SYMPOSIUM: Unmet Needs in AMR: Clinical Problems, Scientific Solutions
The Centre to Impact AMR’s Clinical Unmet Needs Working Group hosted a symposium on March 23rd titled Unmet Needs in AMR: Clinical Problems, Scientific Solutions. The purpose of this forum was to bring together clinicians and scientists/engineers to discuss problems and solutions to antimicrobial resistance.
The AMR 2023 Organising Committee:
- Nenad Macesic, The Alfred & Monash University (Chair)
- Anton Peleg, The Alfred & Monash University
- Catriona Bradshaw, Melbourne Sexual Health Centre & Monash University
- Cornelia Landersdorfer, Monash University
- Jeremy Barr, Monash University
Session 1: Improving Diagnosis
CHAIR: Dr Nenad Macesic
Dr Adam Jenney, Alfred Health
For more than 120 years diagnostic microbiology laboratories have dedicated considerable resources, and often their most senior staff, to the detection of AMR. Inexorably, more-and-more is requested of the lab to meet a burgeoning local (and global) resistance problem.
Happily, there has been an explosion of technology that has been taken up into the mainstream, with the promise of more to come. However, it is becoming clear that many structures and functions of the laboratory are going to have to change, and at the same time, new roles and collaborations will need to be created.
A/Prof. Simon Corrie, Monash University
A number of approaches for pathogen typing and antibiotic sensitivity have been recently developed with the aim of providing rapid and actionable information to clinicians and patients. A key challenge in developing and more importantly adopting new tools for infectious diseases and AMR is that needs differ across locale, patient cohort, health systems and also over time (e.g. pandemics). Convergent design approaches can have profound effects on outcomes, by involving key stakeholders throughout the technology conception and development stages, to ensure that the final diagnostic/ biosensor is fit for purpose. Several examples from recent collaborations will be discussed and lessons learned will be highlighted.
Dr Helmut Thissen, CSIRO, Manufacturing
In the future, healthcare providers are expected to be able to rapidly obtain a highly differentiated diagnosis, supporting improved clinical decision making and achieving improved outcomes on many different levels. This differentiated diagnostic capability is also key to better addressing the growing AMR threat. Here the presentation will highlight current limitations and opportunities associated with AMR sensing technologies that can be used not only in the healthcare domain, but also the agricultural and environmental domains. Moreover, the presentation will examine the role that medical devices play in the context of AMR, and highlight opportunities for overcoming the associated infection rates.
Session 2: Gaps in Treatment
CHAIR: Prof. Catriona Bradshaw
A/Prof. Benjamin Rogers, Monash Health & Monash University
Whilst therapy of AMR infection remains a challenge, we are fortunate to have had a number of new antimicrobial agents come to the market in the past decade. Deployment of ‘new’ antimicrobial entails new challenges, however. This talk will review the challenges of deploying new-to-market therapies for AMR infection.
A/Prof. Sam Forster, Hudson Institute of Medical Research
The human gastrointestinal microbiome is intimately linked to antimicrobial resistance and dissemination. These microbial communities are regularly exposed to orally administered antimicrobials, can harbour antimicrobial genes and can exchange these genes with pathogenic species. In recent work, we have examined and characterised almost 65,000 gene transfer events between 540 commensal species and 12 key pathogens. This work highlights the diversity of mobile genetic elements capable of spreading AMR, the phylogenetic constraints on this gene transfer and identifies and experimentally validates 15 key elements with inter-phyla host range.
Prof. Philip Andrews, Monash University and Victorian Heart Institute
Metals such as silver, copper, mercury and lead have been known from antiquity to act as effective antibacterials. More recent studies have shown that many more metals are capable of behaving as antimicrobials, especially when incorporated in compounds and composite materials. However, they have been largely overlooked in favour of naturally derived or synthetic small molecules or peptides. With the traditional antimicrobial pipeline drying up and a paucity in the diversity of modern antibiotic discovery, perhaps it is time to revisit the power of metals to provide new and effective antimicrobials.
