List of questions

2397: what needs to be done to implement CRP POCT in primary care in UK?

2398: 1. Can CRP be used to reduce antibiotic prescribing in children and if yes, which cut-offs can be recommended and what needs to be considered?

2399: 2. Could you please provide a list of what needs to be considered when using CRP in elderly to reduce antibiotic prescribing or avoid unnecessary referral to the hospital?

2397: Not every CCG or trust sees the same value in testing due to cost of testing.

2398: Looking for clinical guidance for the best way to impact AMR using CRP testing

2399: Looking for clincial input with how best to utilise CRP and give the most benefit.

What are the barriers to adoption of point of care tests?

Community/Primary care versus Secondary care setting in testing and early diagnosis.

What emerging approaches can be used to enhance the efficacy of antimicrobial biologics for oral or parenteral administration?

Large peptides or small proteins with antimicrobial activity, like the bacteriocins, can have potent antimicrobial activity and be well suited to topical administration. This may limit the target clinical indications that they can be used for, but previously issues have been reported with stability and immune responses during systemic administration. What new approaches can be used to increase the efficacy of such agents for systemic use?

How do we leave the era of empiric antibiotic treatment regiments and move into personalized evidence-based treatment of infectious diseases?

A rapid, reliable and cost-effective diagnostic device that can be used at the point-of-care, could perhaps be a solution to the emerging AMR crisis. In particular, if it can be used in primary care were most of the antibiotics are prescribed.
Astrego Diagnostics is developing a system that could fulfill all these criteria, but to our surprise we get very mixed responses when presenting it to the community.

As a first point-of-care application, we aim for urinary tract infections (UTI). How should the method be implemented when many primary care settings only meet 0-2 patients/day with UTI symptoms?

A rapid, reliable and cost-effective diagnostic device that can be used at the point-of-care, could perhaps be a solution to the emerging AMR crisis. In particular, if it can be used in primary care were most of the antibiotics are prescribed.
Astrego Diagnostics is developing a system that could fulfill all these criteria, but to our surprise we get very mixed responses when presenting it to the community.

2393: 1. How to use in vivo models to quantify the effect of the immune system on bacterial killing? Both questions are linked, so could be part of a single session.

2394: 2. What in vivo and in vitro models can be used to quantify the effect of the immune system on the emergence of resistance? Both questions are linked, so could be part of a single session.

2393: Immunotherapy for bacterial infections are an alternative to traditional antibiotics treatment. What biomarkers/immune cell could predict immune-driven outcome in preclinical models and how can they be used to translate the effect to predict a dose for the clinic?

2394: What role does the the immune system play in the emergence of resistance and how can that be quantified? What in vitro and in vivo models could be used to assess the impact of the immune system and immunotherapies on resistance and resistance mechanisms?

Should novel antibacterial drugs with low propensity for engendering bacterial resistance be used in place of traditional antibiotics or be reserved for use of last resort?

Misuse of antibiotics can lead to the development of antibiotic resistance, which adversely impacts morbidity, mortality, length of stay and cost.
If a new drug gains approval, healthcare systems may reserve it as an intervention of last resort in case resistance develops. Prescribers can only witness the impact of a chosen therapy according to patient response in the short term, they cannot necessarily see longer term benefits on the local environment resulting from careful stewardship.

What strategies to circumvent the Gram negative bacterial cell envelope can be reliably employed during the development of novel antibiotics in order to deliver them to their targets

There are multiple potential drug targets in bacteria but the challenge in drug discovery is getting access to the target. Gram negative bacteria have complex cell envelopes that act as a barrier or restrict access through porins, in addition bacteria have numerous efflux pumps to remove unwanted molecules that are able to translocate across the membrane in the cell.

How can diagnostic providers work better with academics, clinicians and health authorities to best respond to the emergence of fungal resistant strains?

Since the first outbreak of a multi-drug resistant fungal pathogen in a major NHS hospital in London in 2016, there has been a lot of media interest and coverage on the emergence of C. auris. The CDC in the US recently declared this an urgent threat to public health on a global level. Like antibiotic resistance, better stewardship on the use of antifungals in medicine and agriculture forms a good preventative strategy. In terms of diagnosis, however, one of the biggest issues lies in the lack of a good diagnostic solution that quickly identifies strains that are resistant. There are platforms and assays available that are able to detect the presence of bacteria or viruses, but this isn't a straightforward case for fungi detection and differentiation. This leads to the question poised on how diagnostic providers can help address this better via a collaborative approach between stakeholders with vested interest and concern.

