Helicobacter pylori Infection in adults

Publication: 01/01/2008  
Last review: 25/08/2017  
Next review: 25/08/2020  
Clinical Guideline
CURRENT 
ID: 1210 
Approved By: Improving Antimicrobial Prescribing Group & LAPC 
Copyright© Leeds Teaching Hospitals NHS Trust 2017  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guideline for Treatment of Helicobacter pylori Infection in Adults

Summary
Helicobacter pylori Infection in adults

  1. Who should be tested for H. pylori?
    • Patients with uncomplicated dyspepsia that is unresponsive to lifestyle change and antacids, following a single one month course of proton pump inhibitor (PPI), without alarm symptoms (see below). In patients aged 55 years and older with unexplained and persistent recent-onset dyspepsia alone, an urgent referral for endoscopy should be made
    • Patients with peptic ulcer disease
    • Patients with gastric cancer (particularly if undergoing curative endoscopic therapy or partial gastrectomy)
    • Patients with functional dyspepsia (dyspepsia in the presence of a structurally normal upper endoscopy)
    • Patients with a first degree relative with gastric cancer
    • Patients with MALToma

  2. Investigations required- one of the following:
    • Stool sample (faecal antigen test)
    • CLO test (Campylobacter-like organism or rapid urease test - requires biopsy during endoscopy)

  3. Non-Antimicrobial Management
    • The following washout periods are recommended before testing for H. pylori
      • PPIs – 2 weeks
      • Bismuth and antibiotics - 4 weeks
      • H2-receptor Antagonists – 48 hours
    • Follow NICE guidance for other non-antimicrobial treatment of uninvestigated dyspepsia, peptic ulcer disease, and functional dyspepsia.
       https://www.nice.org.uk/guidance/cg184

  4. Antimicrobial treatment - Who should be treated for H. pylori?

    Offer treatment to all patients newly diagnosed with H. pylori according to Table 1.
    Do not use clarithromycin or metronidazole if patient has a history of use in the past year for any infection.
    Do not retest or retreat for uninvestigated dyspepsia or functional dyspepsia

Table 1. First and second line regimens for H. pylori eradication

First line

First line (Penicillin allergic patient)

First line (Penicillin allergic patient and previous exposure to clarithromycin)*

 

Lansoprazole electronic Medicines Compendium information on Lansoprazole 30mg po 12-hourly
AND 
Amoxicillin electronic Medicines Compendium information on Amoxicillin1g po 12-hourly
AND EITHER
Clarithromycin electronic Medicines Compendium information on Clarithromycin 500mg po 12-hourly
OR
Metronidazole electronic Medicines Compendium information on Metronidazole 400mg 12-hourly

Lansoprazole electronic Medicines Compendium information on Lansoprazole 30mg po 12-hourly
AND 
Clarithromycin electronic Medicines Compendium information on Clarithromycin250mg po 12-hourly
AND 
Metronidazole electronic Medicines Compendium information on Metronidazole 400mg 12-hourly

Lansoprazole electronic Medicines Compendium information on Lansoprazole 30mg 12-hourly
AND 
Metronidazole electronic Medicines Compendium information on Metronidazole400mg 8-hourly
AND
Doxycycline electronic Medicines Compendium information on Doxycycline 100mg 12-hourly
AND
Bismuth subsalicylate (Peptobismol) 525mg 6-hourly

 

Second line

Second line (previous exposure to clarithromycin and metronidazole)

Second line (Penicillin allergic patient)

Second line (Penicillin allergic patient and previous exposure to a quinolone)*

Lansoprazole electronic Medicines Compendium information on Lansoprazole 30mg po 12-hourly
AND
Amoxicillin electronic Medicines Compendium information on Amoxicillin 1g po 12-hourly
AND EITHER
Clarithromycin electronic Medicines Compendium information on Clarithromycin 500mg po 12-hourly
OR
Metronidazole electronic Medicines Compendium information on Metronidazole 400mg 12-hourly (whichever was not used first line)

