Combatting AMR: advanced diagnostics and resistance profiling for H.pylori

The bacterium Helicobacter pylori is a key contributor to antimicrobial resistance. Here, Mast Group examines the advantages offered by novel molecular diagnostics over current options, including improvements in antimicrobial stewardship.

Antimicrobial resistance (AMR) continues to pose a significant global health challenge, affecting treatment outcomes for a wide range of infections. In 2024, the UK government released Confronting antimicrobial resistance 2024 to 2029, the second iteration of its five-year AMR action plan, aiming to reduce the AMR burden by improving antibiotic stewardship, enhancing infection prevention measures, and driving innovation in diagnostics and treatments. Key goals include achieving a 15% reduction inappropriate antibiotic prescriptions, emphasising the need to improve diagnostic precision and reduce reliance on broad-spectrum antibiotics.¹ While these goals are ambitious, the government has allocated significant funding to support their achievement with over £200 million earmarked for AMR-related initiatives, including the development of diagnostic tools and stewardship programmes.2

One of the main focuses of the plan is the 'development and implementation of diagnostics that enable the targeted use of antimicrobials and reduce unnecessary prescribing'. This highlights the crucial role that diagnostics play in ensuring effective antibiotic use and mitigating resistance. This shift from empiric prescribing to evidence-based precision medicine, strongly advocated by the AMR action plan, plays a pivotal role in enabling better treatment outcomes and curbing the rise of resistant strains through the provision of timely, accurate and actionable diagnostic data. Among the pathogens contributing to the AMR crisis is Helicobacter pylori, a bacterium associated with serious gastric conditions, such as gastric cancer. Addressing H. pylori resistance, particularly to clarithromycin, requires advanced diagnostic solutions to ensure effective and targeted treatments. 

H. pylori is a spiral-shaped, Gram-negative bacterium that colonises the gastric mucosa. Whilst not commensal, it is believed to infect roughly half of the world's population.3 It is transmitted primarily via the oral-oral or faecal-oral route, with poor sanitation and overcrowding being significant risk factors for transmission.4 Once established in the stomach lining, H. pylori can persist for decades due to its ability to evade the immune response and adapt to the acidic gastric environment through mechanisms such as urease production which neutralises stomach acid by converting ammonia to bicarbonate, increasing the local pH.⁵

Pathogenesis of H. pylori involves a range of virulence factors that enable it to adhere to the gastric epithelium, evade host defences, and cause tissue damage. Key virulence factors include the cytotoxin-associated gene A (cagA) and vacuolating cytotoxin A (vacA), both of which contribute to inflammation and cellular damage. Chronic infection results in persistent inflammation, which can exacerbate tissue damage over time, contributing to gastritis, peptic ulcers, and, in some cases, gastric cancer. In fact, CagA, a protein injected into the host epithelial cells, was the first bacterial protein found to be directly involved in oncogenesis. The bacterium is classified as a Group 1 carcinogen by the World Health Organization due to its strong association with gastric malignancies.⁶ 

Current treatment guidelines in the UK, whilst based on local resistance data, generally recommended a first-line triple therapy consisting of a proton pump inhibitor (PPI), clarithromycin, and either amoxicillin or metronidazole for 7-14 days. However, the rising prevalence of clarithromycin resistance is significantly impacting the efficacy of this regimen, with treatment success rates falling below 80% in some cases. ⁷ This has led to the recommendation of alternative regimens, such as quadruple therapy (adding bismuth or a second antibiotic) in areas with high resistance rates or in cases of treatment failure.

The reliance on empiric prescribing for  H. pylori infections presents significant challenges. Empiric treatment generally assumes susceptibility to clarithromycin, which may not reflect the actual resistance profile of the infection. This approach increases the likelihood of treatment failure, necessitating repeat courses of antibiotics and exposing patients to prolonged symptoms and potential complications. Furthermore, ineffective treatments contribute to the broader issue of AMR by promoting the selection of resistant strains. Recent UK studies estimate that clarithromycin resistance in  H. pylori exceeds 20% with some reports indicating rates over 70%. ^8,9 These findings highlight the urgent need for diagnostics that guide therapy based on resistance profiles rather than assumptions.

In the UK, the diagnosis of  H. pylori  and assessment of antibiotic resistance relies on several established methods. These include:

• Urea breath test (UBT): a non-invasive test that detects  H. pylori infection by measuring labelled carbon dioxide in the patient's breath after ingestion of a urea solution. While highly sensitive for detecting active infection, it does not provide information about antibiotic resistance.

