Corporate report

APRHAI: summary of activities and recommendations, January to December 2019

Published 13 May 2021

Introduction

APRHAI is the Department of Health and Social Care’s independent, non-executive advisory committee, which provides practical and scientific advice to the government on minimising the risk of healthcare associated infections and addressing antimicrobial resistance. In making recommendations, the committee takes account of the relevant work of other expert groups in the human and veterinary fields.

APRHAI plays a crucial role in the development of the UK’s Antimicrobial Resistance (AMR) strategies. It advised on the development of the UK’s 20 year vision for AMR and the National Action Plan (NAP) 2019 to 2024, which were published on 24 January 2019.

In 2019, APRHAI’s work focused on supporting delivery of the NAP across the 4 countries of the UK and, in particular, on work to achieve the 5 year human health measurable ambitions. The committee considered the following aspects:

• strengthening the role of the committee as a UK-wide body, with input from all the UK health administrations, dedicating meetings to reviewing data and progress in the 4 countries
• providing guidance to national organisations working towards the achievement of the NAP targets
• understanding lessons learned from the implementation of the previous 2013 to 2018 AMR strategy
• supporting the identification of AMR research priorities

The full committee meets 3 times each year. This report provides a high-level summary of the committee’s work in 2019. See APRHAI meeting minutes.

Annex A contains a glossary, with a brief explanation of the terms used in the report and the APRHAI membership can be viewed in annex B.

1. APRHAI main activities in 2019

The committee met on 3 May, 28 June and 27 September 2019. See detailed information on discussions and actions agreed by the committee

The issues discussed and main activities carried out in 2019 are summarised below.

The UK’s vision for AMR by 2040 and the 5 year national action plan

The UK AMR 2040 vision and the NAP were launched in January 2019. The committee agreed that its advice will be crucial in supporting the government to achieve the 2040 vision and 5 year ambitions. The role of diagnostics was also discussed and the need to challenge and support progress of this aspect of the NAP.

Healthcare associated infections from a UK wide perspective

England, Scotland, Wales and Northern Ireland surveillance and public health teams presented to the committee the most recent data on infections, and especially the trends in Gram-negative bloodstream infections (GNBSI), which are slowly rising. The committee highlighted how data from all the 4 countries present similar infection patterns and trends that needed further consideration.

Effective interventions on Gram-negative bloodstream infections

A new APRHAI subgroup was launched, focusing its work on assessing the evidence base for the most important/effective interventions to reduce healthcare-associated GNBSI by 50% by 2025 in England. The committee considered it important to provide new recommendations that are responsive to current needs and take into account the evidence base around what works best. The subgroup provided an initial update at the September meeting and then a full report and recommendations will be presented to the committee in March 2020.

Carbapenem Producing Enterobacteriaceae (CPE) – legislation to include carbapenem resistant Gram-negative infections on the list of notifiable organisms within the Health Protection Regulations

Public Health England (PHE) proposed options regarding the addition of causative agents to the Health Protection (Notifications) Regulations, in support of the 5 year UK AMR NAP, and to improve surveillance of infections caused by carbapenem resistant bacteria. Carbapenems are antibiotics that have a broad spectrum of activity against both Gram-positive and Gram-negative bacteria. They are often referred to as ‘antibiotics of last resort’ due to their activity against multi-resistant bacteria. Carbapenem resistance due to the emergence of acquired carbapenemases is of particular concern.

PHE was tasked with providing the technical expertise to facilitate the case to ministers to change the legislation to include “carbapenem-resistant Gram-negative invasive infections on the list of notifiable organisms within the Health Protection Regulations by December 2019”. APRHAI endorsed the most comprehensive approach, requiring notification of acquired carbapenemase-producing Gram-negative bacteria isolated from all specimen sites. This will allow recording of both colonisation, invasive and other infections, with the addition of mandating the quarterly reporting of the number of rectal screens performed for carbapenemase producing organisms. This recommendation was communicated to the DHSC in December 2019 (see Section 2, Recommendations made by APRHAI).

Lessons learned from the evaluation of the 2013 to 2018 UK AMR strategy and understanding variation in primary care prescribing

The London School of Hygiene and Tropical Medicine presented main findings and highlights from their evaluation of the implementation of the UK AMR strategy. Examples of implementation from all 4 UK countries were discussed, highlighting the differences in local implementation across the UK and variations in terms of strategies and outcomes. The committee agreed that it was important to better understand variation in prescribing as a variable with potential effects on the delivery of the strategy itself and agreed to launch a new task and finish subgroup. This new APRHAI subgroup assesses prescribing practices and the complexity of antibiotic prescribing in primary care, the role played by variation and heterogeneity in prescribing practices in reducing antibiotic consumption and if a best practice statement can be developed. The subgroup produced a report in September and a final report and recommendations will be presented to the committee in 2020.

