Diabetic foot infections (DFIs) are a serious and often overlooked complication of diabetes, affecting up to a third of all diabetic patients globally. These infections can lead to devastating consequences, such as amputation or even death.
As the threat of antimicrobial resistance (AMR) continues to limit traditional treatment options, phage therapy offers a promising solution. By targeting antibiotic-resistant bacteria and biofilms that form in chronic wounds of the DFI, bacteriophages have been shown to improve outcomes in “compassionate use” cases – offering a viable alternative treatment option to reduce the global burden of these life-altering infections.
Diabetes cases on the rise
The International Diabetes Federation’s projections show that by 2045, approximately 783 million adults will be living with diabetes. Cases have surged dramatically since the 1980s, from 108 million to 536.6 million in 2021. This rise has resulted in millions of deaths, with nearly 50% of fatalities occurring in people under the age of 70.
More than 90% of these individuals have type 2 diabetes, a condition driven by factors such as urbanisation, an ageing population, decreasing levels of physical activity, and the growing prevalence of obesity.
Due to the body’s inability to produce or use insulin, and therefore regulate blood glucose, the long-term impact can result in major health issues, including blindness, kidney failure, cardiovascular disease and lower limb amputation. In the worst-case scenario, it can lead to death.
DFIs: a major health challenge
The impact of DFIs is staggering, with 19% to 34% of diabetic individuals expected to develop one during their lifetime. The infection often stems from poor circulation and reduced immune responses in the periphery, typically beginning as diabetic foot ulcers (DFUs). Once an ulcer forms, it creates an entry point for opportunistic bacteria, leading to a full-blown DFI.
The prognosis following a DFI diagnosis is bleak, with five and 10-year survival rates at roughly 50% and 25%, respectively – worse than some common cancers. Treatment can be incredibly challenging and expensive, placing a strain on healthcare systems worldwide. In the UK, the NHS spends up to £962 million each year on DFI-related care, while in the US, direct costs for diabetic foot disease was $80 billion in 2017.
The challenge of AMR
The rising rates of AMR are exacerbating the already significant challenges in treating DFIs. AMR occurs when bacteria evolve to fight against traditional treatments, including antibiotics, and is recognised as a leading global health threat. The World Health Organization (WHO) projects that AMR could lead to 10 million deaths annually by 2050, with the World Bank estimating healthcare costs could reach $1 trillion.
Due to their chronic nature, DFIs also make patients particularly vulnerable to infections from antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). As the global spread of these pathogens continues, the risk of treatment failure grows, highlighting the urgent need for innovative and alternative therapies to combat this escalating crisis.
Embracing phage therapy in DFI treatment
One potential solution lies in the use of bacteriophages, or phages. These microscopic viruses are naturally occurring predators of bacteria that infect, replicate within, and kill bacterial cells. While no phage products are currently licensed as human medicines, several “compassionate use” cases have demonstrated phage therapy’s effectiveness in treating DFIs.
In one study, conducted in Scotland with 10 patients, phage therapy prevented amputation in six cases, showed clear improvement in two and only failed in one. These results are particularly significant given that these patients had the most difficult to treat, severe infections where all other treatments had failed, and the only alternative was amputation.
Moreover, a healthcare economic analysis, conducted by Health Improvement Scotland found that combining phage therapy with the normal standard of care was both less costly and more effective than standard care alone. The findings highlight how phage therapy can improve patient outcomes while reducing healthcare costs associated with DFIs.
Where next?
UK biotech company NexaBiome is leading efforts to expand the use of phage therapy for DFIs. Through its patented phage stabilisation technology, the company is in the process of developing phage-treated wound dressings that are stable at room temperature, allowing for broader application both in hospitals and for outpatient care. Unlike the current compassionate use approach, NexaBiome is working to take phage therapy through clinical trials to develop licensed medicines that can be used more widely, on a global scale.
The UK government has recently highlighted the importance of phage therapy as part of its five-year national action plan to combat drug-resistant infections. With increased investment in infrastructure, manufacturing and clinical trials, it could become a cornerstone in the treatment of DFIs and other resistant infections.