Lansoprazole electronic Medicines Compendium information on Lansoprazole 30mg po 12-hourly
AND
Amoxicillin electronic Medicines Compendium information on Amoxicillin 1g po 12-hourly
AND EITHER
Levofloxacin electronic Medicines Compendium information on Levofloxacin 250mg po 12 hourly
OR
Doxycycline electronic Medicines Compendium information on Doxycycline 100mg 12-hourly

Lansoprazole electronic Medicines Compendium information on Lansoprazole 30mg po 12-hourly
AND
Metronidazole electronic Medicines Compendium information on Metronidazole 400mg 12-hourly
AND
Levofloxacin electronic Medicines Compendium information on Levofloxacin 250mg po 12 hourly

Lansoprazole electronic Medicines Compendium information on Lansoprazole 30mg po 12-hourly
AND
Bismuth subsalicylate (Peptobismol) 525mg 6-hourly
AND
Metronidazole electronic Medicines Compendium information on Metronidazole 400mg 8-hourly
AND
Doxycycline electronic Medicines Compendium information on Doxycycline 100mg 12-hourly

*Previous second line therapy for LTH guidelines is a quadruple therapy including tripotassium dicitratobismuthate 240mg 6-hourly (Denol). Denol manufacture was discontinued early 2016. Bismuth Subsalicylate (Peptobismol) 525mg 6-hourly will be substituted for Denol. This alternative is supported by PHE guidelines and American guidelines.

Leave at least 4 weeks before retesting after eradication for PUD, gastric cancer or MALToma

Duration of treatment
First line and second line therapy: 7 days
MALToma: 14 days

Referral criteria

  • Failure of eradication with second line regimens (peptic ulcer disease or MALToma only) contact Gastroenterology for advice

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Background

The gastric bacterium H. pylori is widely present in the population but causes no harm in the majority of patients. H. pylori prevalence is approximately 40% in the UK, though the prevalence increases with age. This may be largely a cohort effect - most individuals acquire the infection in childhood, and poorer socioeconomic conditions 70 years ago meant most children were infected. There is now substantial evidence that peptic ulcer disease may be cured by eradicating H. pylori. The potential to reduce gastric cancer and ameliorate functional dyspepsia is less clear.1

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Clinical Diagnosis

Criteria for use of guidelines (Evidence level A)
Patients with one of the following should be tested

  • Uninvestigated dyspepsia - At 12 months, there were no significant differences in QALYs, costs, or dyspeptic symptoms between the group assigned to initial H. pylori test and treat and the group assigned to initial acid suppression2 In patients with alarm features (dysphagia, odyophagia, haematemesis or melaena, persistent vomiting, unintentional weight loss, iron deficiency anaemia, family history of gastric cancer, palpable epigastric mass), and those aged 55 years and older with unexplained and persistent recent-onset dyspepsia alone, an urgent referral for endoscopy should be made
  • Peptic ulcer disease - Eradication of H. pylori has been shown to speed up healing of duodenal ulcers as compared to acid suppression alone. After 4 to 8 weeks, patients receiving acid suppression average 69% healing, eradication increases this by a further 5.4%, a NNT of 18. Healing of gastric ulcers is not increased by H. pylori eradication. The principal benefit in eradication is the reduction in recurrence rates, thereby removing the need for long term acid suppression therapy. For duodenal ulcers 39% of patients receiving short term acid suppression are without ulcer after 3-12 months, eradication increases this by 52% (NNT 2). For gastric ulcers the equivalent figures are 45% increased by a further 32% by eradication (NNT 3)1
  • Functional dyspepsia (dyspepsia in the presence of a structurally normal upper endoscopy) - Symptoms will naturally improve in 36% of patients; 7% will improve due to eradication therapy but 57% of substantial symptoms will remain over a 3–12 month period.1
  • Gastric cancer (particularly if undergoing curative endoscopic therapy or partial gastrectomy). There is evidence that the incidence of metachronous gastric cancer is reduced with eradication therapy compared to no treatment.
  • A first degree relative with gastric cancer
  • MALToma

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Investigation

Recommendation: either of the following tests can be used to diagnose H. pylori infection:

  1. Stool sample (faecal antigen test)
  2. CLO test (Campylobacter-like organism or rapid urease test) - requires biopsy during endoscopy
    [Evidence level C]
  • Evidence from evaluations of diagnostic test accuracy show that serological testing (sensitivity 92%, specificity 83%) performs less well than breath testing (sensitivity 95%, specificity 96%) and stool antigen testing (sensitivity 95%, specificity 94%). The resultant lower positive predictive value* (64% vs. 88% or 84%, respectively) leads to concerns about the unnecessary use of antibiotics when serology testing is used. CLO testing also provides high sensitivity and specificity1.
  • Recent use of PPIs, antibiotics, bismuth and possibly H2-receptor antagonists can increase the possibility of a false negative test1,6.