Antibiotic prescribing from a UK-wide perspective

England, Scotland, Wales and Northern Ireland public health teams presented to the committee data and trends on antibiotic prescribing in primary care (that is, GP practices) and secondary care (that is, hospitals) noting how, overall, there is a decrease in antibiotic prescribing across the system. The committee agreed that there is a varied and complex landscape in terms of differences in prescribing between primary and secondary care, in the use of specific antibiotics and in duration of antibiotic treatments, all factors that need further consideration and to be monitored by the committee on a regular basis. It was agreed that APRHAI will continue to keep antibiotic prescribing trends under review.

Developing and testing innovative models for the evaluation and purchase of antimicrobials

This project is led by the National Institute for Health and Care Excellence (NICE), the National Health Service England and Improvement (NHSE and NHSI) with oversight from DHSC and is a commitment in the UK NAP. The project aims to demonstrate the feasibility of innovative models that pay companies for antimicrobials, based primarily on a health technology assessment of their value to the NHS as opposed to the volumes used. DHSC, NICE and NHSE and NHSI asked for expert advice from the committee, The committee endorsed this approach and agreed to support the project.

Behavioural analysis and stakeholder consultation: interventions to reduce antibiotic prescribing in primary care

PHE’s Behavioural Insights team presented its programme of work on antibiotic prescribing, using behavioural science tools to identify and map behaviours and publicly available interventions. They identified where change needs to occur, as well as gaps and opportunities in current interventions which could be addressed. Specifically, the work is focused on Exploring the implementation of interventions to reduce Antibiotic use and Catheter associated urinary Tract infections (ENACT project). They noted that results demonstrate that there are a number of publicly-available effective antimicrobial stewardship behavioural interventions. The committee discussed with the team how the system of implementing interventions could be better coordinated, streamlined and strengthened and that there is room for individual programme improvement, following behavioural science principles. The committee agreed to the need for a better utilisation of evidence-based behavioural science tools to underpin the implementation of effective interventions and this will be addressed by the APRHAI behavioural interventions and implementation science subgroup, which was launched during this same meeting.

The role of public facing activities: PHE’s Keep Antibiotics Working campaign

The PHE Marketing team presented PHE’s antibiotic awareness campaign “Keep antibiotics working” aimed to alert the general public to the risks of AMR and reduce their expectations for antibiotics. It also supports healthcare professionals who prescribe antibiotics by providing helpful tools for conversations with patients when antibiotics are not required. The results from the evaluation of the 2018 campaign were discussed. The committee considered it important to assess the outcomes of the campaign and agreed that an in-depth evaluation would be needed to better understand the role of social marketing in support of the AMR strategy and that recommendations would be developed and shared with DHSC for an in-depth evaluation of the 3-year Keep Antibiotic Working campaign strategy (see Section 2, Recommendations made by APRHAI).

Ways to engage the public with AMR

The University of Glasgow discussed with the committee ways to engage the public across the system and with relation to the UK AMR NAP 2019 to 2024. It was highlighted how an engagement strategy needs to be thought of in systemic terms to be effective. The committee agreed that in the last 5 years a wide range of evidence has been produced on the role played by behavioural sciences in tackling AMR, however this has not so far come to APRHAI for consideration and that there is a clear demand for behavioural aspects to be more fully understood and appraised. The committee agreed to launch a new APRHAI behavioural subgroup, with the aim to explore and assess gaps/opportunities presented by behavioural sciences tools and how to operationalise the behavioural sciences input into interventions that can be implemented. The subgroup will report back to APRHAI in 2020.

Current Gram-negative bloodstream infections interventions from a UK-wide perspective

The 4 UK Administrations presented their work on GNBSI interventions. The committee fed back on the importance of measuring and reporting on GNBSI in a unified way and, if possible, to have a key measure (that is, a single number) for reporting on bacterial infections, that can be measured against NAP targets. The committee agreed that there is an opportunity to standardise measures that would be highly beneficial in supporting the NAP targets and agreed that this could be discussed at the 4 nations surveillance group’s next meetings and that the group will produce a paper detailing metrics and methods for reporting on GNBSI, to be presented to the next AMR Delivery Board in February 2020.

