Phage Therapy’s Future: Tackling Antimicrobial Resistance With Precision Viruses

Many bacteriophages, or phages, are floating and slowly moving within the organism.

(Adobe Stock 643597600 by Dabarti)

As the global health community confronts the growing threat of antimicrobial resistance (AMR), researchers are turning to one of nature’s oldest bacterial enemies—bacteriophages. In this exclusive Q&A, Infection Control Today^® (ICT^®) speaks with Ran Nir-Paz, MD, an infectious diseases specialist at Hadassah Medical Organization in Jerusalem and a Professor of Microbiology and Medicine at the Department of Clinical Microbiology and Infectious Diseases at the Hadassah Hebrew University Medical Center.

Nir-Paz, who is also the cofounder of the Israeli Phage Therapy Center, shares insight into the mechanisms, benefits, and regulatory hurdles surrounding phage therapy. From targeting pathogens like Pseudomonas aeruginosa to early success in diabetic foot ulcer treatment, phage therapy is gaining renewed attention as a targeted, potentially life-saving complement to traditional antibiotics. However, widespread adoption will require robust evidence and thoughtful implementation.

ICT: What exactly are bacteriophages, and how do they work to target and kill bacteria?
Ran Nir-Paz, MD: Bacteriophages, or phages, are viruses that infect only bacteria and do not affect other organisms. They do not necessarily kill bacteria; some cause chronic infections in bacteria, while others kill their host bacteria.

Ran Nir-Paz, MD.

(Image credit to Ran Nir-Paz, MD.)

ICT: Can you explain how bacteriophages specifically attack bacteria like Pseudomonas aeruginosa? What makes them different from traditional antibiotics?
R N-P: Unlike antibiotics, bacteriophages multiply within the bacteria they target. As a result, they replicate at the pathogen's location, which can create a long-lasting effect after treatment. Theoretically, this may reduce the need for additional dosages if the right dose of phages reaches the target site. However, this potential advantage still needs to be proven clinically, and the right methods to enhance this effect may need to be developed.

ICT: How are phages identified and selected for specific bacterial infections? Is it a matter of trial and error or a more systematic approach?

RN-P: Both approaches are used. We still do not have a precise method to predict the perfect phage activity against a specific bacterium. Typically, large amounts of fluids from sources like sewage or other samples are screened for phages that infect bacteria. Then, a series of tests are performed in the lab to check if the target bacteria are susceptible to the phage, and if the combination of phage and antibiotics works well together. Genetic coding of phages is also conducted to identify potentially harmful genes. While the process is systematic, it requires time and effort to find the right phage.

ICT: As antimicrobial resistance becomes a growing concern, how do phages offer a potential solution? How do they overcome some of the limitations of antibiotics?
RN-P: Phages could become a valuable tool for fighting infections. They will not replace antibiotics, but may be useful when antibiotics prove to be ineffective. However, at this stage, we lack a good model to predict how and when phages will work best.

ICT: Your recent study on phage therapy for diabetic foot ulcers showed positive results. Can you tell us about the study and how the phage cocktail performed compared to the placebo?
RN-P: The main result was that there was no harm. The study was not powered to provide definitive results on the efficacy of phages, and additional studies with larger numbers of patients are needed. However, it seems that some patients did experience benefits.

ICT: What challenges exist when applying phage therapy topically, as opposed to treating internal infections, and how did you address those challenges in your diabetic foot ulcer study?
RN-P: Topical administration is easier than administering phages intravenously or to an invasive infection site. The main difference lies in the type of safety measures and quality assurance processes needed, which tend to be more flexible for local applications.

ICT: Given that multiple bacterial infections often complicate diabetic foot ulcers, how can phages be tailored to address these complexities?
RN-P: That's a great question, but the answer is still unclear. Possibly, in such infections, only the major target bacteria need to be treated with local, well-known measures. Another approach that needs clinical validation is that a cocktail of phages could help address this complexity. But again, this is an area that needs further study.

ICT: While phage therapy shows great promise, what are some of the major hurdles to scaling this treatment for widespread use?
RN-P: One major hurdle is determining the appropriate approach—whether a personalized or self-administered product would be more effective. Another challenge is figuring out the right economic model to make such products viable. Finally, and probably most importantly, we need to provide evidence of the specific indications and protocols under which phages will become an effective treatment. There is still a long way to go.

ICT: Are there regulatory or safety concerns with using phages in clinical settings that must be overcome before they can be used more routinely?
RN-P: Phages are generally considered safe to use. However, since they are a new modality in modern medicine, much work is needed to establish proper regulatory pathways and safety protocols to ensure that more patients can be treated safely in the future.

ICT: What’s the biggest misconception about phages or phage therapy that you think needs to be addressed, especially when it comes to their potential in mainstream medicine?
RN-P: I'm not sure if there is a significant misconception. Modern medicine relies on evidence-based facts to support a treatment. Currently, large-scale evidence on phages is still lacking, and it may take years to obtain this.

ICT: Could you envision phage therapy becoming a standard treatment in hospitals, or do you think it will always be a niche approach for certain types of infections?
RN-P: It will likely be a combination of both. Currently, the need for specific expertise means that phage therapy requires highly specialized centers. Hopefully, as more indications and protocols become available, it will be used more widely, but with the current evidence, it will likely remain associated with higher-level facilities and not be available in every community center or hospital.

ICT: What do you see as the next steps in phage research? Are there new areas or infections you think phage therapy could significantly impact?
RN-P: The next step is to provide solid evidence for phage activity and superiority in specific indications—whether it's urinary tract infections, diabetic foot ulcers, bone and joint infections, or bloodstream infections. A strong clinical trial in any of these areas could create the most significant impact.

ICT: Do you think phage therapy could eventually be integrated into the current antibiotic regimen, or do you foresee it being a standalone treatment?
RN-P: It's hard to say, but it's likely that phage therapy will serve as an adjunct to antibiotics in cases where antibiotics alone have failed.

ICT: Finally, what would you say to someone skeptical about phage therapy, especially given its long and somewhat controversial history in medicine?
RN-P: Skepticism is always healthy! It's what drives science and clinical trials. The combination of enthusiasm and skepticism will likely provide us with the best evidence to determine the right indications and protocols for phages in treating persistent infections. In my view, phages will not replace conventional antibiotics, and this is not the current goal of any ongoing trials.