1. Maximising the use of diagnostic technology to tackle the challenge of antimicrobial resistance
Fiona Carragher FRCPath @DepCSOFiona
Deputy Chief Scientific Officer for England
November 2018

2. The rising tide of Antimicrobial resistance
Infections are increasingly developing that we cannot treat with a rapid spread of multi-drug resistant (MDR) bacteria
We may not be able to treat or prevent everyday infections or disease
Existing antimicrobials are becoming less effective
Bacteria, fungi, viruses are adapting naturally and becoming increasingly resistant
Inappropriate use of these medicines
All-time low in new antibiotics being developed
Recognising this is a ‘one health’ agenda
WHO priority list of 12 resistant bacteria that pose the greatest threat to human health

3. The future if we do not act now
By 2050: more deaths from resistant infections than cancer

4. The UK AMR Strategy: a tripartite approach
Antimicrobial resistance arises when the organisms that cause infection evolve ways to survive treatment. Once standard treatments are ineffective, it is easier for infections to persist and spread.
The inappropriate use of anti-infectives and antimicrobials in both human and animal medicine, and unintentional exposure, for example through environmental contamination and food, is rapidly accelerating the pace at which it develops and spreads.
By 2030, the global human consumption of antibiotics is forecast to rise by more than 30% and animal antimicrobial use is also expected to increase, especially in low- and middle-income countries.
The rise and spread of antimicrobial resistance is creating a new generation of ‘superbugs’ that cannot be treated with existing medicines.
Already, antimicrobial resistance is estimated to cause 700,000 deaths around the world each year. That figure is predicted to rise to 10 million, alongside a cumulative cost of $100 trillion, by 2050 if no action is taken.
The 2013–2018 strategy and UK Government ambitions on antimicrobial resistance have helped reduce antibiotic use in both humans and food-producing animals
The UK programme is currently focused on delivery of those ambitions through 4 core programmes (infection, prescribing, diagnostics, animal use) and 3 supporting work-streams (surveillance and behaviour, education and training, global and domestic research and drug pipeline activity).

5. The role of diagnostics in AMR
Independent review of Antimicrobial Resistance - Jim O’Neill
Diagnostics are critical to the appropriate use of antimicrobials
Step change in the way technology is incorporated into the decision making process
Currently many decisions are based on an empirical diagnosis
Rapid point of care diagnostics enabling a precise, timely diagnosis
Decision support approach to drive change in prescribing
“I call on Governments to ensure that, by 2020, all antibiotic prescriptions will need to be informed by …. a rapid diagnostic test wherever one exists” Jim O’Neill
“Having rapid, low-cost, and readily available diagnostics is an essential part of the solution to this urgent problem.” Dr Margaret Chan, DG, World Health Organisation

6. Which diagnostics could be used in AMR?
Bacterial or viral
Bacterial type
Resistance (which antibiotics must I not use?)
Susceptibility (which antibiotics can I use?)
Recognising there is also a role for host response biomarkers
From O’Neill

7. Diagnostics – the signalling system for the NHS
Direct patients and patient flows so that the right people get to the right place at the right time
Ensure treatment and management is efficient, effective and coordinated
Have a critical role in prioritising activity so that services are resilient and sustainable
Fundamentally shape the health economics of particular patient pathways

8. UK AMR Diagnostics - Vision
Maximising the use of high quality value driven diagnostic technology to tackle the challenge of antimicrobial resistance
The UK AMR diagnostic collaborative through system leadership, system and strategic alignment, local connectivity and UK oversight will ensure:
A rapid and flexible diagnostic offer tailored to the setting
Development of national standards of quality and safety for point of care diagnostics
Pursuing innovation by leveraging system partnerships and health innovation funding bodies

9. UK AMR Diagnostics – Strategy
Ensuring that the right test is available at the right place at the right time.

10. Diagnostics – the current view of the system
Standards
Levers & Incentives
Inappropriate use (diagnostics)
Service quality
Adoption
Commissioning arrangements
Data Infrastrucure
Routes to use
Complexity of system
External Assurance
Models of provision

11. UK AMRDC- Providing a single point of focus for the system
System Leadership
Local connectivity & good practice
Strategic Direction
UKAMRDC
System
Alignment
Nat’l Policy, Levers, Incentives,
UK Oversight

12. UK AMR Diagnostic Collaborative Programme
Value proposition
Diagnostic Stewardship
One Health
Innovation
Policy and Communication aligned to current policy and regulatory environment
System partners
Public Health England
Health Education England
DEFRA
Key areas of focus
Devolved Administrations

13. Diagnostic stewardship- definition
Coordinated professional guidance and interventions to improve patient understanding, care and management through the appropriate use of clinical assessment and clinical scoring algorithms, biomarker tests and/or microbiological diagnostics to guide therapeutic decisions or screening strategies.
It should promote appropriate, timely diagnostic testing, including specimen collection, and pathogen identification and accurate, timely and audited reporting of results to guide care. It should discourage unnecessary diagnostic testing and the use of tests that yield misleading results.
Diagnostic Stewardship should utilize microbiological data, including accurate and representative AMR surveillance data to inform local treatment guidelines, and AMR control strategies, and should be an integral component of measures to improve antimicrobial stewardship and infection prevention and control
Diagnostics as part of the multi-professional approach ‘a seamless partnership between laboratories, pharmacists and clinicians’
WHO 2016: Diagnostic stewardship
A guide to implementation in antimicrobial resistance surveillance sites