• Stool antigen test: a cost-effective and non-invasive method that detects  H. pylori antigens in stool samples. Like the UBT, it confirms infection but lacks the ability to identify resistance patterns.

• Endoscopy with biopsy: the gold standard for diagnosing  H. pylori involving histopathology, culture, and susceptibility testing. This method allows for direct observation of the gastric mucosa and resistance profiling through culture. However, it is invasive. labour intensive, and has a longer turnaround time.

• Serology: used to detect antibodies against  H. pylori. While useful in certain contexts it cannot distinguish between active and past infections, nor does it provide resistance data.

These current approaches do have a number of limitations and disadvantages which should be taken into account. Most non-invasive methods (UBT, stool antigen) do not offer insights into resistance, making them inadequate for guiding tailored treatments, while culture and susceptibility testing, though comprehensive, are slow and resource intensive. The current reliance on empiric therapy - due to diagnostic limitations - contributes to resistance development, as ineffective antibiotics may be prescribed. 

These limitations highlight the need for advanced molecular diagnostics that combine infection detection with resistance profiling in a single, streamlined test.

Molecular diagnostics (MDx) offer a solution to these challenges by providing rapid and accurate detection of active infection and resistance markers. MDx can deliver results in hours, enabling timely and informed treatment decisions.

Key benefits of MDx include:

• High sensitivity and specificity: molecular tests are more sensitive and specific than classical methods due to their ability to amplify and detect even small amounts of bacterial DNA, ensuring accurate results even in low bacterial load scenarios.

• Comprehensive information: molecular diagnostics provide not only detection of active infection but also resistance profiling in  a single, streamlined process, offering clinicians critical data to guide targeted treatments. 

• Reduced turnaround times: MDx significantly shortens diagnostic time compared to most classical methods, often providing results within hours instead of days. This allows clinicians to initiate appropriate therapy more quickly, reducing patient wait times and potentially improving clinical outcomes. 

• Labour savings: automated platforms streamline testing, minimising manual effort and reducing the risk of errors. This can enhance overall operational efficiency.

• Broader healthcare savings: by reducing the need for repeat visits and failed treatments, molecular diagnostics help free valuable bed space, lower overall healthcare costs, and improve resource allocation within the healthcare system.

By incorporating MDx into routine diagnostics, healthcare providers can not only improve patient outcomes but also transform antimicrobial stewardship by reducing resistance spread and optimising treatment efficiency.¹⁰ 

Seegene's H. pylori & ClariR panel represents a significant advancement in the molecular detection of H. pylori and its resistance markers. The panel is designed to simultaneously detect H. pylori infection and mutations in the 23S rRNA gene that confer clarithromycin resistance. Key features include:

• Comprehensive targeting: the panel identifies three distinct mutations associated with clarithromycin resistance (A2142G, A2142C, and  A2143G), ensuring robust coverage of clinically relevant resistance mechanisms.

• Efficiency and speed: results are available within hours (~4-hour TAT), supporting faster clinical decision-making compared to traditional culture methods, which can take days.

• Broad sample type compatibility: the Seegene panel is validated for use both with stool and gastric biopsy samples, providing clinicians with the flexibility to choose a non-invasive testing option.

• Workflow integration: the assay is compatible with automated platforms, such as Seegene's STARlet, NIMBUS, AIOS and CFX96, streamlining the diagnostic process.

• Universal assay compatibility: all Seegene molecular assays are compatible with these automated platforms, allowing laboratories to efficiently process a wide range of diagnostic tests on a single system and expand their testing repertoire.

Clinical validation studies have demonstrated the panel's high sensitivity and specificity, with some studies showing detection sensitivity and specificity rates of 100%, and up to 100% sensitivity and specificity for the resistance mutations. ^11,12 

This makes it a highly reliable tool for managing H. pylori underscores the urgent need for advanced diagnostics in clinical practice. Seegene's H. pylori & ClariR panel aligns with the UK's AMR action plan by facilitating targeted treatments and supporting antibiotic stewardship. Integrating molecular diagnostics into routine workflows not only improves patient outcomes but also strengthens efforts to combat antimicrobial resistance on a broader scale.

As the healthcare community continues to confront the AMR crisis, adopting innovative diagnostic solutions like Seegene's panel is essential. By enabling precise, timely detection of resistance, we can take a proactive step toward preserving the efficacy of antibiotics and ensuring better care for patients with  H. pylori infections.