MHRA and NHS enhance bacterial infection diagnosis with DNA sequencing

The Innovation Platform spoke with Saba Anwar, Senior Scientist at the Medicines and Healthcare products Regulatory Agency (MHRA), about a pilot study with Barts Health National Health Service (NHS) Trust that reduced bacterial infection diagnosis time using DNA sequencing technology

A recent collaboration between the MHRA and the NHS represents a significant advancement in the UK’s management of infectious diseases. Utilising innovative DNA sequencing technology, they have reduced the diagnosis time for bacterial infections from weeks to just 48 hours. This rapid diagnostic capability enhances clinical assessments and enables quicker initiation of optimal antimicrobial therapy. Through a pilot study, the MHRA supported Barts Health NHS Trust by providing a highly characterised reference material established by the WHO as International Reference Reagents. Using them, Barts Health NHS Trust demonstrated the technology’s potential and suitability for widespread adoption across the NHS underpinned by these reference reagents. This will help address the urgent issue of antimicrobial resistance, which contributes to about one million deaths globally each year.

The Innovation Platform spoke with Saba Anwar, Senior Scientist, Research & Development at the MHRA, about the technology, pilot study findings, and the pathway toward standardisation of DNA sequencing diagnostic technologies within the NHS, showcasing their potential impact on the future of clinical diagnostics.

Can you provide a brief overview of the DNA sequencing diagnostic technology developed by the collaboration and the study conducted with Barts Health NHS Trust? What impacts did the pilot study find?

A major challenge for clinical management of patients already receiving antibiotic treatment is ongoing monitoring of bacteria present in ‘culture-negative’ samples. Barts NHS Health Trust wished to introduce a diagnostic service to analyse these culture-negative samples. The goal was to apply Oxford Nanopore technology to characterise 16S RNA gene sequences and so detect and identify the bacterial pathogen unequivocally. Moreover, the method had the potential to be run rapidly and directly in a hospital lab, allowing for near-patient, real-time diagnostics.

A pilot study was undertaken at Barts Health NHS Trust and involved close collaboration with scientists at the National Measurement Laboratory at the Laboratory of the Government Chemist (LGC-NML) and my team at the Science Campus of the Medicines and Healthcare products Regulatory Agency. We developed WHO Gut Microbiome DNA and Whole-cell reference reagents, which were used to validate every step of the sequencing workflow, enabling faster and more accurate diagnoses for severe infections, enabling clinicians to tailor antibiotic treatment earlier and replace broad-spectrum antibiotics with more effective treatments. It also identified pathogens in culture-negative cases that would otherwise have remained undetected: vital clinical information that guided more effective clinical care.

The study demonstrated that nanopore sequencing developed by Barts with support from MHRA and LGC-NML can be successfully established and embedded within NHS hospital laboratories, allowing for broad adoption across the NHS.

In your experience, through this study and previous case studies, what are the key advantages of DNA technology compared to traditional diagnostic methods?

Direct DNA sequencing offers several advantages over traditional/existing diagnostic tests, in terms of speed, precision, and its ability to detect pathogens that conventional culture-based approaches often miss. Sequencing can return results within 48 hours compared with the seven days typically required to identify a bacterial infection by culture, or the many weeks needed for slow-growing organisms. The rapid turnaround of results is crucial for life-threatening conditions such as sepsis or meningitis, when early, accurate treatment can be lifesaving.

Sequencing identifies pathogens with greater precision, allowing clinicians to optimise treatment plans more quickly, reducing the use of broad-spectrum antibiotics, leading to better antimicrobial stewardship. Importantly, diagnostic methods based on direct sequencing can still provide a diagnosis when clinical samples cannot be cultured because of prior antibiotic treatment, low bacterial numbers, or slow-growing organisms.

The laboratories at the MHRA Science Campus do not undertake clinical diagnostics. One of our roles is to develop robust physical standards that assure complex diagnostics, such as sequencing, and promote their adoption and use to support complex clinical diagnostics, such as DNA sequencing, by clinical laboratories such as the NHS.

Could you discuss the steps the MHRA is taking towards standardising DNA sequencing technologies within the NHS? Since the release of the study, what progress has been made towards this?

The current work at the MHRA Science Campus builds on a 100-year history of developing physical standards and reference materials that harmonise measurement of complex assays.  With regards to clinical diagnostics, we work closely with multiple stakeholders, including the NHS, to ensure that tests that rely on new technologies, such as the direct sequencing of amplified nucleic acid, provide results that are reproducible, comparable, and accurate. We achieve this by applying the principles of biological standardisation, first developed by Sir Henry Dale 100 years ago.  This involves the preparation of extremely well-characterised materials that need to be co-processed along with clinical samples.  By comparison with these reference materials, the performance of each run of the assay can be established, and the quality and quantity of the resulting data can be assessed.  These materials contribute to the standardisation of technologies such as the new methods of sequencing applied at Barts NHS Trust, without being prescriptive about the method. By incorporating data generated across multiple laboratories, we can determine which approach is most suitable to ensure reproducibility, comparability, and ultimately reliable clinical outcomes based on decisions informed by the data. The use of these standards ultimately supports better clinical outcomes for patients.

What challenges do you anticipate in this process, and what timeline do you foresee for its implementation across more hospitals?

One of the main challenges is the current variability seen in Next Generation Sequencing (NGS) results between different laboratories. Without a consistent framework, differences in sample preparation, sequencing platforms, bioinformatic pipelines, and interpretation criteria can all lead to inconsistent outputs. To address this, appropriate standards are essential. Applying robust, widely adopted standards will allow results to be compared reliably across sites, which is crucial if sequencing-based diagnostics are to be implemented safely and confidently within the NHS. Establishing and applying the right standards is the key step that will enable wider implementation across the NHS.

The technology is also promising for tackling AMR. Can you summarise how DNA sequencing technologies can help combat antimicrobial resistance and prevent hospital outbreaks? Following the November 2024 pilot study on this topic, what progress has been made towards implementing and regulating this technology for AMR applications?

Direct DNA sequencing is rapidly becoming a critical tool in the fight against antimicrobial resistance.  It offers a level of speed and acuity in data that existing culture-based methods cannot match. The analysis of bacterial DNA amplified directly from a patient sample enables the precise identification of the organism causing an infection, how this organism is genetically related to those recovered from other patients exhibiting the same symptoms, and can establish whether the organism carries genes that increase resistance against potential drugs (AMR genes). All these pieces of information allow clinicians to select the most appropriate treatment more quickly and avoid the broad-spectrum antibiotics that drive resistance. This not only protects patients from avoidable side effects but also contributes to better long-term clinical outcomes by slowing the development of resistance.

Defining AMR genes present in bacteria detected provides clinical value even when bacteria are present in low numbers or are difficult to culture, since sequencing can identify resistance markers that guide more precise therapy. This provides clinicians with actionable information and ensures patients receive the most effective care.

Sequencing also provides hospitals with a powerful surveillance tool. By comparing AMR genes from different patients, teams can identify transmission pathways and intervene early to control hospital outbreaks.

To support and strengthen efforts against AMR, the MHRA science campus is developing candidate reference reagents for AMR gene detection. These reagents are intended to establish the accuracy of AMR gene detection tools, define the resistome within samples, and harmonise DNA sequencing methods and analytical pipelines.

Please note, this article will also appear in the 26th edition of our quarterly publication.