Interim guidance for the management of Helicobacter pylori cases

Who this guidance is for

This guidance is for gastroenterologists and medical microbiologists to use during the pause to the Helicobacter pylori (H. pylori) reference service from the UKHSA Gastrointestinal Bacteria Reference Unit (GBRU).

Background

At present, gastric biopsies are recommended for H. pylori culture and antimicrobial susceptibility testing (AST) for patients with dyspepsia who meet any of the following criteria [1,2]:

• failed at least first- and second-line treatments
• have limited options due to drug hypersensitivity
• live in an area with high resistance rates.

H. pylori service from the reference laboratory Gastrointestinal Bacteria Reference Unit (GBRU) (currently paused)

The UKHSA GBRU undertakes culture for H. pylori at 35 to 38°C under microaerophilic conditions for up to 10 days. H. pylori typically produce small, uniformly sized, translucent to greyish colonies on Columbia blood agar (10%) and H. pylori selective media. Identification is confirmed by Gram-staining (appear as Gram-negative, curved-shaped bacteria), catalase, oxidase and urease reactions [3,4]. H. pylori-positive cultures are tested for phenotypic susceptibility to clarithromycin, metronidazole, amoxicillin, tetracycline, and levofloxacin using E-tests (bioMérieux). Antimicrobial susceptibilities are interpreted using specific breakpoints for H. pylori in EUCAST (v 15.0) [5].

As of 6 January 2025, the H. pylori service from the GBRU is paused.

Management of patients with H. pylori during pause in service provision

1. Local phenotypic AST testing

During the pause to the H. pylori service, your local microbiology laboratory may be able to establish this service locally. Alternatively, this can be set up using the method outlined above. Commercial stool H. pylori antigen tests which detect clarithromycin resistance are also available. Please contact GBRU if you require advice in setting up your own service GBRU@ukhsa.gov.uk.

2. Empiric antimicrobial treatment for patients with H. pylori who have failed at least first-and second-line antimicrobial courses

In the absence of gastric biopsy AST testing, empirical antimicrobial options for third-line treatment are challenging. Various options are proposed by the Maastricht VI /Florence and Toronto Consensus Reports and American College of Gastroenterology [6,7,8]. The choice of what treatment regimen to use on treatment-experienced patients will be specific for each patient and depend on several factors, including previous combination of antimicrobials trialled and whether the patient has any allergies.

Secondary phenotypic resistance data sent to GBRU over a 10-year period revealed low incidences of amoxicillin (2%) and tetracycline (less than 1%) resistance, in contrast to higher rates of resistance to clarithromycin (76%) and metronidazole (87%) [9]. In addition, phenotypic resistance to levofloxacin increased over the 10 years, from 16% to 27%. Therefore, consider eradication regimens with combinations of amoxicillin and tetracycline with bismuth for refractory H. pylori infections [6].  If bismuth is not available, high-dose proton pump inhibitor (PPI)-amoxicillin dual or a rifabutin-containing regimen could be considered [6].

Generally, treatment for 14 days is recommended for these treatment-experienced patients, however, the optimal length of treatment is debatable, with some evidence that 10 days of treatment may be adequate to clear infection [6,7, 8]. Furthermore, it is crucial to emphasise the importance of compliance and sufficient gastric acid suppression for successful eradication.

3. Antimicrobial treatment for patients with AST results from previous gastric biopsies

For those patients with AST results from previous gastric biopsies, it is suggested that these previous results may be used to guide the choice of antimicrobials. GBRU phenotypic antibiotic susceptibility data of H. pylori isolates from sequential gastric biopsies over a 10-year period showed minimal change in antibiotic susceptibility patterns, with only approximately 30% of biopsied patients showing a change in susceptibility in one or more antimicrobial agent between their samples [9].

4. Use of bismuth

Pylera is a 3-in-1 combination pill of 140 mg bismuth subcitrate potassium, 125 mg metronidazole, and 125 mg tetracycline hydrochloride. It is approved by the Medicines and Healthcare products Regulatory Agency (MHRA), and available in the UK [10]. A quadruple regimen with a PPI (for example omeprazole) for 10 days is recommended for refractory / difficult-to-treat cases and compliance is far better due to the lower pill burden, with success rates of above 90% described in the literature in clinical practice [11].

Bismuth subcitrate can be imported from Spain and prescribed on named-patient basis.

Useful contacts

Clinical advice:  Medical Microbiologist at the Gastrointestinal Infections Food Safety One Health (GIFSOH), Colindale at GBRU@ukhsa.gov.uk or call the Colindale Duty Doctor Service on 0208 200 4400

Laboratory advice: Contact the team at Gastrointestinal Bacteriology Reference Unit (GBRU), Colindale at  GBRU@ukhsa.gov.uk

Contributors

Dr Vanessa Wong, Consultant in Medical Microbiology and Infectious Diseases, Gastrointestinal Infections & Food Safety (One Health) Division, UKHSA, Colindale, London

Dr Gauri Godbole, Consultant in Medical Microbiology and Parasitology, Gastrointestinal Infections & Food Safety (One Health) Division, UKHSA, Colindale, London

Dr Craig Swift, Head of Helicobacter pylori service, Gastrointestinal Bacteria Reference Unit (GBRU), UKHSA, Colindale, London

References

1. British Infection Association and Public Health England’s Test and treat for Helicobacter pylori in dyspepsia. London; 2004, latest review 2017, updated 2019
2. NICE Guidance: Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. Clinical guideline [CG184] Published: 03 September 2014 Last updated: 18 October 2019
3. Marc R. Couturier, 2023. Helicobacter, In: Carroll KC, Pfaller MA Manual of Clinical Microbiology, 13th Edition. ASM Press, Washington, DC
4. Owen, R. J., S. R. Martin, and P. Borman. Rapid Urea hydrolysis by gastric Campylobacters The Lancet 1985;325;8420:111
5. The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretations of MICs and zone diameters. Version 15.0, 2025. Last accessed 15/01/2025
6. Malfertheiner P, Megraud F, Rokkas T On behalf of the European Helicobacter and Microbiota Study group, and others. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report Gut 2022;71:1724-1762 doi: 10.1136/gutjnl-2022-327745. doi: 10.1136/gutjnl-2022-327745
7. Fallone CA, Chiba N, Veldbuyzen van Zanten S and others. The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults Gastroenterology 2016;151:51–69
8. Chey WD, Leontiadis GL, Howden CW, and others. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection The American Journal of Gastroenterology 2017;119: 1730-1753. 1. DOI: 10.14309/ajg.0000000000002968
9. Wong V, Hayden I, Swift C, and others. Antimicrobial resistance in Helicobacter pylori – a 10-year perspective from the National Gastrointestinal Bacteria Reference Unit, UK Health Security Agency, United Kingdom Abstract ID 04369 Presented at 27 to 30 April 2024 ECCMID (34th European Congress of Clinical Microbiology and Infectious Diseases), Barcelona, Spain
10. Pylera. Contact via medinfo@flynnpharma.com
11. Nyssen OP, Perez-Aisa A, Castro-Fernandez, M, and others. European registry on Helicobacter pylori management: Single-capsule bismuth quadruple therapy is effective in real-world clinical practice. United European Gastroenterol J. 2021;9:38–46 doi: 10.1177/2050640620972615