Antimicrobial resistance: securing the future

Professor Mark Gilchrist

Imperial College Healthcare NHS Trust became the first UK healthcare organisation to be accredited by the Global Antimicrobial Stewardship Accreditation Scheme (GAMSAS) in July 2023. The British Society for Antimicrobial Chemotherapy (BSAC) also made the Trust a Centre of Excellence to support its wider antimicrobial stewardship networks. Alongside two other organisations, Imperial College Healthcare is one of only three centres to be accredited in the world. 

"Being recognised as a global leader in antimicrobial stewardship is not only a huge honour, it’s a vital step in the UK’s contribution to the international fight against AMR,” said Professor Mark Gilchrist, a consultant pharmacist in infectious diseases and head of antimicrobial stewardship at the Trust. 

“To be one of just three Centres of Excellence internationally and the first in the UK is amazing and we’re so proud to be paving the way. Approximately 40 per cent of our inpatients are on antimicrobials at any one time and the threat of antimicrobial resistance at the Trust itself is bigger than it has ever been. As a large NHS Trust, we have a responsibility to take steps in addressing this. 

"The awards and accreditations we now hold are recognition of our continuing commitment to using antibiotics appropriately. Something we should all, as healthcare professionals, be prioritising."

Mark is also a Professor of Practice (Infectious Diseases) at Imperial College London, who partner with Imperial College Healthcare in the National Institute for Health and Care Research (NIHR) Imperial Biomedical Research Centre (BRC), which focuses on infection and AMR as one of its 14 key themes of work. 

“Research and partnership is key. Working with Imperial College London, they continue to support and provide us with innovative ways to use antimicrobials responsibly in clinical practice. Alongside our awareness, education and feedback approach, this helps to spread the message that we need to protect our antimicrobials and provide healthcare staff with solutions.” 

Professor Graham Cooke

Professor Graham Cooke co-leads the infection and AMR research theme at the NIHR Imperial BRC. He says research is about improving diagnosis of infectious diseases, discovering new treatments and better using the ones we already have.

“And it’s about both discovery and implementation. We need to find new ways of diagnosing infections and actually start using those in practice. But we also need a continual pipeline of new treatments for those diseases, as well as to better understand how to use the ones we’ve got.” 

New tests are more important than some might realise. Dr Ravi Mehta, a BRC-funded researcher at Imperial College London and infectious diseases doctor at Imperial College Healthcare, discovered a molecule that is produced in the body when a person has a virus.  

This creates potential to test those with infection symptoms at hospital and stop giving antibiotics to patients with viruses, who won't benefit. Doctors can not risk allowing dangerous bacterial infections to worsen and, with no way to be sure if it is a virus, antibiotics are given to prevent a serious condition, such as sepsis. If a patient turns out to have a virus, this contributes to making bacteria more resistant.  

But preventing infections in the first place is also something the scientists need to help with. 

“There’s a wide range of areas we need to look at. Preventing bacterial infection is another one of them. Maybe with vaccines, perhaps with antibodies, or it could even be with completely new materials,” says Professor Cooke  

Another research project is looking at how antibiotic doses can be tailored to individuals, so that they receive the exact amount of medicine needed to treat their personal disease. The Centre for Antimicrobial Optimisation at Imperial College London plays a key role, alongside the NIHR Imperial BRC. 

“Some patients currently receive too much medicine and some receive too little. Precision medicine is a thread that runs throughout our BRC research work and we are looking at ways to use antibiotics more precisely for individuals.”

“Ultimately, we have to better understand how to use the antimicrobial treatments we’ve got so we can protect them for the future. But we also need that pipeline of new treatments for all the new bugs that are going to be emerging that are resistant to the treatments we have.”

Tom Swaine

Around 4 million people in the UK (6 per cent of the population) have a penicillin allergy label on their medical record. But more than 90 per cent of are not actually allergic to penicillin when they are fully assessed.  

Specialty registrar in infectious diseases, Tom Swaine, wants people to better understand penicillin allergy. “Having a penicillin allergy label limits the choice of antibiotics we can use and leads to the use of antibiotics that are more expensive, less effective, have more side effects, and have the potential to worsen antimicrobial resistance. And we know AMR poses a global threat to human health and development.” 

“Many people are mislabelled because they report minor symptoms like abdominal pain, nausea, diarrhoea, headache or strange taste. These are not true signs of a penicillin allergy,” said Tom. 

“Many are also told they have a penicillin allergy because they had a rash after taking antibiotics in childhood – however, we know many of these rashes are caused by viral infections and are not signs of a true allergy. Penicillin allergies are also not lifelong. Up to 50 per cent will be lost after five years, and up to 80 per cent by ten years.” 

