MICROBIAL TECHNOLOGY
microbiology laboratory from scratch in a rural hospital. Next, Dr Moore discussed the opportunities for rapid diagnostic tests (RDTs) at different stages of the patient care pathway. These could be considered in three distinct test areas. In the initiation stage of the patient care pathway, say the first four to six hours, RDTs could be described as essential at this stage to determine whether an antimicrobial is required and, if an antimicrobial is appropriate, to determine whether it should be antibacterial or antiviral. Examples of these RDTs could be a PCT test or rapid influenza test. Second, on- treatment stage, here an RDT might be considered desirable but not essential. It might be used to facilitate targeting or broadening of therapy; for example, molecular testing and drug resistance testing (CRE, respiratory or GI infection testing) and a PCT test to inform patient prognosis. Last, in the de-escalation/ cessation stage, an RDT again might be desirable but probably not essential. The results of an RDT might facilitate an early intravenous (iv) to oral switch and the de- escalation or cessation of antimicrobials. So, for example, the results of a MALDI- TOF or liquid culture test or lateral flow assay might lead to de-escalation, and a falling PCT might lead to cessation of antimicrobial treatment altogether. Finally, Dr Moore described what he called the ‘5P value framework’ supporting optimised antimicrobial decision-making. He admitted it took a bit of effort and a lot of coffee to come up with five words or phrases to describe the process beginning with P, but they managed it and it does provide a useful framework to consider how we should value rapid diagnostics. These are summarised as follows: n Programme support: Enable specific antimicrobial stewardship programme (ASP) interventions and provision of metadata for delineating ASP outcome KPIs.
n Preserve: Quantifiable changes in antimicrobial consumption, appropriateness of antimicrobial prescriptions, and potential antimicrobial resistance.
n Practicable: Impact on laboratory and
clinical area sample flow (including logistics, information technology, and personnel) and patient flow (including admission avoidance, and length of stay) across LMIC and HIC settings.
n Population health: Quantifiable impact on population health through both impact on infection transmission and speed of return to work.
n Precision: Evaluable test performance characteristics which may supersede existing traditional laboratory ‘gold standard’ diagnostics.
It is well worth reading a recent paper by Dr Moore and colleagues2
where these topics are discussed in more detail.
Molecular diagnostics: the next generation Our next speaker had a hard act to follow. Dr Jesus Rodriguez-Manzano (Senior Lecturer in Diagnostics for Infectious Diseases at Imperial College, London, and Deputy Director of the Centre for Antimicrobial Optimisation [CAMO]) provided insight into the next generation of molecular diagnostics, and explained how digital technologies can be leveraged to enhance multiplexing in real-time PCR.
Dr Rodriguez-Manzano and his team
are researching diagnostic solutions that address the challenges of diagnosing diseases in resource-limited settings. In response to the statistic that 47% of the global population has little to no access to diagnostics,3
ProtonDx has
developed three innovative devices, the SmartLid, Dragonfly and Lacewing, which are sample-to-result molecular-based diagnostics that support decentralised healthcare testing. The ProtonDx ‘lab-in-a- bag’ concept literally includes everything you need to use the test (pipette, tips, Dragonfly device) in a regular-sized backpack. Impressive!
In addition to decentralised testing solutions, there is a need to improve multiplexing capabilities of existing quantitative PCR (qPCR) platforms and chemistries to increase the throughput of diagnostic laboratories without hardware modification. Detection of multiple targets in a single test, such as multiple respiratory pathogens, reduces
In addition to decentralised testing solutions, there is a need to improve multiplexing capabilities of existing quantitative PCR (qPCR) platforms and chemistries to increase the throughput of diagnostic laboratories without hardware modification
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the amount of reagents required (and therefore the cost of the test) and maximises the use of precious clinical samples.
The team at Imperial has developed a unique data-driven solution to enhance multiplexing capabilities for real-time PCR platforms. Dr Rodriguez- Manzano described the technology behind data-driven multiplexing, such as multidimensional standard curves where each data point has its own unique pattern that are highly correlated. Additionally, instead of using single features, with the application of AI, amplification curve analysis can be combined with melting curve analysis to enhance detection of multiple targets. These innovative technologies have been validated with clinical isolates and Dr Rodriguez-Manzano shared examples of detection and differentiation of carbapenemase-producing Enterobacterales and 7-plex respiratory pathogens in a single well. The long-term vision of this work is to maintain the traditional qPCR workflow and instrumentation while streamlining data analysis and management. Dr Rodriguez-Manzano succinctly described how digital technologies can complement existing single-well and spatial multiplexing solutions and how innovative rule-based and data-driven software solutions can help rationalise and optimise multiplex PCR design. PCR has certainly come a long way since its discovery in 1983!
Rural microbiology in India By way of complete contrast to the first two talks, the final presentation of the morning session was by Ivor Mitchelmore, former Chief Biomedical Scientist, Luton and Dunstable Hospital, who described the problems he had encountered in setting up a Microbiology Service in a hospital attached to a rural hospital in India. The Khristiya Seva Niketan (KSN) Hospital in West Bengal, India, is set in a rural location, around four to five hours’ drive from Kolkata (Fig 1), and was built in 1914. KSN hospital (Fig 2) is a not-for-profit organisation that provides essential primary and secondary healthcare to rural tribal communities. Ivor visited the hospital in 2012 to celebrate its Centenary, and it was at that point he saw the opportunity to help set up a microbiology laboratory.
The hospital consisted of two wards (Male and Female), a maternity ward and children’s ward. An operating theatre and pharmacy were located in separate buildings. They had a haematology laboratory, where they were routinely offering blood tests, where Ivor helped
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