14. Laboratory as part of the multi-professional approach
Patient presents
Condition postulated
Test ordered
Sample Collection
Sample processed
Reporting
Intervention selected
PRE-ANALYTIC
POST-ANALYTIC
ANALYTIC
DIAGNOSTIC INPUT

15. UK AMR DC 18/19 areas of focus -Diagnostic Stewardship
Use of biomarkers eg CRP/Procalcitonin in acute settings or as POCT in the community
Quality improvement approach to diagnostics within the blood culture pathway enabling timely review of antibiotic therapy
Urinary infections: Tackling inappropriate use of urinary diagnostics and focus on the urine culture pathway
UK wide building on good practise, driving quality improvement and addressing variation

16. The CRP Landscape Variation in adoption across UK
NICE [CG191] Pneumonia in adults: diagnosis and management
For people presenting with symptoms of lower respiratory tract infection in primary care, consider CRP POCT if after clinical assessment a diagnosis of pneumonia has not been made and it is not clear whether antibiotics should be prescribed.
Do not routinely offer antibiotic therapy if CRO < 20 mg/L
Consider a delayed antibiotic prescription if CRP mg/L
Offer antibiotic therapy if the CRP >100 mg/L
Variation in adoption across UK
No coherent commissioning approach
Barriers to adoption emerging
Economic case for investment being made at local level
Training and support for clinicians
Quality oversight of testing

17. Learning from the CRP pilot studies
Data from in total
Implementation stage
6 x confirmed implementation programs
18 x pilot study phase
3 x scoping phase pilot/implementation
Settings
18 x GP (from individual to multiple)
2 x elderly care
1 x paediatric
3 x emergency setting

18. ToDipOrNotToDip aims to:
Combines clinical evidence with quality improvement science to improve the management of UTI in care home residents and has delivered sustained improvements in safe and effective patient care.
ToDipOrNotToDip aims to:
Improve awareness of AMR, AKI & prevention and diagnosis of UTI by care home staff
Stop inappropriate dipstick testing of urine samples
Reduce inappropriate / increase appropriate antibiotic prescribing for residents
Improve communication about suspected UTI between GPs and care home staff
Ensure appropriate sending of urine samples for culture and sensitivity test
Implementation:
Education sessions and resources for care home staff
Recommend use of clinical assessment not urine dipsticks to diagnose UTI
Primary care clinicians following local guidelines to treat UTI appropriately
Using an assessment and standard communication tool with primary care clinicians
Use of red top bottles which contains boric acid for preserving the urine
Uniting the science and practice of clinical improvement

19. #ToDipOrNotToDip
Improved appropriate management of UTI, and reduced inappropriate use of antibiotics
56% reduction in the number of residents prescribed antibiotics
67% reduction in the number of antibiotic prescriptions
Improved the management of Catheter Associated UTI
Reduction in E.coli blood stream infections
Reduced calls to primary care clinicians for inappropriately diagnosed UTI saves time
Uniting the science and practice of clinical improvement

20. The importance of the end to end blood culture pathway

23. Blood culture pathway – next steps
November: UK wide survey of blood culture against UKSMI guidance
Gain a system wide understanding of current laboratory practice in relation to quality and unwarranted variation
Enable the UK ADC with partners to develop mechanisms to improve services
In collaboration with NHS Improvement GIRFT (Getting It Right First Time) programme
Opportunity to align with UKAS inspection regime

24. Innovation: challenging ourselves to go further, faster
Disruptive approaches – What else can we learn from:
Evolving technologies
Big data, analytics & AI
Animal Health
Handheld ‘lab on a chip’
Developing world approaches
Point of care testing
Biomarkers, immunology, genomics
Other scientific specialisms
High throughput genomic technologies

25. Integration and collaboration is everything
Academia
NHS
Patients
Industry
International
Area of maximum advance
INVENTION
EVALUATION
ADOPTION
DIFFUSION

26. Innovation work stream – next steps
5th December: Welcome Trust
Engagement event to gain an understanding from industry and innovators
• The current challenges when accelerating usage of solutions developed by industry
• The challenges and potential solutions to feed into national policy
• Highlight opportunities for test bed working
31st January:
With all system partners to understand how health regulation, policy innovation, funding, quality, safety and research can support the government’s ambition to embed rapid diagnostics.

27. UK AMR agenda- 2019 and beyond
The government will shortly be setting out a refreshed UK strategy for AMR, this is likely to set out a longer term vision accompanied by a shorter term 5 year National Action Plan
The new plan will take a coordinated approach, setting out challenging ambitions for the next five years and commitments across humans, animals, food and the environment.
For human health this will be aligned to the emerging NHS Long Term Plan

28. Continued Focus on AMR Diagnostics
The Health and Social Care Select Committee released the report from their inquiry into AMR 22nd October 2018
Within this there are specific recommendations relating to diagnostics

29. The system must be responsive
The work of the UK AMR diagnostic collaborative is crucial in ensuring that all the right groups and agencies are working together to address these challenges.
System response
Define the capabilities
Prioritise technologies
Supportive regulatory structure
Systematic approach to rapid adoption
Streamline & develop evidence base
Connected data across care pathways
Define the capabilities that new technologies should deliver in different settings
Prioritise technologies which have the potential to both assess the pathogen as well as resistance that can inform and reduce antibiotic prescribing
Encourage industry to focus on the development of multiplex systems reflecting the clinical presentations that are often affected by multiple organisms
Ensure that regulations in relation to licencing facilitate rapid adoption of priority technologies,
Streamline the development of the evidence base for many tests and fast track clinical trial data to aid implementation into clinical use
Ensure the availability of test results both to support clinical decision making and epidemiology.

30. The UKAMRDC Working in partnership