Advancing Sepsis and AMR Diagnostics

Highlights from the British Society for Microbial Technology Conference

In May, I attended the British Society for Microbial Technology (BSMT) Conference in London to explore innovations in sepsis diagnostics, antimicrobial resistance (AMR) monitoring, and metagenomic sequencing. It was amazing to walk through the RAF museum on my way to register. It was the conference’s 40th anniversary, and for as long as the society has been going, sepsis and antimicrobial resistance have been a high priority through the years. 

This conference allowed me to get a better insight into the market of microbiology technologies and what incredible work is going on within the microbiology sector. This conference connects the medical, clinical, technical, commercial and academic fields, and it is something that VH Bio & our product partners, Molzym, PSS & EKF/Longhorn with Primestore, would fit well into. 

In this blog, I will share some of the information I learnt from the speakers and also how our product partners could influence each sector. 

How New Technologies Are Transforming Sepsis Diagnostics and Antibiotic Stewardship 

Sepsis is a serious condition resulting from the presence of harmful microorganisms in the blood or other tissues and the body’s response to their presence. This can potentially lead to the malfunctioning of various organs, shock & death. According to the UK Sepsis Trust, 37,000 people are estimated to die from sepsis each year, with hospitalisation for sepsis having more than doubled over the last 10 years (Parliamentary and Health Service Ombudsman, 2013). This talk focused on 4 main points: antimicrobial stewardship, source control and infection prevention, infection biomarkers and the further work needed, such as meta-analyses and the implementation of this in routine care.

Key points I took from this talk are: 

• Studies are showing how to better administer antibiotics, focusing on the drug type, dose and duration, as well as when to review which antibiotics are helping shape new guidance. 

• Ongoing clinical trials are showing the potential of infection biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) to hold diagnostic value to help assess when antibiotic duration can be reduced. 

• Studies like these contribute to optimising treatment packages, enhancing patient outcomes while improving cost-effectiveness. 

It was interesting to hear this topic from a broad clinical perspective and hear how these interventions and improvements in guidance from studies can help patients firsthand.  

How can Molzym help? 

Care failings in the first few hours are where rapid diagnosis and simple treatment can be critical. Molzym can help here, as one of the company’s goals is to address technological gaps faced daily by clinical laboratories. This can be achieved by using the manual Sepsi-test kit or the automated SelectNA plus instrument with either the SNplus or MicroDx kit (Table 1). These kits allow the user to deplete the host DNA presence in their clinical samples and extract the microbial content to then assess downstream. Metagenomic sequencing downstream is also making its way into the clinical space, and Molzym have recently released a technical note, where they have used the automated platform and targeted 16S amplicon Oxford Nanopore sequencing downstream, which you can see HERE. 

Table 1: The CE-IVD kits available from Molzym. The automated SelectNA plus platform compatible kits, plus the manual Sepsi-test kit and what they can do for customers. Bold: CE-IVD portions of the workflow *Sanger sequencing reagents will need to be purchased separately, or samples sent to a provider with the provided primers. 

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Combating Antimicrobial Resistance (AMR) with Molecular Diagnostics 

Antibiotics have been described as magic bullets. Since the first antibiotic discovery, penicillin in 1928, antibiotic discovery has transitioned from initial discoveries and mass production to the current challenge of antibiotic resistance. In 2014, the World Health Organisation (WHO) released a report warning that the world was moving closer to a post-antibiotic era, which would result in common infections becoming untreatable due to AMR (WHO, 2014).  By 2050, it is predicted that there will be around 10 million deaths globally because of AMR. 

The next talk highlighted the importance of anti-microbial resistance and some of the technologies used within their laboratory for studies into how we can reduce the burden of AMR in the future. One of the studies that was discussed in this talk was from a published paper by Cave et al, (2019), which investigates the molecular characteristics in multidrug-resistant staphylococci. This pathogen can spread through skin-to-skin and skin-surface contact, and the study compared staphylococci isolates recovered from high-frequency touched surfaces in public areas in the community and hospitals. Of isolates found at high-frequency hand touch surfaces, 34.9% were multidrug-resistant, and of isolates found from different public areas within a hospital setting, 46.4% were multidrug-resistant. This study highlighted important reservoirs for multidrug-resistant staphylococci by whole-genome metagenomic sequencing. 

How can Molzym help? 

This talk also included another study which looked at low biomass air microbiomes for public health pathogens & AMR surveillance using mNGS, which is yet to be published. The depletion of host DNA is important in a range of low-biomass samples to prevent the overwhelming host DNA results during sequencing. Molzym can help with AMR studies when it comes to metagenomic sequencing by allowing the identification of AMR genes within your sample. This can be seen in the paper HERE. 

Another important DNA detection method is PCR. The use of PCR reagents, which are contaminant-free and can detect down to the femtogram level, can also be purchased from Molzym in the formats in Table 2. 

Table 2: The different PCR assays from Molzym and the kits available. 

Accessible clinical microbiology 

The next speaker talked about the development and deployment of mini microbiology laboratories. These laboratories allow methods such as blood cultures and urines to be performed by non-expert microbiologists and consist of modular components which contain equipment, reagents and consumables, documents and training resources, IT/data management, lab benches and incubators. The results of these mini-laboratories were presented at ECCMID in 2023 and have been shown to be a useful tool for microbiology at a district level in various countries. These mini laboratories are designed for diagnostics at a district level and not as a full clinical or mobile laboratory for outbreak investigations. 

