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Kent, Surrey and Sussex tackling antimicrobial resistance through research

Antimicrobial resistance, or AMR, is recognised as a serious global threat to human health. The UK government aims to contain and control antimicrobial resistance by 2040 and health research plays a vital role in finding solutions. The reduction of AMR is a priority for the National Institute for Health Research (NIHR) with NIHR funded AMR related research taking place across the whole of Kent, Surrey and Sussex.

Professor Martin Llewelyn is the AMR lead for the NIHR. He is also Professor in Infectious Diseases at Brighton and Sussex Medical School and a Consultant in Infectious Diseases at Brighton and Sussex University Hospitals NHS Trust.

Professor Llewelyn said: “AMR is sometimes referred to as a huge threat to modern medicine. Many of the advances of modern medicine for instance cancer chemotherapy and organ transplantation are only possible due to effective antimicrobials.

“The answer to AMR cannot just be developing new drugs. One of the things we have learnt over the last 70 years is that once a new antibiotic is introduced, AMR resistance follows soon after, so the research response needs to be broad. The response involves better diagnostic support tools to help doctors prescribe antibiotics accurately; ways to prevent infection through developing vaccines and better antibiotic stewardship.

“The NIHR is actively supporting AMR studies and we are looking to increase investigator-led and industry funded studies on the infection portfolio.”

Better “review and revise” - the Antibiotic Review Kit Hospitals (ARK-Hospital) Research Programme

Antibiotics fight infections caused by bacteria, but not all infections are caused by bacteria. Often it’s too early to be sure of what is causing an illness when a patient first comes to hospital and doctors may give antibiotics “just in case”.

In a bid to encourage a more prudent use of antibiotics in hospitals the Department of Health and Social Care guidance promotes a ‘Start Smart then Focus’ approach. This recommends the administration of early effective antibiotics with “review and revise” follow-up 24-72 hours later when a decision will be made to either stop or continue the antibiotics. However, for many reasons, “review and revise” is not very effective at controlling unnecessary antibiotic use. Figures indicate that when antibiotic prescriptions are reviewed by doctors the trend is to continue with the course.

This highlights the need of a mind-set change for doctors to move from a “continue or justify stop” to a “stop or justify continue” approach. And this is what the Antibiotic Review Kit- Hospitals (ARK-Hospital) Programme is working on. It’s an NIHR applied research programme which aims to reduce antibiotic overuse substantially and safely through better “review and revise” of antibiotic prescribing decisions at 48-72 hours.

The ARK-Hospital Programme introduces a package of measures which includes internet-based training, a prescription-based decision aid tool, regular supportive audit and feedback from pharmacists/infection specialists and an information leaflet for patients .

Professor Llewelyn leads the ARK-Hospital Programme clinical trial and the kit was first introduced at Royal Sussex County Hospital, Brighton in April 2017, where a feasibility study was conducted to test how it can be used in practice and what effect it has on prescribing behaviour. It’s also been trialed at Frimley Health Foundation Trust and at Surrey and Sussex Healthcare NHS Trust (SASH) as part of a network of sites which now includes over 40 hospitals from all four nations of the United Kingdom.

At SASH the ARK-Hospital Programme core team introduced a new adult drug chart across the trust (except in paediatrics and neonatal) to aid decision-making at the time of “review and revise”. The chart contains an updated ARK-Hospital Programme antibiotic prescription section to guide the prescriber and to help the reviewer at the stage of “review and revise”.

Although the new adult drug chart is in use across the trust, only selected wards took part during the study period – respiratory, care of the elderly and acute medicine.

The ARK decision aid on the adult drug chart helps the prescriber categorise the initial antibiotic prescription by diagnostic confidence:

  • Probable diagnosis of infection: Infection is the most likely diagnosis but diagnosis and treatment still needs to be reviewed, or
  • Possible risk from infection: Infection is not the most likely diagnosis but you want to use antibiotics as a precaution. In both cases prescriptions are time limited (to 48-72 hours)

At “review and revise” antibiotics will either be “stopped” or “continuation justified”.

During the trial a weekly audit was carried out by ARK core team members for the first month then fortnightly and monthly until week 12. Timely audit results were fed back by the consultant microbiologist, lead acute physician, respiratory registrar and physician associate to the trial ward areas every Wednesday and Friday.

Amy Lee is a lead antimicrobial pharmacist and part of the ARK-Hospital Programme core team. She said: “For the post implementation phase of ARK, pharmacists now take over the audit which has been incorporated into the monthly Good Antibiotic Prescribing Audit. I feedback the results at divisional level via email on a monthly basis. There is continuous effort of on-going education and training across the Trust. ARK is included in all staff induction in microbiology and infection control MAST training and information about ARK is available on our trust micro guide.”

The ARK-Programme also ran at Wexham Park Hospital, part of Frimley Health NHS Foundation Trust. The hospital took part in the pilot phase in summer 2017 and implemented the ARK-Hospitals Programme trial in full in November 2017. During the pilot phase 150 members of staff accessed the online tool part of the ARK Antibiotic Review Kit.

