Bacteriophages, or phages, are viruses that selectively infect bacteria, replicate within them, and ultimately kill bacterial cells. They are being studied as a complement or alternative to antibiotics, particularly as antimicrobial resistance limits conventional treatment options.

This approach may benefit patients in whom conventional antibiotic therapy is no longer effective. Potential applications include the following:

• Chronic respiratory infections 
• Severe systemic infections 
• Infections of the bones, joints, skin, or ENT tract 

Phage therapy is already being used in countries such as Belgium and the US, although in Western Europe, it is still primarily provided outside standard care. Current approaches include individualized treatment, special national programs, preparation for hospital pharmacies, and clinical trials. However, Europe does not yet have a harmonized legal and regulatory framework that would allow phage therapies to be widely offered in routine clinical practice.

Personalized Phage Therapy

An international working group led by the German Society for Infectious Diseases developed guidelines for personalized phage therapy. The group included 20 professional societies, patient advocacy groups, regulatory authorities, and 18 international experts. 

The guideline contains more than 60 recommendations covering phage selection and testing, infrastructure, preparation and quality control, administration, monitoring, documentation, and future research. A registry was also established as part of the guideline development. This consensus statement has been published in Nature Medicine. 

"Because phages act very specifically against their bacterial hosts, an appropriate phage must be identified for each treatment and tested against the bacterial strain causing the current infection," said Silvia Würstle, MD, MBA, a research fellow from the Department of Internal Medicine II, Infectious Diseases, University Medicine Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany, and lead author of the guideline, during a press briefing with the Science Media Center.

"An interdisciplinary approach is also important," stated Annika Y. Classen , MD, a specialist in internal medicine and infectious diseases, Department I of Internal Medicine, Division of Infectious Diseases, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany, and an author of the guideline.

Interdisciplinary Assessment

The guideline therefore proposes that each case be assessed by an interdisciplinary approach comprising the treating physicians, clinical microbiologists, and recognized phage experts. Before treatment begins, the selected phage should be tested as soon as possible against the current bacterial strain — the so-called "phage match." This is important because bacterial susceptibility to phages can change over time. In polymicrobial infections, all causative bacterial species should undergo phage susceptibility testing. 

Würstle noted that personalized phage therapy may be considered when established treatment options are ineffective, unavailable, or unsuitable. To date, clinical research has indicated a favorable safety profile when phages are manufactured and administered in accordance with appropriate quality standards. However, their efficacy has not yet been sufficiently demonstrated in controlled clinical trials. Therefore, the new guideline considers phage therapy as an individualized treatment option that must be evaluated on a case-by-case basis, rather than the generally ​available standard treatment. 

A Century of Phages

Phages have been in use for over 100 years. In 1919, a 12-year-old boy with severe dysentery was treated with phages. In 1939, Behringwerke introduced Dysentery-Polyfagin for shigella infections, and in 1962, Intestolysin was used in East Germany against typhoid fever, paratyphoid, dysentery, and pathogenic Escherichia coli infections.

According to Classen, renewed interest in phages reflects the increasing challenge of infections caused by antibiotic-resistant bacteria in clinical practice.

"We need to supplement our antibiotic strategies. However, new antibiotics are not currently coming into the market in the quantities we need to address these resistance issues," Classen said.

A potential advantage is that antibiotic-resistant bacteria may remain susceptible to phages because the underlying resistance mechanisms can differ.

Phages are highly specific and target specific bacterial species. "This enables decolonization approaches that are gentler on the bacterial flora than conventional antibiotics, which are less selective," Classen said. Another potential advantage of phages is their wide availability.

Early Clinical Experience

Würstle successfully treated 10 patients with phages in Frankfurt. "All patients have benefited from this treatment, which has made me incredibly happy. We are currently able to treat Pseudomonas aeruginosa and Staphylococcus aureus, with more to follow," she reported.

Phages are available in formulations for intravenous administration, inhalation, nasal administration, and as a sterile hydrogel for wounds.

However, Würstle stressed that "phages are not a miracle cure." Observational data provide early indications of potential treatment benefits. In a Belgian case series of 100 treated patients, the clinical status improved in 77%, while the target bacteria were no longer detectable in 61% of cases, she reported. However, such findings cannot replace the evidence from controlled clinical trials.

Close monitoring is important because rapid bacterial breakdown caused by phages can trigger fever. In such cases, the phage dose may need to be reduced. Treatment may also be administered at too low a dose because phage concentrations can decline during months of storage. Concentration, therefore, needs to be checked before treatment begins.

Evidence Still Limited

Jan Rupp , MD, a professor and head of the Department of Infectious Diseases and Microbiology at Lübeck University and the University Medical Center Schleswig-Holstein, Lübeck, Germany, who was not involved in developing the guidelines, emphasized the need for new treatment options for multidrug-resistant pathogens. He suggested that combining antibiotics with phages could provide additional therapeutic options.

Classen confirmed that these guidelines do not yet provide direct treatment recommendations. "There are very few studies that demonstrate the effectiveness of phages. We therefore cannot say, 'Use these specific phages when a patient has pneumonia,' because that data does not exist."

As soon as more evidence from clinical trials becomes available, more specific treatment recommendations will be followed. Würstle and Classen also emphasized the importance of documenting every case in the registry to generate evidence.

On the basis of the number of hospitalized patients with multidrug-resistant pathogens, Rupp estimated that approximately 10,000 patients in Germany could be eligible for phage therapy. Classen has identified a range of potential applications. For example, phages can be administered directly into the bladder to treat urinary tract infections or injected into a joint to treat joint infections.

A potential preventive approach would be to apply phages directly to prostheses before implantation. Rupp hopes that phage therapy will emerge from its "niche status and play a clear role, for example, as an adjunct therapy to antibiotic treatment for severe multidrug-resistant pathogens. I believe that's where the greatest need lies," he concluded.

This story was translated from Medscape's German edition.