Helicobacter Pylori

Authored by , Reviewed by Dr Hayley Willacy | Last edited | Meets Patient’s editorial guidelines

This article is for Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Helicobacter Pylori article more useful, or one of our other health articles.


Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.

Helicobacter pylori is a motile, Gram-negative, curved or spiral bacillus. It was originally named Campylobacter pyloridis. It was then renamed C. pylori and later H. pylori, as its structure became better identified.

H. pylori can be classified into seven population types - hpAfrica1, hpAfrica2, hpNEAfrica, hpEastAsia, hpAsia2, hpEurope and hpSahul[1]. Complete genomes of several of these types have now been worked out[2]. The most prevalent genotypes in patients with peptic ulcerations are vacA-positive and cagA-positive[3].

The presence of vacA, cagA and other strains of H. pylori is strongly associated with intestinal-type gastric cancer[4].

  • The prevalence of H. pylori in many areas of the UK is lower than 15% and continues to fall[5].
  • Risk factors include lower socio-economic status and unsanitary conditions or over-crowding. The prevalence of H. pylori is higher in developing countries[6].
  • As a general rule, the prevalence of H. pylori increases with age[7].
  • Globally, more than 50% of all people are infected[8].

More than 50% of the world's population are infected with H. pylori, so infection is not invariably associated with disease[8]. However, it is present in almost all cases of duodenal ulcer and most cases of gastric ulcer. The recognition of the association between H. pylori infection and peptic ulcer disease was a major breakthrough in gastroenterology. Peptic ulcer is rare without either H. pylori or non-steroidal anti-inflammatory drugs (NSAIDs)[9]. There has been some debate about whether H. pylori is a cause of duodenal ulcer or whether the two are simply associated. There is a considerable weight of evidence supporting the latter, including the finding that a high proportion of children who have duodenal ulcer disease test positive for H. pylori[10].

H. pylori-positive patients have an increased risk of developing gastric adenocarcinoma, but the link is not a simple one. The association largely depends on the potential for H. pylori to cause atrophic gastritis. Whilst the eradication of H. pylori can reduce the oncogenic risk, once metaplasia is established, this becomes less likely[11].

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a rare but interesting condition in that eradication of H. pylori causes clinical regression of the lymphoma in 75-80% of cases[12]. In the remaining, there appears to be translocation of genes with oncogenic properties[13].

The association between H. pylori infection and gastro-oesophageal reflux disease remains controversial. In fact some studies suggest that there is an inverse relationship and that its presence may confer a protective effect against reflux oesophagitis[14].

H. pylori infection may be asymptomatic - as above.

There may be symptoms of peptic ulcer disease (dyspepsia) - eg, fullness, bloating, early satiety and nausea.

Refer patients urgently who are aged 55 years and older and have dyspepsia and weight loss. Consider non-urgent referral for patients aged 55 years and older with treatment-resistant dyspepsia, or dyspepsia with raised platelet count, or nausea or vomiting.
  • Review medications for possible causes of dyspepsia - eg, calcium antagonists, nitrates, theophyllines, bisphosphonates, corticosteroids and NSAIDs. In patients requiring referral, suspend NSAID use. Consider the possibility of cardiac or biliary disease as part of the differential diagnosis.
  • Either empirical treatment for four weeks with a full-dose proton pump inhibitor (PPI) or testing for and treating H. pylori may be employed. Current evidence offers no guidance on preference.
  • A two-week washout period following PPI use is necessary before testing for H. pylori with a breath test or a stool antigen test.
  • If there is failure to resolve, or relapse on stopping acid suppression, evidence suggests testing and treating H. pylori if the test is positive.
  • A Cochrane review concluded that H. pylori eradication therapy without testing first is not recommended and is likely to be very wasteful of resources, especially as this is likely to cause some dilemma if the patient returns with symptoms[17]. This review, published in 2003, does not appear to have been updated, possibly because the increasing emphasis on antibiotic stewardship renders such a hypothesis unethical.
  • Eradication of H. pylori in patients who are about to start NSAIDs substantially reduces the risk of endoscopic and complicated ulcers[18].

Editor's note

Dr Sarah Jarvis, 11th February 2021

In September 2020 and more recently in January 2021, the National Institute for Health and Care Excellence (NICE) updated its suspected cancer recognition and referral guidance. However, there are no changes in these updates which relate to this H. pylori article[16].

Non-invasive testing is useful only if it will alter the subsequent management of the patient. NICE offers advice on which test to use[15]:

  • 13C urea breath tests or stool antigen tests are the recommended way of testing for H. pylori, although laboratory-based serology can be used if locally validated. Stop antisecretories or bismuth two weeks before the test.
  • The breath test is the only currently validated method for assessing eradication in primary care.

