The research team led by Bartłomiej Grygorcewicz, PhD, is investigating their potential in hospital-acquired infections and in biofilms that are resistant to conventional therapy.

The work comes amid increasing global concern about antibiotic resistance. Health authorities report a rising number of infections caused by so-called superbugs, which are resistant to most or all known antibiotics.

According to international data, the spread of these pathogens is accelerating and is considered a growing public-health threat.

Scientists continue to search for new strategies to combat these organisms, but progress in antibiotic development has been slow. The WHO has noted that the development of new drugs in this category has “practically stalled,” with only two or three entirely new classes launched in recent decades and with most new products representing modifications of existing compounds. This has contributed to increased interest in alternative methods, including phage therapy.

“Choosing an effective phage takes days or weeks, not decades, as with new antibiotics,” Grygorcewicz told the Polish Press Agency (PAP). “Furthermore, phages can be flexibly combined into cocktails, allowing therapy to be effective even when a bacterium has become resistant to one virus.” He added that infections involving multidrug-resistant bacteria remain one of the foremost challenges in modern medicine.

According to Grygorcewicz, biofilm-associated infections are particularly difficult to treat. Biofilms are multilayered structures consisting of microorganisms embedded in a matrix that limits the penetration of drugs and immune cells.

They commonly form on catheters, implants, surgical wounds and in the respiratory tract. “Biofilm structures are exceptionally difficult to destroy. Even if an antibiotic penetrates them, some of the cells in the biofilm become dormant and remain insensitive to treatment. Therefore, these infections can persist for months, or recur,” he said.

The team’s latest findings, published in Microbes and Infection, focus on infections caused by Staphylococcus aureus and Candida albicans, two organisms that can create complex mixed biofilms in certain clinical contexts. Grygorcewicz said that while phages effectively target bacteria, they do not eliminate the full mixed biofilm. “Bacteriophages alone are effective against bacteria, but they do not eliminate the entire mixed biofilm, in which bacteria and fungi coexist. The best results are achieved by combining phages with antibiotics and antifungal drugs. A properly selected combination is much more effective than either agent alone,” he said.

During the study, scientists tested how various combinations of phages, antibiotics and antifungal agents affected the ability to control the biofilm. They found that the composition of the therapy was not the only critical factor; the order in which the components were administered also played a significant role. In some test conditions, differences in effectiveness were substantial.

In a fluid-phase model intended to reflect infections developing in blood or lymph, the most effective sequence began with bacteriophages, followed by an antifungal agent and then an antibiotic. This sequence reduced both the bacterial and fungal components of the infection. In established biofilms, which are more resistant to treatment, the most effective approach was to administer all three agents simultaneously or to apply phages with an antibiotic before adding the antifungal drug.

Grygorcewicz said the role of phages in combination therapy is often misinterpreted. Phages do not carry or deliver drugs; instead they weaken bacterial cells, making them more vulnerable to antibiotics and antifungals. In some cases, phages disrupt bacterial structures, aiding drug penetration. In other cases, antibiotics promote phage replication, increasing their activity. He said this makes sequencing important. “We observed that when the bacteriophage is administered first, it loosens the biofilm structure. This allows new drugs to more easily penetrate the body and reach hidden microorganisms,” he said.

According to the researchers, the findings could support the development of more effective strategies for treating infections that do not respond to available medications. Phage therapy is already being tested in Georgia, Belgium, Australia and the United States, and is increasingly considered a potential alternative to antibiotics. In Poland, experimental phage treatments are conducted at the Hirszfeld Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences in Wrocław.

Despite this progress, Grygorcewicz said the path to widespread clinical use remains long. “The biggest challenge currently lies in legal regulations. The European Union does not yet have clear regulations specifying what phage preparations should look like, or in which cases they can be used in humans,” he said.

He added that the first veterinary recommendations were issued only recently. Countries such as Belgium have implemented the magistral phage model, which permits the individual selection and preparation of phage formulations for specific patients. Under this system, phages are treated as magistral medicines prepared by a pharmacist based on a doctor’s prescription. The infecting bacterial strain is isolated from the patient, appropriate phages are selected in the laboratory and combined into a phage cocktail, and the preparation is then delivered to the hospital for personalised therapy.

A second challenge arises from the narrow specificity of phages. “Each of them attacks only a specific strain of bacteria, which means the therapy must always be tailored to the specific needs. This is both an advantage and a disadvantage of phages. Thanks to their precision, they do not destroy beneficial microflora, but they do require precise matching to a specific pathogen,” Grygorcewicz said.

He is a co-founder of the Polish Society for Research on Viruses of Microorganisms, which brings together specialists working in the field. “We strive to unite this community at joint conferences, build collaboration between centres, exchange experiences, and support the development of bacteriophage research in our Poland,” he said.

He added that interest in the subject continues to grow. “This topic is of enormous interest worldwide. Although the development of phage therapy research is outpacing current regulations, we hope that in the coming years the law will begin to catch up with scientific progress. The problem of increasing resistance to antimicrobial drugs is becoming increasingly serious and, according to forecasts, may soon rival the scale of today’s greatest health threats,” he said.

Katarzyna Czechowicz (PAP)

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