Phage therapy presents a promising solution in the fight against antimicrobial resistance, particularly for infections caused by multidrug-resistant bacteria. As the need for, and interest in, phage therapy grows, hospital pharmacists and clinicians must understand guidance on patient selection, treatment administration and regulatory compliance. Here, Gerry Hughes explores the current landscape of phage therapy, including the role of healthcare professionals and optimising patient outcomes, with insights into two established phage services.
The phages discussed in this article refer to naturally occurring phages and phage cocktails and do not refer to genetically modified phages.
Bacteriophages, or phages, are naturally occurring viruses that specifically target and kill bacteria. Discovered in the early 20th century, phages were initially used as an alternative to antibiotics for treating bacterial infections. However, the widespread use of antibiotics led to a decline in their use in Western medicine.
In recent years, phages have regained attention due to the growing problem of antimicrobial resistance (AMR). This issue arises when bacteria develop resistance to multiple antibiotics, rendering traditional treatments less effective, especially for infections caused by multidrug-resistant (MDR) organisms such as Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli.
Phage therapy has shown promise as a targeted, adaptive solution for these infections. As global demand for effective AMR treatments grows, phage therapy provides an alternative to combatting MDR infections.
Phage therapy is especially beneficial for treating infections caused by MDR bacteria when conventional antibiotics fail. A recent multicentre, retrospective study involving 100 patients treated with personalised phage therapy reported promising results. The study, conducted from 2008 to 2022, involved 35 hospitals across 12 countries and demonstrated clinical improvement in 77.2% of infections, with 61.3% of bacterial infections eradicated by the targeted bacteriophages.
The most commonly treated pathogens were Pseudomonas aeruginosa and Staphylococcus aureus, with phage preparations tailored to the specific bacterial strains isolated from each patient. When phage therapy was combined with antibiotics, bacterial eradication was more likely, highlighting the synergy between the two.
Accessing phage therapy
The process of guiding hospital pharmacists and clinicians on the safe and effective delivery of phage therapy is collaborative and involves multiple stages.
‘Once a request comes in, we get in touch with the treating doctor,’ explains Dr Maya Merabishvili, senior scientist at Queen Astrid Military Hospital (QAMH) in Belgium – a leading centre for phage therapy. ‘We then receive the medical file, assess whether the case is eligible for phage therapy, and if we have phages available for the pathogen.
‘The bacterial strain is sent to our lab, where we test our phage collection for compatibility. If no phages work, we inform the hospital that we have no solution. If several phages are effective, we test their compatibility to determine the best combination.’
The information on phage-antibiotic synergy is then provided to the clinicians involved in the patient’s care. ‘We prepare a phagogram detailing which phages showed activity,’ Dr Merabishvili continues. ‘We also check which antibiotics can be used with the phages and send the phages along with this information to the hospital pharmacy.’
In the UK, the National Clinical Phage Service, which was established in 2022, provides similar support. Dr Josh Jones, virologist and director of this service, explains that the service ‘operates a “bench to bedside” service for clinicians using phage therapy’, which begins with the clinician filling out a request form.
‘We’ll screen our phage library against the bacterial isolate we receive, and if we get a match, we’ll contact the manufacturer to get the phage produced, often within the EU, and then import it,’ he explains. ‘If we don’t get a match from our diagnostic panel, we go to international groups to source phages from there.’
Supporting healthcare professionals
Hospital pharmacists are essential brokers in sourcing safe, evidence-based phage therapy for patients with infections.
Phage therapy is particularly suitable for patients with chronic infections or those infected with MDR pathogens, and hospital pharmacists involved in antimicrobial stewardship or infectious disease management may assist in selecting appropriate candidates.
Once phage therapy is deemed suitable, hospital pharmacists with expertise in medicines management or aseptic compounding are typically involved in the safe procurement, storage, and administration of phages.
Dr Jones and a group of consultants from the UK have recently published guidance on assessing the suitability of patients for phage therapy, including considerations for special populations such as pregnant or breastfeeding patients, which can be used alongside support from the National Clinical Phage Service.
‘We offer clinical and scientific support to multidisciplinary teams and help with unlicensed medicines applications,’ Dr Jones says. ‘For pharmacists, we provide support in handling and storing phages safely. It’s about capacity building, education and awareness for NHS pharmacy departments so they can confidently handle phages in their own Trusts.’
Preparation and administration
Hospital pharmacists must ensure that phage preparations meet stringent safety standards and there are a range of quality assurance measures that should be taken into account, including dosing, stability and, as Dr Merabishvili explains, sterility.
‘The phages we send are sterile preparations, and we make sure the environment guarantees the sterility of the final product that will go to the patient. We work within biosafety cabinets to ensure the final product is sterile,’ she says.
In some cases, hospital pharmacists may need to perform further compounding of phage products and guidance on dilution of phages is also provided within Dr Merabishvili’s process.
‘Sometimes, the phage preparations we send are concentrated, and they need to be diluted by 100 or 1,000 times,’ she says. ‘This can be challenging for pharmacists [so] we provide a schema outlining the proper dilution steps.’
In contrast, phage therapy supplied by the UK’s National Clinical Phage Service comes in a ready-to-use format with no further manipulation required.
As phage therapy is still considered an unlicensed treatment, including in the EU and UK, hospital pharmacists must ensure that it is administered in compliance with regional regulations, and that informed consent is obtained from patients.
‘Phage therapy should be used in accordance with unlicensed medicines guidance, which pharmacists should be familiar with. Each local NHS Trust will also have its own unlicensed medicines policy,’ says Dr Jones.
Perceptions of phage therapy
How is phage therapy perceived by clinicians and patients? A recent survey of clinicians showed significant interest in phage therapy, especially given the rising threat of AMR. A majority of clinicians (71%) expressed willingness to consider phage therapy in appropriate cases, though just over half (59%) had previously heard of it.
Patient perceptions are similarly positive. In a study of diabetic foot infection patients, most were initially unfamiliar with phage therapy. However, when provided with clear information, over 89% said they would consider phage therapy if antibiotics failed. Patients viewed phage therapy as a hopeful alternative to invasive treatments like amputation.
Many patients also expressed interest in participating in clinical trials for phage therapy, indicating a strong desire for additional treatment options in the face of AMR.
The future of phage therapy and AMR
Phage therapy holds significant potential in the fight against AMR, offering a promising solution for difficult-to-treat infections. The establishment of the UK’s National Clinical Phage Service marked a major step forward, and this, along with the work being done elsewhere in Europe, suggests there is considerable hope for the future.
As phage therapy develops, its integration into healthcare systems could revolutionise the treatment of infections, providing a sustainable, antibiotic-sparing approach. This innovation is poised to become a critical tool in addressing the global AMR crisis.