Infection prevention and control strategies and identification, prevention and treatments of sepsis

Mervyn Singer (University College London) discussed key aspects in the identification and treatment of sepsis, which is defined as an organ dysfunction triggered by a dysregulated host response to infection, while Matt Inada Kim (Hampshire Hospitals NHS Foundation Trust) discussed with the committee a proposed combined national approach on Infection prevention and control (IPC). There are a number of specific IPC workstreams already active, but a combined infection strategy would be more capable of addressing the complexity of the issue. In terms of sepsis, there was a discussion on the need to standardise and agree a single definition, as current differences make it difficult to assess and test for sepsis effectively. The committee agreed that consensus needs to be achieved at a wider level, moving forward, opening up to other organisations involved, including NICE and Royal Colleges, and that a risk-based approach should be developed. This will support the work of all healthcare staff managing sepsis. The committee agreed also that there is an overall lack of evidence, this includes understanding comorbidities and unintended consequences of sepsis treatment. In order to address these aspects, the committee asked the NHSE AMR Programme Board to return to the committee at one of the 2020 meetings to present the NHS infection control strategies and identification and treatment of sepsis.

Incidence and mortality in AMR infections in the UK

PHE presented a paper to update the committee on the work carried out by all 4 UK health administrations and coordinated by PHE to develop consistent methodologies for reporting on the number of antibiotic resistant infections and the number of deaths in patients with antibiotic resistant infections. An overview of methodology and bug/antibiotic combinations used was presented, in particular regarding colistin antibiotic susceptibility test results. The methodology is based on the Cassini study (2018) ^{[footnote 1]}, where a methodology is described for estimating attributable deaths and disability-adjusted life-years. PHE asked APRHAI to consider and provide feedback on whether or not to include colistin in the approach to estimate the AMR burden. It was agreed that it was important to follow the Cassini methodology, which is being used at international level, but to leave out colistin testing for UK purposes. The committee discussed more generally the methodology to measure progress against the NAP targets and it was agreed to produce both absolute numbers and estimated numbers (as per Cassini) to monitor progress.

Antibiotic policy and availability

DHSC provided an update on antibiotic policy and availability and it was agreed by the committee that annual/biannual meetings should continue to take place regularly. Representatives from DHSC procurement, NICE, PHE and NHSE Commercial Medicines Unit (CMU) met in September and discussed use of older generation antibiotics, supplier issues and ways of addressing potential future shortages, with an agreement that organisations can improve working together and with manufacturers.

2. Recommendations made by APRHAI in 2019

Recommendations on legislation to include carbapenem resistant Gram-negative infections on the list of notifiable causative agents within Health Protection Regulations

The committee endorsed the requirement for notification of acquired carbapenemase-producing Gram-negative bacteria isolated from all specimen sites – this will allow recording of both colonisation, invasive and other infections.

Together with the addition of mandating the quarterly reporting of the number of rectal screens for carbapenemase producing organisms performed, this should be adopted at UK-wide level to ensure a strengthened and integrated approach to the prevention and control of these priority infections and that the Devolved Administrations should consider ways of adopting these recommendations in each country, according to local legislation.

Recommendations on the evaluation of PHE’s ‘Keep Antibiotic Working’ awareness campaign

The committee agreed that an independent, in-depth evaluation of the PHE campaign would be beneficial to better understand the role of social marketing in support of the AMR strategy and whether there is scope to use social marketing to implement the national action plan.

The committee also recommends that the independent evaluation should address, where not covered by PHE’s own evaluation, the following areas:

• a cost evaluation analysis of the 3 years of the campaign (2017 to 2019)

• exploration of possible correlation with prescribing data trends over the same period

• public and professional awareness of the key messages

• if results in terms of impact of the campaign support for the case for further campaigns