How can Primestore MTM help? 

PrimeStore MTM, provided by EKF and Longhorn, is an inactivation medium which effectively inactivates and kills viral and bacterial pathogens whilst preserving and stabilising RNA and DNA. This reduces the safety risks of handling pathogenic samples and allows collection, inactivation, shipping and storage in a single tube, which can be used in settings where cold chain transport and storage are not possible. Compared to other transport media, PrimeStore maintains sample integrity, doesn’t inhibit downstream PCR reactions and has a longer shelf life. 

Mobile laboratories for rapid support in global outbreaks 

The next talk was about developing the UK public health rapid support team’s mobile lab as a tool for global outbreak response. This team is deployed during times of developing outbreaks of pathogens, and example being the Ebola outbreak in the 2010s. The equipment deployed is a modular system which can be transported by van or car and includes a biosafety glove box, PCR hood and compact analysers which would allow the assessment of around 50 samples per day by 4 team members. The use of these laboratories is a joint program between the UKHSA & LSTM and is an outbreak response deployed agreed by WHO/GOARN or the country where the outbreak is happening. 

How can PSS and their instrumentation help? 

PSS manufactures nucleic acid extraction instruments: the MagLEAD 12gC Link and the GeneLEAD VIII. The MagLEAD 12gC Link is a user-friendly, closed system instrument for the extraction of nucleic acids using built-in protocols covering various sample types such as blood and sputum.  The fully automated system ensures quick and easy set-up with prefilled reagents and less than 5 minutes of hands-on time. The GeneLEAD VIII allows you to perform additional lyophilised PCR assays along with nucleic extraction, giving you a sample-to-result protocol which is customisable for each lane and utilises six channels and eight independently controlled thermal cyclers. With a HEPA filter and a UV decontamination lamp, the GeneLEAD VIII is built with the modern laboratory in mind. The current PCR assays include SARS-CoV-2, respiratory viruses, MRSA, monkey pox and more! The lyophilised format of these assays allows easier transportation and storage appropriate for mobile laboratories. 

Epidemiological surveillance in wastewater 

The next talk highlighted the importance of water sampling for epidemiological surveillance. This type of method is used to survey the potential presence of diseases such as Polio and is vital in the prevention of outbreaks. Some diseases, such as flu, are not as visible in wastewater as the viral load is not as high. It was interesting to see how researchers can use the wastewater and locations to identify possible exposure routes. The use of genomic methods is aiding this area of research, too. 

Wastewater currently isn’t a valid sample type for the MolYsis kits and is not appropriate for the automated system. One reason for this is the high volumes of wastewater which may be needed for particular research questions. The MolYsis kits can be used for a maximum of 5 mL. 

Latest Advances in Fungal Infection Detection and Diagnostics 

The final talk was about the advances in the diagnosis of invasive and systemic fungal infections. The speaker talked about the current methods, such as 18S broad-range PCR and culture-based methods. There is, however a resistance problem in mycology, despite fungal DNA being less prone to mutation compared to bacterial DNA. Fatality is an increasing global burden because of fungal infections, with most cases in intensive care units, from gastrointestinal trauma or surgery and in patients who have had organ transplants due to having a suppressed immune system. Diagnostic tools for different fungal types include PCR and microscopy tests, but these tests can have varying sensitivity, specificity and predictive values, which can also be dependent on sample type. One single test which can diagnose within the clinic does not currently exist.  

How can Molzym help? 

Fungal DNA can be removed unintentionally as a result of host DNA depletion kits, but the host DNA depletion kits from Molzym have been shown to extract fungal DNA, such as Aspergillus and Candida. This can be seen on the list of microorganisms extracted from a variety of samples. Click HERE to view the full list of extracted microorganisms. 

From this conference, it was highlighted that there are multiple approaches to combat the health burden of AMR, spanning over research, clinical and public sectors. These approaches include infection prevention and control, public engagement and education, vaccination, optimising antibiotic use, the development of new treatments and diagnostics, surveillance and monitoring, and international collaboration. One common theme within the scientific field, however, is metagenomic sequencing, which is stepping into the spotlight as a major advancement. 

To discover how VH Bio’s innovative solutions, including rapid sepsis diagnostics, advanced PCR assays for antimicrobial resistance research, and safe sample transport with PrimeStore MTM, can enhance your microbiology workflows, contact our team today or explore our complete product catalogue to learn more. 

Reference 

Cave, R., Misra, R., Chen, J., Wang, S., Mkrtchyan, H. (2019) Whole genome sequencing revealed new molecular characteristics in multidrug resistant staphylococci recovered from high frequency touched surfaces in London. Scientific Reports. 9(1) doi: 10.1038/s41598-019-45886-6. 

Parliamentary and Health Service Ombudsman. (2013) Time to Act: Severe sepsis: rapid diagnosis and treatment saves lives. https://www.ombudsman.org.uk/sites/default/files/2016-08/FINAL_Sepsis_Report_web.pdf 

World Health Organization (2014) Antimicrobial resistance: global report on surveillance. https://iris.who.int/bitstream/handle/10665/112642/9789241564748_eng.pdf?sequence=1