Helicobacter Pylori

oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

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

The full genetic code of H. pylori is now known. Specific genotypes are associated with severe morbidity. The most prevalent genotypes in patients with peptic ulcerations are vacA-positive and cagA-positive.

CagA-positive strains are more strongly associated with intestinal-type gastric cancer.

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  • The prevalence in 2008 was 30-40% in the UK adult population with pockets of higher prevalence associated with deprivation.[2] The prevalence has in fact decreased considerably over the period of a decade.[3]
  • Infection with H. pylori increases with age - the majority of 70 year-olds are infected but the prevalence is only 10-20% in children.[4]
  • Internationally, it is thought that 50% of all people are infected, although the exact prevalence is not known due to lack of information from undeveloped countries.[1]

50% of the population aged over 50 may be infected with H. pylori, so infection is not invariably associated with disease. 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).[5] Debate remains whether H. pylori is merely associated with, or is the cause of, duodenal ulceration.[6][7]

H. pylori-positive patients have at least a six-fold greater risk of developing gastric adenocarcinoma than do those without infection.[8]

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% of cases.[9] In the remaining 25%, there appears to be translocation of genes with oncogenic properties.

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.[10]

H. pylori infection may be asymptomatic - as above.

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

Alarm signs like weight loss, vomiting, haematemesis, anaemia or dysphagia at any age require urgent referral for endoscopy.[4]

Patients aged 55 years and older with unexplained and persistent recent-onset dyspepsia alone should also have endoscopy.
  • 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 with a 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. In those who test positive for H. pylori, eradication is more effective than simple acid suppression in that the number symptom-free after a year is 60% rather than 47%, giving an NNT of 7. Test and treat will reduce the number of endoscopies required, with significant savings.
  • As the prevalence of H. pylori is falling in the UK, a 30 year-old with dyspepsia may have a less than 20% chance of infection. Testing may however be worthwhile. The evidence is equivocal but there seems to be a subset of H. pylori-related dyspepsia patients who do improve on eradication therapy. Eradication without testing first is not recommended and likely to be very wasteful of resources, especially as this is likely to cause some dilemma when they return with symptoms.[11]
  • Eradication of H. pylori in patients who are about to start NSAIDs substantially reduces the risk of endoscopic and complicated ulcers.[12]

Non-invasive testing is useful only if it will alter the subsequent management of the patient. The National Institute for Health and Clinical Excellence (NICE) offers advice on which test to use:[4]

  • 13 C urea breath tests or stool antigen tests are the recommended way of testing for H. pylori. They are highly reliable for diagnosis. Stop antisecretories or bismuth two weeks before the test. They are also the most suitable test for assessing the success of eradication therapy at least four weeks after the end of treatment.
  • Serological tests are available for antibodies to H. pylori. They are very convenient but there is great variation in specificity and sensitivity of these tests. Serological testing has a sensitivity of 92% but only a specificity of 83%. This compares with breath testing that has a sensitivity of 95% and specificity of 96% and stool antigen testing with 95% and 94% respectively. These give predictive values (the likelihood that a positive test result is correct) of 64%, 88% and 84%, respectively. Hence, serological testing is more likely to lead to unnecessary eradication regimes. There is considerable variation between laboratories and the local validation should be known. Serological tests are no use for assessing eradication or relapse, as antibodies persist for a long while. Breath testing should be used in preference to stool antigen testing to check for eradication.
  • Endoscopy with biopsy for rapid urease test is highly reliable for both diagnosis and to confirm cure.

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.

The following is based on the recommendations of NICE.

Recommended first-line regimes
These are optimum regimens on current evidence:[4][13]
  • PAC regimen - double-dose PPI (eg 20 mg omeprazole) plus amoxicillin 1 g and clarithromycin 500 mg, all three given twice a day
  • PCM regimen - double-dose PPI (eg 20 mg omeprazole) plus metronidazole 400 mg and clarithromycin 250 mg, all three given twice a day.
Notes on first-line therapies:
  • One-week triple therapy regimens (a PPI plus two antibiotics) are recommended.[13] Two-week regimens are no more effective than one-week regimens[14] and can increase adverse effects. Dual therapy is not as effective as triple therapy.
  • Quadruple therapy (a PPI, bismuth, tetracycline, and metronidazole) is as effective as triple therapy, but taking 17 tablets per day does not make it a practical first-line option.
  • Double-dose PPIs are more effective than single-dose PPIs in PAC regimens. Eradication rate of 85.4% for double-dose PPIs and 78.5% for single-dose PPIs. The data were less clear for PCM regimens, due to much smaller patient numbers. Double-dose PPIs are therefore also recommended in PCM regimens as there are not enough data to support single dose PPIs clearly.
  • The dose of clarithromycin differs between the two regimens.
    • Pooled data for PAC regimens show eradication rates of 79.8% with clarithromycin 250 mg compared with 89.6% with clarithromycin 500 mg.
    • In PCM regimens, doubling the dose of clarithromycin had no statistically significant effect: eradication rates were 87.4% for clarithromycin 250 mg and 88.9% for clarithromycin 500 mg.