• if the campaign can be used as a case study for other countries

Annex A – Glossary

Term	Definition
Antimicrobial	A drug that selectively destroys or inhibits the growth of microorganisms. Sometimes referred to as an ‘antimicrobial agent’. Examples include antibiotics (also known as antibacterials) antiviral and antifungal agents. In the context of this document references to antimicrobials includes anti-infectives where that would be relevant in the context of the text.
Antibiotic resistant bacteria	Bacteria with the ability to resist the effects of an antibiotic to which they were once sensitive.
Antimicrobial resistance (AMR)	Occurs when the microorganisms that cause disease (including bacteria, viruses, fungi and parasites) cease to be affected by the drugs we use to kill them and treat the disease.
Antimicrobial stewardship (AMS)	A key component of a multifaceted approach to improve the safety and quality of patient care whilst preventing the emergence of antimicrobial resistance. Good antimicrobial stewardship involves selecting an appropriate drug and optimising its dose and duration to cure an infection while minimising toxicity and conditions for selection of resistant microbes. Good AMS includes a review of the continuing need for antibiotics following clinical diagnosis and documented actions to stop, continue or change antimicrobial treatment.
Carbapenems	Broad-spectrum antibiotics, often used as the last line of treatment for hard to treat human infections caused by Gram-negative bacteria.
Carbapenemese Producing Gram=negative Organisms	A group of bacteria that is resistant to carbapenems class of antibiotics.
Disease burden	This includes the number of infections in the population and also includes economic costs like treatment costs for hospital admissions and the cost to health in terms of mortality and morbidity
Enterobacteriaceae	A family of Gram negative bacilli that contains many species of bacteria that normally inhabit the intestines. Enterobacteriaceae, that are commonly part of the normal intestinal tract flora, are referred to as coliforms.
Gram-negative bacteria	Those bacteria that do not retain crystal violet dye in the Gram-staining procedure. They can cause many types of infection and include E. coli and Pseudomonas aeruginosa.
Healthcare associated Gram-negative blood stream infection	A laboratory-confirmed positive blood culture for a Gram-negative pathogen in patients who had received healthcare in either the community or hospital in the previous 28 days.
‘One-Health’ approach	Collaborative multi-disciplinary work at local, national, and global levels to attain optimal health for people, animals and the environment.
Pathogen / Pathogenic	An infectious agent (bug or germ), a microorganism such as a virus, bacterium, or fungus that causes disease in its host.
Primary care	Services provided by GP practices, dental practices, community pharmacies and high street optometrists.
Secondary care	Covers acute healthcare, either elective care (planned specialist medical care or surgery, usually following referral)or emergency care.
Sepsis	Is a serious complication of an infection. Without quick treatment, sepsis can lead to multiple organ failure and death.
Surveillance	Systematic collection of data from the population at risk, identification of infections using consistent definitions, analysis of these data and dissemination of the results to those responsible for the care of the patients and to those responsible for implementation of prevention and central measures.

Annex B – APRHAI membership

Member	Profession	Organisation
Professor Alistair Leanord (Chair) Note: appointed in March 2019)	Professor of Microbiology and Director of the Scottish Microbiology Reference Laboratories	NHS Greater Glasgow and Clyde
Professor Andrew Peter Wilson (Deputy Chair)	Professor of Microbiology & Consultant Microbiologist	UCLH NHS Foundation Trust
Ms Jane Binyon	Lay Member
Dr Nicholas Brown	Consultant Medical Microbiologist	Addenbrooke Hospital, Cambridge
Dr Kieran Hand (note: appointment ended in August 2019)	Consultant Pharmacist of antiinfectives	University Hospital Southampton
Ms Judy Potter (note: appointment ended in June 2019)	Lead Nurse for Infection Control & Tissue Viability Service and Joint Director of Infection Prevention & Control	Royal Devon and Exeter NHS Foundation Trust
Professor David Livermore	Professor of Medical Microbiology	University of East Anglia
Professor Michael Moore	Professor in Primary Health Care Research	University of Southampton
Professor Peter Moss	Consultant in Infectious diseases	Hull & East Yorkshire Hospitals NHS Trust
Dr Sarah Tonkin-Crine	Chartered Psychologist, Health Psychologist	Nuffield Department of Primary Care Health Sciences, University of Oxford
Professor Neil Woodford (note: appointment ended in November 2019)	Molecular Microbiologist, Head of Antimicrobial Resistance and Healthcare Associated Infections	Reference Unit (AMRHAI) Public Health England
Dr Laura Shallcross (note: appointed in June 2019)	Consultant in Public Health Medicine. Institute of Health Informatics	University College of London
Karen Shaw (note: appointed in June 2019)	Director of Infection Prevention and Control	UCLH NHS Foundation Trust
Prof Philip Howard (note: appointed in June 2019)	Consultant Antimicrobial Pharmacist	Leeds Teaching Hospitals NHS Trust
Neil Wigglesworth (note: appointed in June 2019)	Director of Infection Prevention and Control	Guy’s & St Thomas’ NHS Foundation Trust
Martin Llewelyn (note: appointed in June 2019)	Professor in Infectious Disease	University of Sussex

1. Cassini, Alessandro, Strauss, Reinhild and others. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis, The Lancet Infectious Diseases, Volume 19, Issue 1, 56 to 66 ↩