PACE Unmet needs in antimicrobial diagnostics

What are the greatest unmet needs in antimicrobial diagnostics?

Insights from our consultation with frontline healthcare professionals and key opinion leaders

WHAT ARE THE GREATEST UNMET NEEDS IN ANTIMICROBIAL DIAGNOSTICS?

Diagnostic innovation to tackle antimicrobial resistance Misuse and overuse of antimicrobial drugs are the main drivers of antimicrobial resistance (AMR) – one of the biggest challenges we face as a society. With AMR developing faster than the speed of our scientific discoveries, we urgently need new approaches to keep up.

PACE is a £30 million initiative to help drive early-stage innovation and progress new developments needed to combat AMR. Our second funding round, launched in 2024, invites the research ecosystem to consider diagnostic innovations that could help to:

Reduce inappropriate antibiotic prescriptions

Provide faster results that indicate which antibiotic should be used

Catalyse the move to personalised, narrow-spectrum treatments

PACE is a £30 million initiative to help drive early-stage innovation and progress new developments needed to combat AMR.

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WHAT ARE THE GREATEST UNMET NEEDS IN ANTIMICROBIAL DIAGNOSTICS?

Exploring the unmet needs of antimicrobial diagnostic innovation We ran a consultation across 2024 to ensure we’re addressing the needs of those who routinely prescribe antimicrobials for the management of microbial infections on the frontline of patient care.

This included: • Interviews with key opinion leaders to understand the challenges faced by healthcare professionals and diagnostic developers • A survey with healthcare professionals working in community, primary and secondary care to identify where improvements are most needed, and explore ideal characteristics for novel diagnostic tests • Desk-based research into current clinical practice and pathways, the funding landscape and the potential of emerging technologies

We focused on the indications that present both the highest antibiotic consumption and the highest burden from AMR:

What could innovation in antimicrobial diagnostics achieve?

What are some of the barriers to impact in antimicrobial diagnostics?

• Urinary tract infections (UTIs) • Lower respiratory tract infections (LRTIs) • Blood stream infections (BSIs) including sepsis Our consultations were primarily with stakeholders based in the UK – while the insights gathered will be broadly reflective, each UK region will have its own nuances with respect to infrastructure, causative organisms and infection control. The outputs from our consultations were combined with the output of other studies that have assessed the diagnostic needs globally* and used to inform the final shape of the funding round.

Thank you to everyone who took part in our consultation – the expertise and experience shared have been immensely helpful in shaping our funding round so that it can be as impactful as possible.

We’re pleased to share the insights with you in this report. We hope it will spark new ideas for how we, as a research community, could help to drive progress against AMR.

Prolonged lifespan of antibiotics

£

High cost compared to antibiotic prescription

Better patient outcomes

Uptake of new tests in healthcare and laboratory settings

Precision medicine

Balancing individual need with societal need to reduce antibiotic use

Patients matched to right antibiotic faster

Integration with limited capabilities and inflexible infrastructure

Spread of infection prevented

Specialist training for test delivery or interpretation

We focused on the indications that present

*Barrass et al, 2022. “Horizon Scanning Final Report: Identification of Acute deterioration/Sepsis Technologies.”; Barrass et al, 2021, “Horizon Scanning Final Report: Identification of Respiratory Tract Infection Technologies”; Barrass et al, 2021, “Horizon Scanning Report: Identification of Urinary Tract Infection Technologies” (all NIHR Innovation Observatory)

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WHAT ARE THE GREATEST UNMET NEEDS IN ANTIMICROBIAL DIAGNOSTICS?

What do healthcare professionals think are the greatest needs in antimicrobial diagnostics?

Who took part in our survey?

33 healthcare professionals from across the UK National Health Service including doctors, nurses and pharmacists across community, primary and secondary care.

Each sees on average

64

patients with bacterial infections per month.

uUTI 17%

All agreed there is a significant need

r/cUTI 16%

uUTI 14%

Community Care LRTI 67%

Urinary tract infections (UTIs), including complicated or recurrent UTIs, were listed as important indications in both community and primary care. Sepsis and other blood stream infections (BSIs) ranked highly in secondary care.

Since UTIs and LRTIs are the main drivers of antibiotic use in primary care, these indications are ripe for innovation and improvements to diagnostics*. While tests exist, uptake and implementation in the clinic remains a challenge which could, in part, be due to the lack of innovative solutions in the pipeline that can completely satisfy user and patient needs (**).

