Learning every day in the battle against superbugs

Treating infections is becoming increasingly difficult due to antimicrobial resistance (AMR).

With AMR, bacteria, viruses and fungi change to become ‘resistant’ to medicines used against them.

This means medicines like antibiotics are no longer effective against them. This can make infections more difficult to treat. It also increases the risk of serious illness and death.

Consultant Microbiologist Professor Kordo Saeed is using research to help tackle this major global health challenge.

Professor Saeed is based at University Hospital Southampton (UHS). His is also an Honorary Professor at the University of Southampton (UoS) and part of the NIHR Biomedical Research Centre: Southampton.

‘A serious issue for global health’

“The bugs are cleverer than us,” says Professor Saeed. “Sometimes you can see the evolution of a bug in front of your eyes. It might be sensitive to an antimicrobial today, but after exposure you come back the next day and see that it has developed resistance.”

Around 1.2 million people die each year from infections directly caused by AMR. When deaths associated with AMR are also included, the figure rises to around five million.

“Some people call AMR a slow pandemic, but that upsets me because it isn’t slow and it’s already here,” says Professor Saeed. “It is a serious issue for global health.”

The impact of AMR is not felt equally. Communities without strong healthcare and public health infrastructure, sanitation or access to education can face a much greater burden.

Political instability and conflict can compound those challenges. It can also increase the risk of infections, including those associated with AMR.

“Deaths related to AMR often affect populations who are less fortunate than us,” Professor Saeed explains. “These are things we can sometimes take for granted in the UK, but published data show higher mortality rates in places with less developed healthcare and public health infrastructure, including parts of sub-Saharan Africa.”

For Professor Saeed, tackling AMR therefore requires more than developing new medicines. Preventing infection through vaccination, sanitation and good hygiene is crucial.

So too is protecting the antimicrobials we already have. This can be done by helping healthcare professionals make better-informed treatment decisions.

Faster answers for clinicians and patients

A major focus of Professor Saeed’s work is improving diagnostic testing. This allows clinicians to identify infections faster and more accurately.

“My main work relating to antimicrobial resistance is about providing better diagnostics,” he says. “By better, I mean more accurate, but also much faster.”

Faster results can help clinicians select the most appropriate antimicrobial. Just as importantly, they can provide reassurance when a patient does not need antibiotics.

This is particularly important in intensive care. Antimicrobial use is high and treatment decisions often need to be made urgently.

“You need teamwork around diagnostics,” says Professor Saeed. “That includes rapid diagnostics, biomarkers and all the other investigations available to us. We use that information to treat infection, while also making sure we use antimicrobials carefully.”

Professor Saeed and his colleagues are developing rapid point-of-care tests. They are working with engineers at UoS’ Optoelectronics Research Centre and critical care teams at UHS.

The aim is to examine several biomarkers from a single blood sample. This could help doctors identify infections, and determine whether they are caused by bacteria or a virus. It could also help them recognise when a patient’s condition is deteriorating.

The team is also exploring rapid, cost-effective ways to measure antimicrobial levels in patients’ blood. This could help doctors give the right amount of a drug when treating complex infections.

Professor Saeed hopes these approaches could have an important impact on AMR and patient care, particularly in resource-limited settings.

UHS patients transferred from hospitals abroad can also be screened for resistant microorganisms. This helps to reduce the risk of them spreading within the hospital.

“If you prevent infection, you are less likely to need antibiotics,” Professor Saeed explains. “Surveillance helps us understand which bugs are circulating and how we should deal with them.”

Casting a wider diagnostic net

Over the past two years, Professor Saeed’s team has been exploring metagenomics. This could help diagnose respiratory infections in critically ill patients.

Metagenomics examines genetic material in a clinical sample to identify microorganisms. Since it does not have a particular target, Professor Saeed compares it to fishing with a net rather than a line.

The results can indicate which microorganisms are present, and in what quantities. Microbiologists interpret these, alongside the patient’s symptoms, medical history and other test results. The clinical team then decide what the results mean for treatment.

“As microbiologists, we interpret the information in the clinical context,” says Professor Saeed. “Decisions about treatment are then made by the multidisciplinary team.”

Professor Saeed is supporting the NHS Respiratory Metagenomics Network. Led by Guy’s and St Thomas’ NHS Foundation Trust, Southampton is one of seven early adopter sites. Colleagues from UoS, UHS and the NIHR BRC: Southampton are involved locally.