  • Although triple therapy using a PPI plus amoxicillin and metronidazole has previously been recommended as a first-line therapy, pooled data from four randomised, controlled trials have shown that it is less effective than either of the two triple therapies that contain clarithromycin.[4]
  • Tinidazole can be used as an alternative for patients who have adverse effects to metronidazole.[13]
  • Two-week eradication should be used in the case of a MALT lymphoma.
Second-line H. pylori eradication regimens
De-Noltab® 120 mg qds, tetracycline 500 mg qds, metronidazole 400 mg tds and once-daily PPI.[4][13]
  • Two randomised controlled trials comparing one-week quadruple therapy to one-week triple therapy found that both types of eradication therapy seemed equally effective.[14] Quadruple therapy is therefore preferred as second-line therapy since it is likely to be more effective than a PPI, amoxicillin, metronidazole (PAM) regimen. It can also be used by people who are penicillin-hypersensitive.
  • The recommendation to use an alternative triple therapy regimen if quadruple therapy is not tolerated is based on consensus.[15]


It would seem sensible to use a regimen with a different combination of antibiotics as second-line eradication therapy. The inclusion of tetracycline as one of these antibiotics is a pragmatic recommendation since there is no evidence to guide which second-line triple-therapy regimens should be offered to people with penicillin hypersensitivity. However, the efficacy of the suggested combinations of a PPI, metronidazole, and tetracycline, or a PPI, clarithromycin, and tetracycline, is unknown, as they have not been studied in randomised controlled trials. Levofloxacin is a proposed alternative which is increasingly being used.[16]

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 regimen 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; resistant rates vary across the UK.[17]

Antibiotic resistance

It would be reasonable to have local protocols based upon local patterns of antibiotic resistance.[18] Resistance to metronidazole (in particular) is highly variable.

  • The Health Protection Agency reports that the prevalence of H. pylori antibiotic resistance varies within the UK depending on location. It is around 20-63% for metronidazole and 4.4-11% for clarithromycin.[17]
  • Metronidazole resistance is low in rural areas within the UK but can be as high as 65% in urban areas with large immigrant populations.
  • 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. European guidelines recommend culture before treatment based on the microbial antibiotic sensitivity in such circumstances.[19]

  • Eradication therapy reduces duodenal ulcer recurrence in H. pylori-positive patients.
  • After 3 to 12 months, 39% of patients receiving short-term acid suppression therapy are without ulcer compared with 91% who received eradication therapy - an NNT of 2. The size of this benefit varies between trials.
  • For gastric ulcer the figures are that 3 to 12 months later 45% of patients receiving short-term acid suppression therapy are without ulcer compared with 87% after eradication - an NNT of 3.
  • Re-infection rates are variable. One study reported a re-infection rate of 1.8%. Developed countries had lower re-infection rates than developing countries.[20]
  • Eradication therapy is much cheaper than long-term acid suppression with either PPI or H2-receptor antagonist.[21]
  • It is only necessary to check for H. pylori eradication in patients whose symptoms return.
  • 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 separate article Peptic Ulcer Disease for details concerning the management of non-healing ulcers.

  • Studies suggest that probiotics and lactobacilli reduce the activity of H. pylori.[23]
  • 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.[24]
  • H. pylori infection has been implicated in the aetiology of coronary heart disease but this has recently been refuted.[25] Likewise, evidence linking cirrhosis, gastroduodenal ulcers and H.pylori is lacking.[26]

There is also ongoing work to produce a vaccine against the organism.[27]

