The study, published in the journal Microbes and Infection, suggests that carefully designed combinations of bacteriophages, antibiotics and antifungal drugs, given in the right order, can break down some of the toughest microbial communities seen in hospitals.
The work is led by Dr. Bartłomiej Grygorcewicz from the Pomeranian Medical University in Szczecin, northwestern Poland.
His team focuses on infections linked to so-called biofilms, slimy, multi-layered communities of microbes that cling to medical devices and tissues and shield bacteria and fungi from both drugs and the immune system.
These infections are a growing concern as antibiotic resistance rises worldwide.
The World Health Organization has warned that the development of entirely new classes of antibiotics has slowed sharply in recent decades, while bacteria that resist many or almost all available drugs, sometimes called “superbugs,” are spreading in hospitals and the wider community.
Bacteriophages, often shortened to “phages,” are viruses that infect and destroy specific bacteria but leave human cells alone. They occur naturally and can be selected in the laboratory to attack particular bacterial strains.
“Choosing an effective phage takes days or weeks, not decades as in the case of a new antibiotic,” Grygorcewicz said in an interview with Poland's PAP news agency. He added that phages can be combined into “cocktails,” so therapy can still work if bacteria become resistant to a single virus.
The new study looked at infections caused by a pair of well-known hospital pathogens that often appear together. One is the all too common bacterium Staphylococcus aureus, or golden staph, and the other is Candida albicans, a fungus. Together they can form mixed biofilms that are especially difficult to treat.
Biofilms tend to grow on catheters, implants, post-surgical wounds, and in the airways of some patients.
“Biofilms are extremely difficult structures to destroy,” Grygorcewicz said. Even if an antibiotic reaches the inside of this protective matrix, some cells switch into a dormant state and become insensitive to treatment.
“That is why infections of this kind can last for months or return after an apparent improvement,” he added.
On their own, phages were effective against the bacterial part of the biofilm, but they did not clear the entire mixed structure that also contained fungi.
The strongest results came when phages were combined with an antibiotic and an antifungal drug.
“The best effects come from joining phages with antibiotics and antifungal medicines. A well-chosen combination works much more effectively than any of these agents used alone,” Grygorcewicz explained.
The team tested many different combinations of the three elements and also changed the order in which they were given. In a liquid model that mimics infections in blood or lymph, the most effective sequence began with bacteriophages.
An antifungal drug followed, and an antibiotic came last. In this order, both bacteria and fungi were controlled most efficiently.
In mature biofilms, which are more resistant to treatment than free-floating microbes, the picture looked slightly different. The best results came either when all three agents were applied at the same time or when phages and an antibiotic were given together first, followed by the antifungal drug.
According to the authors, this suggests that timing matters as much as the choice of drugs.
Grygorcewicz stressed that phages do not act as carriers for medicines. Instead, they weaken bacteria and disturb the structure of the biofilm. In some cases, they damage bacterial cells in a way that helps antibiotics and antifungal drugs penetrate more deeply.
In other situations, an antibiotic can even increase phage multiplication inside the bacteria, which strengthens the viral attack.
“We observed that when a bacteriophage is used first, it loosens the biofilm structure. This makes it easier for the next drugs to reach hidden microorganisms,” he said.
The research points to one of the major challenges in bringing phage therapy into everyday practice. Each phage attacks only a narrow range of bacteria, sometimes just a single strain.
This precision helps protect beneficial bacteria in the body, for example in the gut, but it also means that treatment has to be tailored for each patient. Doctors must identify the microbe causing the infection, and laboratories must select and combine suitable phages.
A few countries have already begun to integrate phage therapy into modern medicine in a more systematic way.
Belgium has created a framework known as the “magistral phage” model, in which phages are treated like custom-made medicines prepared by pharmacists for individual patients on the basis of a doctor’s prescription.
A sample from the patient is used to identify the culprit bacterium, and then matching phages are selected and mixed into a phage cocktail for use in hospital.
Georgia has a long tradition of phage therapy, and clinics in countries such as Australia and the United States have also started experimental treatments.
In Poland, phages are still used only in experimental settings, including at the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences in the southwestern city of Wrocław.
According to Grygorcewicz, the main obstacle to wider use is the lack of clear legal rules at European Union level. At present, there is no unified EU regulation describing how phage preparations should be made, tested and prescribed for human patients.
Grygorcewicz is a co-founder of the Polish Society for Research on Viruses of Microorganisms, which brings together scientists working on phages and related topics. The association organizes conferences, encourages cooperation between research centers, and supports the development of phage research in Poland.
“This is a subject that attracts huge interest worldwide,” Grygorcewicz said. He believes that discoveries about how to combine phages with standard drugs, and how to use them in complex infections such as biofilms, may help doctors in the future when current medicines fail.
He warned that growing resistance to antimicrobial drugs is becoming a serious global problem and, according to some forecasts, could soon reach the scale of the largest health threats facing societies today.
(rt/gs)
Source: naukawpolsce.pl