Session 3: Preventing AMR
Dr Rekha Pai Mangalore, Alfred Health
Precision dosing includes adjusting the amount of an antibiotic to the individual needs of each patient, based on characteristics such as age, weight, renal function, liver function, kind of infection, and concurrent drugs. Precision dosage maximises efficacy and safety while minimising toxicity and emergence of resistance. One important tool in precision dosing is therapeutic drug monitoring (TDM), which includes measuring the concentration of the antimicrobial in the blood and adjusting the dose based on the concentrations. This ensures that each patient receives the medicine at the optimal therapeutic concentration, reducing the risk of toxicity and emergence of resistance.
Prof. Dena Lyras, Monash University
One of the biggest barriers to developing new, non-antibiotic strategies for the treatment of enteric infections is that we do not understand well enough how these pathogens function in the gastrointestinal niche, or how these infections impact the host extra-intestinally. This presentation will discuss how fundamental investigations of new disease mechanisms have recalibrated our understanding of enteric infection and disease, and how this new understanding has allowed us to develop effective therapeutic strategies for gut infections that do not involve antibiotics.
A/Prof. Cornelia Landersdorfer, Monash Institute of Pharmaceutical Sciences
Traditionally, an empirical 'one-size-fits-all' approach has been applied to antibiotic dosing. This approach has been increasingly ineffective and may lead to suboptimal antibiotic exposures, risking treatment failure, emergence of resistance and/or toxicity, particularly for compounds with a narrow therapeutic window. Additionally, even at a given daily dose, the shape of the antibiotic exposure profile can substantially influence treatment outcomes. Mathematical models that characterise the population pharmacokinetics and interpatient variability of antibiotics are valuable to predict the dosing regimens required to achieve targeted exposure profiles. Population pharmacokinetic models are ideally suited to be linked with mechanism-based pharmacodynamic models that describe the time-course of bacterial response and are developed based on preclinical studies. Ultimately, such pharmacokinetic/pharmacodynamic models are envisaged to enable model-informed precision dosing for the selection of optimised antibiotic treatment regimens based on the characteristics of the patient and their infecting bacteria.
Session 4: Preventing AMR
CHAIR: Prof. Anton Peleg
Dr Andrew Stewardson, The Alfred & Monash University
A brief overview of challenges that clinical infection prevention services face in preventing AMR colonisation and infection in the clinical setting. This presentation will highlight selected issues relating to prevention, outbreak detection and response where there are gaps in need of novel solutions.
Dr Victor Cadarso, Monash University
Substrate topography at the micro and nanoscale is emerging as a powerful tool to manipulate cell behaviour, but studies into these effects are hampered by a lack of access to topographies that can be readily incorporated with the standard biological techniques and methods of analysis. Current techniques to produce micro and nanopatterned substrates are often difficult to produce across a surface area large enough to perform biological analyses, require time consuming and tricky manipulation of substrates into standard cell culture plates and are typically not made of the same material (polystyrene), which further complicates any comparison with typical cell culture datasets. Furthermore, there are indications that complex topographies with 3D features play a key role in the cell to substrate interactions, but obtaining such features over large areas is still extremely challenging.
We have developed simple and scalable technologies to overcome these drawbacks. Here I will show how these technologies can be used to implement topographies on standard Tissue Culture Plastics, regularly used by biologists and how complex 3D topographies can be formed by means of a single standard UV-lithography exposure. We prove the effect of these by testing these two technologies on mammal and bacterial cells, for cell regulation and fate determination and for antimicrobial purposes. These technologies could open up the potential of micro/nano-topographies in the culture and screening across an enormous range of biological applications.
A/Prof. Mark Davis, Monash University
Mark's presentation will discuss AMR prevention for individuals and communities that integrate regulatory, health systems, prescriber and consumer educational aims and methods. Mark will also reflect on the impact of the COVID pandemic on public engagements with microbial threats to life and implications for AMR prevention.