Offer eradication therapy to all patients with positive tests for H. pylori.

There are several regimes. There is probably no difference between the various PPIs available, provided that they are used at the equivalent dose and this is a matter of personal choice.

Increasing concerns about resistance prompted NICE to change their antibiotic guidance in 2019. The following is based on their recommendations[15, 19].

Recommended first-line regimes
These are optimum regimes on current evidence:
  • A seven-day course of PPI plus either amoxicillin 1 g and either clarithromycin 500 mg or metronidazole 400 mg - all three given twice a day.
  • Choose the treatment regime with the lowest acquisition cost and take into account previous exposure to clarithromycin or metronidazole.
  • For people allergic to penicillin use a PPI, clarithromycin and metronidazole - all twice a day for seven days.
  • For people allergic to penicillin who have previously been exposed to clarithromycin, use a PPI, metronidazole, tetracycline and bismuth.
Second-line H. pylori eradication regimes
  • For people who do not respond to first-line therapy, offer a PPI, amoxicillin and either clarithromycin or metronidazole (whichever was not used first-line).
  • For people who have had previous exposure to clarithromycin and metronidazole, offer a seven‑day, twice-daily course of treatment with a tetracycline (or if tetracycline cannot be used, levofloxacin).
  • For people who are allergic to penicillin and who have not had previous exposure to a quinolone), offer a seven‑day, twice-daily course of a PPI, and metronidazole and levofloxacin.
  • For people who are allergic to penicillin and who have had previous exposure to a quinolone, a seven-day course of a PPI, bismuth, metronidazole and tetracycline.

If there is failure of treatment, this is usually due to poor compliance or to antibiotic resistance:

  • If there was poor compliance, a more tolerable regime may be required. Abdominal discomfort and diarrhoea are very common but the patient should be encouraged to persist to achieve eradication.
  • Resistance can even develop during treatment, especially with a single antibiotic.
  • Metronidazole and clarithromycin are the antibiotics most implicated in resistance; resistance rates vary across the UK[20]

Antibiotic resistance

Global research suggests that it would be reasonable to have local protocols based upon local patterns of antibiotic resistance[21]. Resistance to metronidazole (in particular) is highly variable.

  • European study findings of H. pylori resistance rates in adults were 17.5% for clarithromycin, 14.1% for levofloxacin, and 34.9% for metronidazole. Resistance rates were significantly higher for clarithromycin and levofloxacin in Western/Central and Southern Europe (>20%) than in Northern European countries (<10%)[22].
  • Metronidazole resistance is low in rural areas within the UK but can be as high as 65% in urban areas with large immigrant populations[23].
  • Amoxicillin resistance is rare but does occur.
  • Resistance can be acquired during treatment.

Patients who are not cured with two consecutive treatments, including clarithromycin and metronidazole, will have at least single and usually double resistance. No standard third-line therapy exists, although isolated studies have reported success with a PPI, bismuth subcitrate, tetracycline and metronidazole[24]. Seek specialist advice if second-line therapy fails. Logically, further treatment should be based on culture before treatment, but one study found that this approach often failed to eradicate H. pylori infection[25].

  • There is definitive evidence that eradicating H. pylori improves remission rates for gastric and duodenal ulcers and is superior and more cost-effective than maintenance acid suppressive therapy in preventing duodenal ulcer.
  • One study found that H. pylori eradication was more successful in decreasing recurrent gastroduodenal ulcer bleeding than ulcer healing treatment alone.
  • H. pylori eradication is beneficial in patients with dyspepsia who have been identified as H. pylori-positive but have not had an endoscopy ('test and treat')[15].
  • H. pylori eradication has been proposed as first-line treatment for infected patients with stage I low-grade gastric MALT lymphoma.
  • The evidence concerning the protective effect of H. pylori against gastric carcinoma is complex but the consensus is that it should be eradicated as soon as possible and best before pre-cancerous lesions are present (see Sequelae of Helicobacter pylori section above).
  • Re-infection rates are variable. A systematic review reported a global re-infection rate of 3.1%. Developed countries had lower re-infection rates compared with those of developing countries[27].
  • In dyspepsia it is only necessary to check for H. pylori eradication in patients whose symptoms return.
  • Patients with peptic ulcer should have a re-test (gastric or duodenal) six to eight weeks after beginning treatment.
  • Serology can remain positive for up to one year after eradication.
  • If the patient was taking NSAIDs it will be necessary to discuss further management.
  • Low-dose misoprostol is less effective than acid suppression.