Aneeka Chavda is an infection pharmacist at Imperial College Healthcare and is part of a team working to set up a penicillin allergy de-labelling service that can safely and confidently remove potentially harmful false penicillin allergy labels for patients.

“Correctly identifying those who are not actually allergic to penicillins can improve antibiotic prescribing and combat the risk of antimicrobial resistance by allowing patients to access safer, less toxic medicines and sometimes more effective therapy. 

"We are focusing on how penicillin allergies are evaluated and how penicillin allergy labels can be safely removed. By targeting patients who are already in hospital, who can be readily evaluated, we can ensure they are on the best antibiotic therapy.” 

Tom is hopeful about expanding a de-labelling service across the sector in North West London but says that AMR is everyone’s business. “Everyone should check their medical record the next time they visit their GP to ensure that they are not wrongly labelled as allergic to penicillin. Together, we can fight antimicrobial resistance.”

Alexander Fleming’s chance discovery of penicillin in 1928 is perhaps one of the most famous serendipitous discoveries in medicine. But a little-known story from the dawn of antibiotics is how siblings, Leonard and Dora Colebrook, pioneered the use of Prontosil red, an antibacterial that became widely available years before penicillin could be used. The mass production of penicillin for clinical use actually took a decade after its discovery. 

Imperial's NIHR Imperial BRC Colebrook research laboratory at Charing Cross Hospital is a facility that provides state-of-the-art microbiology research space to support translational research in AMR. Its co-location with the Trust’s Diagnostic Laboratory supports clinically-relevant studies by both NHS and academic researchers.  

The lab opened at the start of the Covid-19 pandemic and is named in honour of Dora Colebrook and her brother Leonard, who both played significant roles in the history of antibacterial use and infection control.  

In 1929 Leonard Colebrook who was a researcher at Queen Charlotte's Hospital, now part of Imperial College Healthcare NHS Trust, focused his research interest on sepsis following childbirth, which killed around 2000 women in England and Wales at that time.

In 1936 Leonard showed for the first time in a clinical trial that Prontosil was effective against streptococcal infections and hence a cure for bacterial sepsis following childbirth.  Within a year, the use of Prontosil was widespread and pre-dated general use of penicillin by a decade. Resistance to this type of antibiotic proved problematic, as predicted by Colebrook.

His sister Dora Colebrook was a bacteriologist also working at Queen Charlotte’s. She undertook groundbreaking work to demonstrate that the streptococci that caused infections and deaths in women following childbirth were the very same streptococci present in the throats of those in the household or healthcare workers caring for the women. This confirmed that good hygiene practices and what we now know as PPE could reduce the incidence and transmission of puerperal sepsis and Streptococcus A in many settings. Dora’s 1935 MRC report has been published online.

Professor Shiranee Sriskandan leads a research group that uses the Colebrook Lab to support their research on Streptococcus pyogenes, the bacterium that causes tonsillitis.

"If we want to use antibiotics wisely, it is important to know what sort of infection a patient has as quickly as possible. Right now we wait for one to two days for traditional culture results. The new lab has provided a great opportunity for clinicians and scientists to access biobanked samples from cases of real infection, enabling new biomarkers of infection to be discovered. This could help us work out what’s wrong with a patient much more rapidly than at present," said Shiranee.

Professor the Lord Darzi of Denham

A future where we can control the spread of AMR and keep antibiotics working is still possible. But making this a reality needs an urgent and wide-ranging approach to research that means we can take scientific discovery and use it quickly to develop new and effective solutions.  

The problem is, innovative research will be futile unless accompanied by collective behaviour change from the public, healthcare professionals and policy makers.  

The Fleming Initiative is an innovative and collaborative new approach led by Imperial College Healthcare NHS Trust and Imperial College London to tackle AMR around the world by putting society at the heart of solving the AMR crisis. At the heart of the initiative is the Fleming Centre, which will be based at St Mary's Hospital, where Fleming's laboratory still exists today. The centre, which also forms an important part of the Paddington Life Sciences Development, will work closely with networks around the world to catalyse worldwide action.

An appeal to fund the initiative was launched in 2023 with HRH Prince William as Patron and global biopharma company, GSK, has pledged £45m to the initiative as its first founding partner.

Professor the Lord Darzi of Denham chairs the Fleming Initiative, with the Fleming Centre due to open in 2028 and mark a century since Alexander Fleming’s historic discovery. “The Fleming Initiative aims to build on this legacy and raise awareness, meaningfully involve diverse public voices, drive behaviour change, and catalyse action to address AMR on a global scale.