Dr Veronica Garcia-Arias, Consultant Microbiologist based at Wexham Park is the Principal Investigator for Frimley Health Foundation Trust. Dr Garcia-Arias said: “Tackling AMR requires behaviour change and we need to keep reminding doctors, nurses and other prescribers to use the ARK Antibiotic Review Kit toolkit so they do not revert to former habits. AMR stewardship needs commitment from everyone.

“Research is needed to standardise prescribing practice across the country, which will lead to prescribers gaining the confidence to stop giving patients unnecessary antibiotics.”

Antibiotics used for chest infections - the CAP-IT study

Respiratory tract infections are the commonest reason that children are prescribed antibiotics worldwide with amoxicillin being the recommended first line choice in the UK for pneumonia. Although amoxicillin is widely used there is debate surrounding the best dose and best duration of course to balance clinical efficacy with preventing the development of AMR. Research is helping to resolve this.

The Royal Alexandra Children’s Hospital in Brighton is taking part in the CAP-IT study- an NIHR Health Technology Assessment Programme funded study that examines the use of amoxicillin in pneumonia.

CAP-IT’s full title is “Efficacy, safety and impact on antimicrobial resistance of duration and dose of amoxicillin treatment for young children with Community-Acquired Pneumonia.”This blinded randomised controlled trial investigates whether giving children a lower dosage of amoxicillin for a shorter duration is just as good at treating pneumonia as using a higher dose for a longer duration.

Dr Emily Walton is a consultant paediatrician in emergency medicine within the Children’s Emergency Department at the Royal Alexandra Children’s Hospital. Emily is Principal Investigator for the CAP-IT study in Brighton.

Dr Walton said: “In this trial children are randomised to take antibiotics for either three or seven days, and to either take a lower or higher dose. We observe how quickly they recover and whether they need any more antibiotics after the original treatment. We also look at any side effects for the children and the impact of the different antibiotic courses on these. In addition swabs are taken for the Streptococcus Pneumoniae bacteria and we investigate the degree of AMR in the bacteria.

“We are already seeing antibiotic resistant bacteria and the situation will only get worse unless we can change prescribing behaviour- to do this we need good quality evidence. We chose to take part in this study in our Emergency Department as chest infections are such a common reason that children are brought to see us and therefore this is a key area where we could make a contribution to AMR research and where changes in practice could have a high impact on the health of children in the future in tackling the global AMR crisis.

“For this study to be successful and to encourage behaviour change when prescribing antibiotics it is important to have everyone who works in the ED engaged”.
Junior doctors and nurses were GCP trained to be able to work on the study.

Use of antibiotic in the neonatal environment - the GBS2 study

Another NIHR study tackles AMR within the neonatal environment. As part of the birth process, all babies go from a sterile environment inside the uterus, protected by mother’s immune system, to the outside world where they encounter many bacteria. Many of these are normal bacteria that inhabit the skin, mouth, throat and intestines and help to avert serious infections. But, sometimes, one of these bacteria can cause a serious infection in a new-born baby. These bacteria can include B Streptococcus (GBS). Approximately 25% of women have these bacteria in the vagina or lower bowel, and do not usually cause any health problems for the mother. Mostly there are no ill effects for the baby, however, 1-2% of newborns exposed to GBS develop a serious infection unless given antibiotics.

Some women are screened for GBS during their pregnancy but even if the screen is negative, GBS can appear later and the baby may need antibiotic treatment if other risk factors are identified at the point of birth, or if there are signs of infection.

Antibiotics given to the mother from the start of labour reduces the risk of the new-born baby developing early onset GBS disease, both by reduction of the chance of transmission and by giving the baby protective antibiotics before birth, providing they are given for long enough before delivery.

Yet, the majority of these babies do not have a GBS infection and are unnecessarily exposed to antibiotics and their side effects. The aim of the GBS2 study (full title - Accuracy of a rapid intrapartum test for maternal group B streptococcal colonisation and its potential to reduce antibiotic usage in mothers with risk factors) is to establish whether rapid testing technology which determines whether the mother is carrying GBS can be used in the labour ward to direct the appropriate and timely administration of preventative antibiotics. This is instead of giving antibiotics to all those with risk factors and whether this results in a reduction in antibiotic usage.

The GBS2 study took place at Maidstone and Tunbridge Wells NHS Trust (MTW), Royal Surrey County Hospital NHS Foundation Trust, Western Sussex Hospitals NHS Foundation Trust and Frimley Health Foundation NHS Trust.

Louise Swaminathan, is a clinical research midwife at MTW and worked on the GBS2 study. Louise Swaminathan said: “It is important to base decisions on sound evidence and this gives confidence to doctors to not give unnecessary antibiotics. We need to make the best decisions for the patient. Strong antibiotics given to babies target bad bacteria, but also kill off healthy bacteria in the gut which can lead to stomach upset or diarrhoea and may lead to longer-term health issues.”

Professor Llewelyn concludes: “Antibiotics were used within the NHS before we understood the importance of AMR or the mechanisms behind it. We need evidence about how to use antibiotics effectively and safely in clinical practice while causing minimal harm to the patient through AMR.”