See the separate Peptic Ulcer Disease article for details concerning the management of non-healing ulcers.

  • Studies suggest that probiotics and lactobacilli reduce the activity of H. pylori. One study reported that the use of probiotics before and during eradication treatment improved eradication effects. The best results were obtained when probiotics were used for more than two weeks[28].
  • It is generally advocated that H. pylori testing should be driven purely to confirm an infection as the cause of disease and then to eradicate it.
  • The risk:benefit ratio of H. pylori eradication in asymptomatic patients requires further evaluation. A large trial of Asian patients provided moderate evidence that eradication reduced the risk of gastric carcinoma but studies of patients from other ethnic communities are required[29].
  • H. pylori infection has been implicated in the aetiology of coronary heart disease via an autoimmune mechanism but further research is required[30]. Likewise, H. pylori has been linked to non-alcoholic fatty liver disease, but more information is required[31].

Work to produce a vaccine against the organism has slowed as the resources of the large pharmaceutical companies have been directed towards other priorities[32].

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Further reading and references

  • Hu Y, Zhu Y, Lu NH; Recent progress in Helicobacter pylori treatment. Chin Med J (Engl). 2020 Feb 5133(3):335-343. doi: 10.1097/CM9.0000000000000618.

  • Pohl D, Keller PM, Bordier V, et al; Review of current diagnostic methods and advances in Helicobacter pylori diagnostics in the era of next generation sequencing. World J Gastroenterol. 2019 Aug 2825(32):4629-4660. doi: 10.3748/wjg.v25.i32.4629.

  • Li H, Xu CX, Gong RJ, et al; How does Helicobacter pylori cause gastric cancer through connexins: An opinion review. World J Gastroenterol. 2019 Sep 2125(35):5220-5232. doi: 10.3748/wjg.v25.i35.5220.

  1. Lamichhane B, Chua EG, Wise MJ, et al; The complete genome and methylome of Helicobacter pylori hpNEAfrica strain HP14039. Gut Pathog. 2019 Feb 2011:7. doi: 10.1186/s13099-019-0284-y. eCollection 2019.

  2. Dawson EM, Dunne KA, Richardson EJ, et al; Complete genome sequence of Helicobacter pylori B128 7.13 and a single-step method for the generation of unmarked mutations. Helicobacter. 2019 Aug24(4):e12587. doi: 10.1111/hel.12587. Epub 2019 May 7.

  3. Memon AA, Hussein NR, Miendje Deyi VY, et al; Vacuolating cytotoxin genotypes are strong markers of gastric cancer and duodenal ulcer-associated Helicobacter pylori strains: a matched case-control study. J Clin Microbiol. 2014 Aug52(8):2984-9. doi: 10.1128/JCM.00551-14. Epub 2014 Jun 11.

  4. Testerman TL, Morris J; Beyond the stomach: An updated view of pathogenesis, diagnosis, and treatment. World J Gastroenterol. 2014 Sep 2820(36):12781-12808.

  5. Test and treat for Helicobacter pylori (HP) in Dyspepsia - Quick Reference Guide for Primary Care; Public Health England

  6. Narayanan M, Reddy KM, Marsicano E; Peptic Ulcer Disease and Helicobacter pylori infection. Mo Med. 2018 May-Jun115(3):219-224.

  7. Hunt RH, Xiao SD, Megraud F, et al; Helicobacter pylori in developing countries. World Gastroenterology Organisation Global Guideline. J Gastrointestin Liver Dis. 2011 Sep20(3):299-304.

  8. Rizwan M, Fatima N, Alvi A; Epidemiology and pattern of antibiotic resistance in Helicobacter pylori: scenario from Saudi Arabia. Saudi J Gastroenterol. 2014 Jul-Aug20(4):212-8. doi: 10.4103/1319-3767.136935.

  9. Yeomans ND; The ulcer sleuths: The search for the cause of peptic ulcers. J Gastroenterol Hepatol. 2011 Jan26 Suppl 1:35-41. doi:

  10. Hernandez C, Serrano C, Einisman H, et al; Peptic Ulcer Disease in Helicobacter Pylori-Infected Children: Clinical Findings and Mucosal Immune Response. J Pediatr Gastroenterol Nutr. 2014 Jul 21.

  11. Diaz P, Valenzuela Valderrama M, Bravo J, et al; Helicobacter pylori and Gastric Cancer: Adaptive Cellular Mechanisms Involved in Disease Progression. Front Microbiol. 2018 Jan 229:5. doi: 10.3389/fmicb.2018.00005. eCollection 2018.