In Southampton, the technology is being explored in the laboratory. The team also aim to see how it could be used to improve patient care.

“You can have very good research that shows something is positive, but translating that into practice can be a real challenge,” says Professor Saeed. “Finding out what works for colleagues in real life is an area that really fascinates me.”

Improving diagnosis for sepsis and joint infections

Professor Saeed and his colleagues are also investigating other uses for metagenomics. They aim to see if it could provide faster answers when an infection is suspected in a patient’s bloodstream.

When a patient shows signs of sepsis, clinicians will often send blood cultures to the microbiology laboratory. These may help identify an organism within a day or two. Yet sometimes they remain incubated for five days without producing a result.

“A day or two is a long time for a patient with potential sepsis,” says Professor Saeed.

The team is researching whether metagenomic testing could provide useful answers faster.

Initial findings are promising, although the research is currently at an early stage. The next challenge will be to understand the technology’s wider impact.

This includes whether it changes antimicrobial use and helps tackle resistance. It also includes whether it improves patient outcomes and provides value across the health system.

Professor Saeed is also exploring ways to support the diagnosis of infection in artificial joints. This would use information about microorganisms and the patient’s response to them. He is working with colleagues at UoS and the University of Portsmouth on this.

When someone with a knee or hip replacement develops chronic pain, it can be difficult to determine the cause. It could either be a mechanical problem or an infection.

Conventional cultures from joint fluid may take between 10 and 14 days to give results. Metagenomics could potentially provide answers sooner.

The research asks two important questions. Firstly, is a microorganism present? And secondly, is the patient’s body responding to it in a way that suggests it is causing harm?

“We are trying to individualise the diagnosis for the particular patient, rather than relying on the technology alone,” explains Professor Saeed. “From there, we can give individualised treatment, whether that is surgery, antibiotics or both.”

Supporting better prescribing decisions

Hospitals across the UK use apps, such as MicroGuide, to access prescribing guidance for common infections.

Professor Saeed has been involved in research exploring how decision-support tools could be incorporated into these apps. This could help doctors choose the best antimicrobial treatment.

These tools could prompt clinicians to consider relevant factors. These include previous MRSA colonisation, diabetes, recent admission to intensive care, or recent hospital treatment abroad.

“The idea is not just to give clinicians a guideline to follow,” Professor Saeed explains. “It is to provide friendly decision support that prompts them to ask the relevant questions.”

MicroGuide I and II studies have given promising results. Researchers at UoS worked on them with the University of Portsmouth, University of Wales, NHS England and industry collaborators.

“I think this could help current and future NHS workers make better decisions around antimicrobial use,” says Professor Saeed.

Taking antimicrobial education global

Alongside his work in Southampton, Professor Saeed contributes to international action on AMR.

He chairs the Rapid Diagnostics and Biomarker Working Group of the International Society of Antimicrobial Chemotherapy. Through this, he has helped deliver educational workshops in Kasese, Uganda. These were aimed at doctors, nurses, pharmacists and community health teams. They raised awareness of antimicrobial use, resistance and infection prevention.

The most recent workshop expanded its reach to include community members, farmers and teachers. This reflects the need for AMR education to extend beyond hospitals and other healthcare settings.

“We want to promote good education about antimicrobials, antibiotics and infection in primary and secondary schools,” says Professor Saeed. “There is evidence that if you reach people early, you can have a much greater impact later.”

Students can also take what they have learnt back to their families and communities. This allows them to become ambassadors for infection prevention, sanitation, hygiene and the responsible use of antibiotics.

Professor Saeed is also working with Winchester Rotary to introduce AMR into wider global health education. This is building on the organisation’s support for vaccination and malaria prevention programmes.

Connecting the laboratory with real life

Tackling AMR requires collaboration, and microbiology provides a vital link between the laboratory and the patient’s bedside.

Microbiology can help healthcare teams understand how microorganisms are changing and identify infections. It can also help them turn scientific discoveries into better-informed treatment decisions.

“AMR is presenting us with more challenges, so we need to think about other solutions,” says Professor Saeed. “It is about understanding what works in research, but also what works in real life.”

That combination of continuous discovery and practical impact is what makes the field so compelling to him.

“Microbes and antimicrobials are always changing,” he adds. “Every day is a learning experience.”