The potential of bacteriophages to tackle both conventional and antibiotic-resistant bacterial infections is becoming more widely recognised. As research and clinical interest in phage therapy grows, one important consideration is the use of the combinations of multiple phages (“phage cocktails”), which allow complex infections to be treated while also minimising the emergence of bacterial resistance.

Why one phage isn’t always enough

One of the defining features of phages is their high degree of specificity. Phages are much more precise than chemical antibiotics with each phage infecting its own dedicated bacterial species, strain or subtype. This is one of phage therapy’s key advantages, allowing harmful pathogens to be precisely targeted and eliminated without disrupting beneficial bacteria that make up a healthy a healthy microbiome. In contrast, broad-spectrum antibiotics act indiscriminately and can wipe out both harmful and helpful bacteria, increasing the risk of dysbiosis and other secondary infections.

However, real-world infections are not always caused by a single, uniform bacterial strain or species, particularly when it comes to complex, chronic or wound-related infections. Infections that affect populations can be diverse, even when caused by the same bacterial strain and in some polymicrobial infections (where multiple bacteria infect the same individual), multiple pathogenic species can be involved. Even when a single strain is the pathogen, there is often a mix of closely related strains, each with slightly different genetic differences and characteristics that can affect how bacteria respond to treatment.

While phages have the unique advantage of being able to be deployed as a personalised medicine, where a phage or combination of phages is put together to treat an infection in a single patient, the widespread adoption of phages requires a broad coverage of target strains, so a product can be used without prior knowledge of the infecting bacteria. In these cases, using a targeted combination of phages offers a viable approach, working together to tackle multiple strains simultaneously, enhancing coverage, therapeutic efficacy and speed of treatment.

Enter phage cocktails

“Phage cocktails” combine multiple, carefully selected phages into a single treatment, broadening the range of bacterial strains being targeted.

Rather than trying to find the perfect single phage match, cocktails allow for a more comprehensive approach to enable efficacy against a wide variety of bacterial strains and increase the chances of eliminating the desired target quickly and effectively.

This approach can help:

• Reduce the time needed to identify an effective treatment, speeding up the treatment process
• Improve the likelihood of success across diverse infections
• Lower the risk of bacterial resistance

This approach offers a practical solution for complex and variable infections, while personalised phage therapies remain valuable in more targeted cases.  In fact, to fully utilise the strengths of bacteriophages, the two approaches should be used in a complimentary fashion, with a frontline generic phage cocktail with broad coverage, supported by a second line of personalised therapies, where the initial treatment has failed.

Keeping phage cocktails up-to-date

To use phages to their full potential, phage cocktails should be periodically updated, so that they maintain their efficiency, for example, if new bacterial strains emerge or resistance patterns shift.

This ability to “swap in” or remove optimised phages means that treatments can stay relevant and effective without needing to completely redesign an approach from the ground up and in some cases without the need for new clinical trials.

Bringing any new treatment to patients requires rigorous testing. Clinical trials are a critical part of building trust and protecting patients – designed to ensure that medicines are safe, effective, and manufactured to the highest standards before they are widely used.  However, clinical trial regulations were designed with traditional chemical antibiotics in mind and are not always flexible enough to support the most effective development of non-traditional antibiotics, such as phages.

Under conventional pharmaceutical regulations, changes to the composition of a medicinal product can trigger the need for a full new clinical trial. For phage therapy, this risks slowing progress and limiting patient access at a time when alternative therapeutic treatments are desperately needed.

Understanding the phage regulatory framework

Our interactions with Medicines and Healthcare products Regulatory Agency (MHRA) in the UK suggest it is possible to update phage cocktails under existing regulations, but the specific mechanisms by which this could happen remain untested.  Broad clarity is being provided through recent phage-specific guidelines from the MHRA, as well as those from the EU in the veterinary health field but also through the new draft EU pharmaceutical regulations, the latter that specifically mentions phages and updating phage cocktails. In an ideal world, licensed phage cocktails will be supplemented by phages from a specified collection (i.e. a multi-strain dossier is taken through the regulatory pathway), but if needed, new phages could be isolated where required. These individual phages could be added or removed from an approved cocktail within a validated framework, without the need to re-run full clinical trials each time a change is made.

This type of flexibility has clear, real-world benefits. Infections don’t wait, and the ability to make targeted updates to a phage cocktail means treatments can keep pace with evolving bacterial populations without unnecessary delays. Rather than restarting lengthy development processes, refining an existing and clinically validated cocktail could help streamline timelines and support faster patient access where it’s needed most.

It would also introduce efficiencies in manufacturing, enabling processes to remain consistent while incorporating optimised components. Taken together, this would support a more responsive, practical model that is better aligned with the realities of treating evolving bacterial infections in an era of antimicrobial resistance.

Combined with, robust assays, appropriate quality control, rigorous oversight and Good Manufacturing Practice (GMP) standards, such an approach would accommodate the unique nature of phage therapy. It would reflect how bacteria and phages behave in the real world and enable the development of licensed phage therapies that could be updated, scaled and deployed.

A flexible approach for a changing landscape

Overall, phage cocktails represent more than just a combination therapy – they offer a flexible, future-facing approach to treating bacterial infections.

By enabling formulations to be refined and updated within existing frameworks, phage cocktails have the potential to keep pace with bacterial change in a way that is scientifically justified and essential for scalability. As the field continues to evolve, this adaptability could prove to be one of phage therapy’s greatest strengths.