  12. Zullo A, Hassan C, Ridola L, et al; Gastric MALT lymphoma: old and new insights. Ann Gastroenterol. 201427(1):27-33.

  13. Troppan K, Wenzl K, Neumeister P, et al; Molecular Pathogenesis of MALT Lymphoma. Gastroenterol Res Pract. 20152015:102656. doi: 10.1155/2015/102656. Epub 2015 Apr 1.

  14. Adhami H, Zimmermann B; [Linear- and Areal-analytical results of the karyometric studies on monolayer cultures and the influence of actinomycin (author's transl)]. Arzneimittelforschung. 197626(1):22-6.

  15. Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management; NICE Clinical Guideline (Sept 2014 - last updated October 2019)

  16. Suspected cancer: recognition and referral; NICE Clinical Guideline (2015 - last updated January 2021)

  17. Delaney BC, Moayyedi P, Forman D; Initial management strategies for dyspepsia. Cochrane Database Syst Rev. 2003(2):CD001961.

  18. Should You Eradicate Helicobacter Pylori Prior to Chronic NSAID Treatment?; Clinical Correlations, 2011

  19. British National Formulary (BNF); NICE Evidence Services (UK access only)

  20. McNulty CA, Lasseter G, Shaw I, et al; Is Helicobacter pylori antibiotic resistance surveillance needed and how can it be delivered? Aliment Pharmacol Ther. 2012 May35(10):1221-30. doi: 10.1111/j.1365-2036.2012.05083.x. Epub 2012 Apr 2.

  21. Mascellino MT, Porowska B, De Angelis M, et al; Antibiotic susceptibility, heteroresistance, and updated treatment strategies in Helicobacter pylori infection. Drug Des Devel Ther. 2017 Jul 2811:2209-2220. doi: 10.2147/DDDT.S136240. eCollection 2017.

  22. Megraud F, Coenen S, Versporten A, et al; Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut. 2013 Jan62(1):34-42. doi: 10.1136/gutjnl-2012-302254. Epub 2012 May 12.

  23. Cameron EA, Powell KU, Baldwin L, et al; Helicobacter pylori: antibiotic resistance and eradication rates in Suffolk, UK, 1991-2001. J Med Microbiol. 2004 Jun

  24. Gisbert JP, Perez-Aisa A, Rodrigo L, et al; Third-line rescue therapy with bismuth-containing quadruple regimen after failure of two treatments (with clarithromycin and levofloxacin) for H. pylori infection. Dig Dis Sci. 2014 Feb59(2):383-9. doi: 10.1007/s10620-013-2900-x. Epub 2013 Oct 15.

  25. Costa S, Soares JB, Goncalves R; Efficacy and tolerability of culture-guided treatment for Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 2017 Nov29(11):1258-1263. doi: 10.1097/MEG.0000000000000960.

  26. Pichichero ME; A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients. Pediatrics. 2005 Apr115(4):1048-57.

  27. Hu Y, Wan JH, Li XY, et al; Systematic review with meta-analysis: the global recurrence rate of Helicobacter pylori. Aliment Pharmacol Ther. 2017 Nov46(9):773-779. doi: 10.1111/apt.14319. Epub 2017 Sep 11.

  28. Shi X, Zhang J, Mo L, et al; Efficacy and safety of probiotics in eradicating Helicobacter pylori: A network meta-analysis. Medicine (Baltimore). 2019 Apr98(15):e15180. doi: 10.1097/MD.0000000000015180.

  29. Ford AC, Forman D, Hunt RH, et al; Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials. BMJ. 2014 May 20348:g3174. doi: 10.1136/bmj.g3174.

  30. Mladenova I; Helicobacter pylori and cardiovascular disease: update 2019. Minerva Cardioangiol. 2019 Oct67(5):425-432. doi: 10.23736/S0026-4725.19.04986-7. Epub 2019 Jul 24.

  31. Zhou BG, Yang HJ, Xu W, et al; Association between Helicobacter pylori infection and nonalcoholic fatty liver disease: A systematic review and meta-analysis of observational studies. Helicobacter. 2019 Jun24(3):e12576. doi: 10.1111/hel.12576. Epub 2019 Mar 25.

  32. Sutton P, Boag JM; Status of vaccine research and development for Helicobacter pylori. Vaccine. 2019 Nov 2837(50):7295-7299. doi: 10.1016/j.vaccine.2018.01.001. Epub 2018 Apr 5.

I finished my week's triple therapy for H Pylori a week ago. Since have felt OK....had an awful day of diarrhoea around 3 days later, since then stools returning to normal colour and consistency....

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