LRTI (HA)

BSI

8% LRTI (CA)

8%

Primary Care

for new microbial diagnostics in healthcare.

Across all care settings investigated, lower respiratory tract infections (LRTIs) ranked as the indication with the greatest need for new diagnostic development – with current LRTI diagnostics considered the least impactful of available tests.

Other 7%

LRTI 50%

r/cUTI

25%

r/cUTI 29%

Secondary Care

34%

Sepsis

25%

Figure 1: Greatest unmet need for improved diagnostics by indication and care setting. We asked 6 community care practitioners (left), 14 primary care practitioners (middle) and 12 secondary care practitioners to rank which bacterial infections would benefit the most from better diagnostics. Pie charts represent the % a particular indication was identified as the greatest unmet need for improved diagnostics by professionals within a given setting.

LRTI = Lower respiratory tract infection

Sepsis

r/cUTI = Recurrent/complicated urinary tract infection

Other

uUTI = Uncomplicated urinary tract infection

CA = Community-acquired

BSI = Blood stream infection

HA = Hospital-acquired

*Bertagnolio et al, 2024. doi: 10.1016/S2666-5247(24)00134-4 **Participants could select multiple choices for some questions which, combined with a relatively small participant number, could confound the interpretation of results.

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WHAT ARE THE GREATEST UNMET NEEDS IN ANTIMICROBIAL DIAGNOSTICS?

How are diagnostics used in different healthcare settings?

Our participants answered a series of questions to share their current practice and explore which features should be prioritised when developing diagnostic tests in the future.** Across all settings, participants flagged the time taken to reach an accurate result as an important consideration.

There’s also great potential for tests that can both identify the causative pathogen and provide information about vulnerability to different drugs (Antimicrobial Susceptibility Testing (AST)), to inform clinical decision making.

What is the most frequent use of antimicrobial diagnostics?

What are the most problematic pathogens?

Community Urinalysis (dipstick test) for uncomplicated UTIs

Primary

Urine culture and microscopy for recurrent / complicated UTIs and sputum culture for LRTIs

Secondary

Sputum culture, chest x-ray for LRTIs, blood cultures for BSIs and urine cultures for UTIs

The WHO’s prioritised pathogens* are reflected as most problematic pathogens across healthcare settings.

Even commonly considered easier to treat gram-positive pathogens are considered equally troublesome as critical priority gram-negatives across healthcare settings

What are the biggest barriers to impact of current tests?

Community

Primary

Secondary

Test accuracy, cost of test and time to result Ease of use and need for training also flagged

Time to result

Time to result and limited accuracy

What features should future diagnostics consider?

What features would be most helpful to aid appropriate antibiotic use in future diagnostics?

Community Performance on-site

Pathogen ID, alongside information about Community pathogen’s susceptibility or resistance to different antimicrobials

Primary

Secondary

Accuracy and time to result (ideally less than 10 minutes)

Accuracy and time to result (ideally less than 2 hours) Ability to be performed on-site or near the patient

Primary

Tests to rule out viral vs bacterial infection; pathogen ID alongside information about pathogen’s susceptibility or resistance to different antimicrobials

Secondary

Pathogen ID, alongside information about pathogen’s susceptibility or resistance to different antimicrobials

*Bertagnolio et al, 2024. doi: 10.1016/S2666-5247(24)00134-4 **Participants could select multiple choices for some questions which, combined with a relatively small participant number, could confound the interpretation of results.

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WHAT ARE THE GREATEST UNMET NEEDS IN ANTIMICROBIAL DIAGNOSTICS?

Ideal characteristics of new diagnostic tests: 3 scenarios where focused efforts could make a real difference The unmet needs in diagnostics to manage microbial infections in healthcare settings are complex and vary by stakeholder, setting, geography and indication.

But it’s clear there is huge promise for new, improved diagnostic tests to guide antimicrobial use and help tackle the challenge of AMR. Here, we summarise some of the ideal characteristics that should be considered for diagnostic tests for: 1 | Urinary tract infections (UTIs) 2 | Lower respiratory tract infections (LRTIs) 3 | Blood stream infections (BSIs)

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WHAT ARE THE GREATEST UNMET NEEDS IN ANTIMICROBIAL DIAGNOSTICS?