Further reading & references

  • Graham DY, Shiotani A; New concepts of resistance in the treatment of Helicobacter pylori infections. Nat Clin Pract Gastroenterol Hepatol. 2008 Jun;5(6):321-31. Epub 2008 Apr 29.
  • Sweeney EG, Guillemin K; A gastric pathogen moves chemotaxis in a new direction. MBio. 2011 Sep 20;2(5). pii: e00201-11. doi: 10.1128/mBio.00201-11. Print 2011.
  1. Santacroce L et al, Helicobacter Pylori Infection, Medscape, Sep 2011
  2. Fuccio L, Laterza L, Zagari RM, et al; Treatment of Helicobacter pylori infection. BMJ. 2008 Sep 15;337:a1454. doi: 10.1136/bmj.a1454.
  3. Cancer Research UK; Cancer incidence for common cancers - UK statistics, 2011.
  4. Dyspepsia: Managing dyspepsia in adults in primary care; NICE Clinical Guideline (2004)
  5. Yeomans ND; The ulcer sleuths: The search for the cause of peptic ulcers. J Gastroenterol Hepatol. 2011 Jan;26 Suppl 1:35-41. doi:
  6. Hobsley M, Tovey FI, Bardhan KD, et al; Does Helicobacter pylori really cause duodenal ulcers? No. BMJ. 2009 Aug 14;339:b2788. doi: 10.1136/bmj.b2788.
  7. Ford AC, Talley NJ; Does Helicobacter pylori really cause duodenal ulcers? Yes. BMJ. 2009 Aug 14;339:b2784. doi: 10.1136/bmj.b2784.
  8. Hartgrink HH, Jansen EP, van Grieken NC, et al; Gastric cancer. Lancet. 2009 Aug 8;374(9688):477-90. Epub 2009 Jul 20.
  9. Isaacson PG; Update on MALT lymphomas.; Best Pract Res Clin Haematol. 2005 Mar;18(1):57-68.
  10. Nam SY; Helicobacter pylori Has an Inverse Relationship With Severity of Reflux J Neurogastroenterol Motil. 2011 Jul;17(3):209-10. Epub 2011 Jul 13.
  11. Delaney BC, Moayyedi P, Forman D; Initial management strategies for dyspepsia. Cochrane Database Syst Rev. 2003;(2):CD001961.
  12. Should You Eradicate Helicobacter Pylori Prior to Chronic NSAID Treatment? - Smith J; Clinical Correlations, 2011
  13. British National Formulary
  14. Delaney BC, Moayyedi P and Forman D (2003a), Initial management strategies for dyspepsia (Cochrane Review). The Cochrane Library. Issue 2. Chichester, UK: John Wiley & Sons Ltd
  15. Malfertheiner P, Dent J, Zeijlon L, et al; Impact of Helicobacter pylori eradication on heartburn in patients with gastric or duodenal ulcer disease -- results from a randomized trial programme.; Aliment Pharmacol Ther. 2002 Aug;16(8):1431-42.
  16. Gisbert JP; Second-line rescue therapy of helicobacter pylori infection. Therap Adv Gastroenterol. 2009 Nov;2(6):331-56.
  17. Surveillance of Helicobacter pylori antibiotic resistance in England and Wales, Health Protection Agency, 2008
  18. 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;53(Pt 6):535-8.
  19. Suzuki H, Nishizawa T, Hibi T; Helicobacter pylori eradication therapy. Future Microbiol. 2010 Apr;5(4):639-48.
  20. Silva FM, Navarro-Rodriguez T, Barbuti RC, et al; Helicobacter pylori reinfection in Brazilian patients with peptic ulcer disease: Helicobacter. 2010 Feb;15(1):46-52.
  21. Mason JM, Raghunath AS, Hungin AP, et al; Helicobacter pylori eradication in long-term proton pump inhibitor users is Aliment Pharmacol Ther. 2008 Dec 1;28(11-12):1297-303. Epub 2008 Sep 14.
  22. de Wit NJ, Mendive J, Seifert B, et al; Guidelines on the management of H.pylori in primary care: development of an Fam Pract. 2000 Aug;17 Suppl 2:S27-32.
  23. de Vrese M, Kristen H, Rautenberg P, et al; Probiotic lactobacilli and bifidobacteria in a fermented milk product with added J Dairy Res. 2011 Nov;78(4):396-403. Epub 2011 Aug 26.
  24. Does treatment of asymptomatic H pylori infection reduce the risk of gastric cancer?, NHS Education for Scotland, 2009
  25. Christodoulou DK, Milionis HJ, Pappa P, et al; Association of Helicobacter pylori infection with cardiovascular disease--is it Eur J Intern Med. 2011 Apr;22(2):191-4. Epub 2010 Dec 23.
  26. Kirchner GI, Beil W, Bleck JS, et al; Prevalence of Helicobacter pylori and occurrence of gastroduodenal lesions in Int J Clin Exp Med. 2011;4(1):26-31. Epub 2010 Dec 25.
  27. Aebischer T, Meyer TF, Andersen LP; Inflammation, immunity, and vaccines for Helicobacter. Helicobacter. 2010 Sep;15 Suppl 1:21-8. doi: 10.1111/j.1523-5378.2010.00777.x.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Laurence Knott
Current Version:
Peer Reviewer:
Dr Hannah Gronow
Last Checked:
19/01/2012
Document ID:
334 (v6)
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