What kind of in vitro and in vivo models can be used to identify and progress non-canonical antitubercular drugs?

Mycobacterium tuberculosis remains one of the deadliest infectious diseases. Despite of the new antitubercular drugs recently progressed to clinical trials, new drugs targeting multi-drug resistant tuberculosis are needed. We are interested in developing new alternative anti-tubercular drugs based in host-pathogen interactions and/or non-conventional antibiotics.

Which immunologic components are required to maintain a latent infection and prevent reactivation? How does the bacterium evade host antimicrobial defenses and survive in the face of a strong immune response?

In response to infection with Mycobacterium tuberculosis, most persons mount a robust immune response, culminating in the formation of a granulomatous lesion that apparently contains the infection. In some cases, the infection reactivates to cause active disease.

How do we best exploit AI/machine learning to adapt anti-microbial peptides for improved efficacy, target range and other key properties?

We are in a current multi-disciplinary collaborative programme to adapt a 51 mer peptide member of a novel antimicrobial structural class to alter and enhance relevant properties. We face constraints of computer processing power and throughput related to amino acid chain length. We are interested to explore ideas how peptide structural features, patterns, templates and/or alternate algorithms might be employed to accelerate our learning and applications.

what unique issue is not being funded in relation to AI/AMR

IUK can provide funding in the development of AMR and needs to understand where to best any funds its may have available

What is the best way to get proteins into the cytoplasm of Gram negative or Gram positive bacteria?

Also interested in increasing the efficiency of entry of small molecule antibiotics

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• Broad spectrum antibiotics v Narrow spectrum antibiotics: Where does the future lie?

Is it worthwhile developing narrow spectrum antibiotics

• What are the go and no-go selection criteria during hit-to-lead and lead optimization process

Small molecule discovery process

How can we minimise development of resistance?

How are in vitro Frequency of Resistance and in vivo / clinical resistance data related?
What level of in vitro resistance (FoR) is the minimal acceptable?
What strategies can be adopted at the research stage to minimise
resistance development?

2377: How would you identify a particular porin involved in the uptake of a drug across the outer membrane of Gram-negative bacteria?

2378: How would you quantify the permeability of a drug across the outer membrane of Gram-negative bacteria

2377: Receptor mediated porin transport (e.g. by TonB receptors) exist on the outer membrane of Gram-negative bacteria. Selective uptake of a drug by such a transport system would be highly advantageous.

Both questions are linked, so could be part of a single session.

2378: Understanding the permeability of a drug via a selective porin in bacteria (including in knockouts) would be highly advantageous.

Both questions are linked, so could be part of a single session.

How does a multiplex approach to infectious disease diagnostics help antimicrobial stewardship initiatives?

Randox Laboratories have developed a patented Biochip Array Technology (BAT), which is able to detect multiple targets from a single patient sample. This technology has been utilised on a fully automated platform (the Vivalytic), to bring infectious disease multiplex testing to the patient-side. A key intention is to facilitate informed prescribing, and in turn antibiotic stewardship. Understanding how scientists will use the information the BAT provides will be key to ensuring this technology reaches a market with maximal patient outcomes.

What disruptive therapeutic or technology approaches would allow us to better treat antibiotic-resistant Pseudomonas aeruginosa and Acinetobacter baumannii infections?

New treatments to treat Pseudomonas and Acinetobacter infections have proven to be particularly challenging. Both bacteria species represent serious unmet needs in the AMR area. New approaches are therefore urgently needed to address the current and future therapeutic gaps for these important bacterial pathogens.

How can academia, the testing lab, the clinician and industry integrate faster methods, together with highly accurate phenotypic microbial identification and susceptibility testing methods?

Accuracy is key in identifying and appropriately treating infection. Faster results are important too. Current infrastructure can limit the uptake of novel or complementary tests/systems, in the lab and at the point of care.

Attendees to comment on their perceptions of the relative benefits and challenges of different methods (e.g. phenotypic/genetic) and perceived barriers to adoption