Scenario

1

Patient presents to primary care or secondary triage with suspected UTI or community-acquired LRTI, with unclear causative pathogen The problem

UTIs and LRTIs are the primary driver of antibiotic use in primary care, with a high rate of unnecessary prescriptions

The need

Rapid, cheap and accurate point-of-care/near patient tests to determine if antibiotic is needed • Detection of infection should fit within normal consultation (<10 min) • Low cost • Easy to use with minimal training or infrastructure

Ideal characteristics

• Fully integrated, or semi-integrated with simple sample preparation • Improved accuracy compared to existing dipstick tests • Ideally suitable for elderly, pregnant or young patients • Align with REASSURED criteria for use in low-resource settings • Could be linked to test for antimicrobial susceptibility or pathogen ID – but one without the other is not helpful to guide treatment • Host- or pathogen-based marker detection lateral flow immunoassay

Example platforms or technologies

• Microfluidic test chips with integrated functions • Closed-cartridge, compact molecular diagnostic systems • Novel technologies • Reduced antibiotic prescribing

Measure of success

• Reduced return visits • Faster infection resolution

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WHAT ARE THE GREATEST UNMET NEEDS IN ANTIMICROBIAL DIAGNOSTICS?

Scenario

2

Patient returns to primary care with unresolved or recurrent UTI or community-acquired LRTI, and/or is referred to secondary care

The problem

To guide treatment, secondary triage needs a way to assess the susceptibility of the causative organism to different antimicrobial drugs

The need

Rapid tests to provide information on pathogen susceptibility

Scenario

Patient in secondary care with a suspected BSI (including (neonatal) sepsis) and needs urgent treatment

The problem

BSIs are life-threatening if not treated quickly, but it can take more than 24 hours for blood culture methods to identify the right treatment. To avoid wasting time, patients are given broadspectrum, often inappropriate antibiotics before test results return

The need

Tests that take <8 hours to detect the infection, the underlying pathogen and the susceptibility profile, and indicate which treatment to use

• Time-to-result available on same day (<6h)

• Time-to-result faster than standard blood culture and ideally to fit within one hospital shift (<8 hours)

• Easy to use with minimal training or infrastructure (to be performed outside of a lab setting) Ideal characteristics

• Could be linked to test for antimicrobial susceptibility or pathogen ID – but one without the other is not helpful to guide treatment

• Straight from sample, without need for pre-culture or extensive sample prep Ideal characteristics

• Detection element could be linked to or de-linked from antimicrobial susceptibility testing (AST) or pathogen ID • Cost-effective, due to high volume of negative blood cultures

• Compact, automated combined ID and phenotypic antimicrobial susceptibility testing (AST) systems • Culture-independent molecular methods – eg nonphenotypic systemics for detecting pathogens and AMR

• Compact, automated combined ID and phenotypic AST systems Example platforms or technologies

• Novel AST systems, including use of metagenomics and AI

Measure of success

Reduced hospital admissions and lengths of stay; reduced recurrence or occurrence of severe disease; faster infection resolution; more appropriate antibiotic prescribing

• Improved, standardised sample collection • Reduced risk of contamination

• LRTI: alternative sample types to current sputum and bronchiolar lavage, such as whole blood or saliva, could have potential

Example platforms or technologies

3

• Culture-independent molecular methods – eg non-phenotypic systemics for detecting pathogens and AMR • Novel technologies

Measure of success

Reduced mortality; faster time to resolution; reduced hospital lengths of stay; faster time to antibiotic de-escalation; increased ratio or narrow- vs broad-spectrum antibiotics

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WHAT ARE THE GREATEST UNMET NEEDS IN ANTIMICROBIAL DIAGNOSTICS?

Bringing PACE to AMR Research Innovation in diagnostics has the potential to make a real difference in the fight against AMR, supporting clinicians to make informed decisions about which drugs to treat their patients.

We’ve identified 3 scenarios (pages 6 to 8) where focused research efforts could address some of the unmet needs of the clinical community.

These scenarios formed the basis of our latest funding round, supporting a diverse portfolio of global early-stage diagnostic projects, ranging from technical feasibility studies to early prototypes, using various technologies.

These diagnostics will target bacterial infections with the highest disease burden and unmet patient need, with the potential to reduce inappropriate prescriptions, provide faster results to indicate which antibiotic should be used and catalyse the move to personalised, narrow-spectrum treatments.

If you share our vision and you’re a researcher with an innovative idea, a potential delivery partner or an investor, we want to hear from you.

To find out more, visit paceamr.org.uk

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Get in Touch If you would like to understand more about PACE or you would like to speak to our team, then please get in touch.

paceamr.org.uk