
One of the projects in which patients will soon be treated is “Phage4Cure”, in which therapy is inhalable phages against the dreaded hospital embryo. Pseudomonas aeruginosa is developed. The pathogen often colonizes the lungs of patients with cystic fibrosis. Clinical Phase I of the Basic Compatibility Study is scheduled to begin in late summer, according to Christine Rohde of the Leibniz Institute DSMZ (German Collection of Microorganisms and Cell Cultures GmbH) in Braunschweig. Contrary to what is usual, there is also a direct cohort with patients. “If Phase I is successful and patients feel better, a real milestone for phage therapy in Germany will be reached.”
In Germany, several patients are already being treated for whom the available approved therapies are ineffective. For example, from Christian Kühn, head of the National Phage Center at the Medical Faculty in Hanover. “Every day I see what antibiotic resistance does,” the doctor points out. “We need alternatives.” More than 30 patients have already been treated in Hanover, often against Staphylococcus aureusbacteria that can cause persistent wound infections.
The second major German project, the “PhagoFlow” project, run by the Trauma Surgery Clinic at the Bundeswehr Hospital in Berlin, is also based on individual production used for each individual patient – known as a master application. While “Phage4Cure” is about the clinical picture, the pathogen and the administered mixture, “PhagoFlow” is designed to treat different clinical pictures resulting from different pathogens, as explained by project manager Willy. From the second half of the year, the first patients could be treated, he hopes.
Long known as penicillin
Bacteriophages have been used to fight infections for about a hundred years. They were discovered a good ten years before Scottish bacterial researcher Alexander Fleming discovered the antibiotic effects of penicillin in 1928.
The big difference between these two bacterial killers: While antibiotics act more like a weapon of mass destruction, phages are contract killers with a very specific purpose. They always attack only one type of bacteria, very often only one specific strain of a certain type, which complicates their use: First, it is necessary to find a suitable phage for the relevant bacterial strain of the patient. “And more than one strain usually plays a role in critical infection,” explains Holger Ziehr, head of pharmaceutical biotechnology at the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM).
But where to find suitable phages to fight a specific pathogen? Experts often choose a very simple source: “wastewater,” says phage researcher Alexander Harms of the Biozentrum at the University of Basel. First, the bacteria against which the phages are to be used are cultured on nutrient plates. The water sample comes to the bacterial turf. If a phage killing the bacteria is present, a hole will form in the bacterial turf – the virus will isolate from this place and multiply in the laboratory.
Much more effort than pulling a pill out of a drawer that works against many pathogens. But miraculous antibiotic weapons are in danger of becoming boring. It is estimated that more than 30,000 deaths in the EU each year are caused by antibiotic-resistant bacteria. There are an estimated 700,000 of them worldwide. The upward trend. Can phage therapy help?
In Eastern bloc countries – where there was initially no access to antibiotics – phages continued to be used frequently. Institutions from such countries are still world leaders, especially the Georgi Eliava Institute in Tbilisi, Georgia. Other countries such as the USA, Belgium and France are now renewing this form of therapy. Examples from the USA show that today it is possible to create a suitable phage therapy for a patient within 10 days, says Christian Kühn from the phage center in Hanover.
Convincing results on phage efficacy in very large clinical trials, as they have become a required standard in drug research, are not yet available for phages, which can often only be used individually, says phage expert Christine Rohde. As German experts explain, individual case reports and smaller studies have shown impressive success.
In a recently presented study, 20 patients with insoluble bacterial infections were treated with bacteriophages. The therapy was successful in eleven patients, the researchers reported in the journal “Clinical Infectious Diseases”. Accordingly, no side effects occurred. Ziehr refers to a heterogeneous group of participants that included children and adults with different clinical pictures, complex infections, and different types of pathogens. The fact that more than half of the participants responded to the therapy in these circumstances is impressive, says the expert, who did not take part in the work.
As experts point out, bacteriophages do not completely replace antibiotics. A combination of bacteriophages and antibiotics, based on the so-called phage-antibiotic synergy (PAS), could be a promising path, explains Willy, a phage researcher in Berlin. It has been shown that in a patient previously treated with phage, resistant bacteria can become sensitive to antibiotics again.
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