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Treatment

Antimicrobial treatment (Evidence level A)

  • Eradication is effective in 80–85% of patients.
  • Clarithromycin electronic Medicines Compendium information on Clarithromycin 250 mg twice-daily is as effective as 500 mg twice-daily when combined with Metronidazole electronic Medicines Compendium information on Metronidazole1.
  • PPI, Amoxicillin electronic Medicines Compendium information on AmoxicillinClarithromycin electronic Medicines Compendium information on Clarithromycin 500 mg (PAC500) regimens and PPI, Metronidazole electronic Medicines Compendium information on MetronidazoleClarithromycin electronic Medicines Compendium information on Clarithromycin 250 mg (PMC250) regimens achieve the same eradication rate1.
  • Clarithromycin electronic Medicines Compendium information on Clarithromycin resistance is an important risk factor for treatment failure. In a meta-analysis, Clarithromycin electronic Medicines Compendium information on Clarithromycin resistance reduced efficacy by 66% for PAC regimens, and 35% in PMC regimens3.
  • Metronidazole electronic Medicines Compendium information on Metronidazole resistance seems to be less important. Resistance decreased efficacy by 18% for PMC regimens and by 14% in bismuth based quadruple therapy regimens.3
  • European guidelines support bismuth based quadruple therapy as a second line therapy or an alternative first line therapy.4
  • Individuals prescribed an antibiotic in primary care for a respiratory or urinary infection develop bacterial resistance to that antibiotic. The effect is greatest in the month immediately after treatment but may persist for up to 12 months5. As resistance to Clarithromycin electronic Medicines Compendium information on Clarithromycin in H. pylori is the principal concern, the group felt it was reasonable to apply this to the use of Clarithromycin electronic Medicines Compendium information on Clarithromycin in H. pylori eradication

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Duration of Treatment

Duration of treatment (Evidence level A)

  • Although 14-day therapy gives an almost 10% higher eradication rate, the absolute benefit of H. pylori therapy is relatively modest in functional dyspepsia and uninvestigated dyspepsia and the longer duration of therapy does not appear cost-effective. In patients with peptic ulcer, increasing the course to 14 days duration improves the effectiveness of eradication by nearly 10% but does not appear cost-effective1

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Treatment Failure
Please contact Microbiology if the patient is not responding to the recommended antimicrobial regimens.

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Referral Criteria
As agreed by authors of these guidelines

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Provenance

Record: 1210
Objective:

Aims

  • To improve the diagnosis and management of Helicobacter pylori infection

Objectives

  • To provide evidence-based recommendations for appropriate investigation of Helicobacter pylori infection
  • To provide evidence-based recommendations for appropriate empirical or directed antimicrobial therapy of Helicobacter pylori infection
  • To recommend appropriate dose, route of administration, and duration of antimicrobial agents
  • To advise in the event of antimicrobial allergy
  • To set-out criteria for referral to specialists
Clinical condition:

Helicobacter Pylori Infection

Target patient group: Adults
Target professional group(s): Secondary Care Doctors
Pharmacists
Primary Care Doctors
Primary Care Nurses
Secondary Care Nurses
Adapted from:

Adapted from: NICE. Clinical Guideline [CG184) Gastro-oesophageal reflux disease and dyspepsis in adults: investigation and management. NICE 2014, London. (https://www.nice.org.uk/guidance/cg184/chapter/1-recommendations?unlid=6240325232015794309#helicobacter-pylori-testing-and-eradication)


Evidence base

References:

  1. North of England Dyspepsia Guideline Development Group (2004). Dyspepsia – managing dyspepsia in adults in primary care. Centre for Health Services Research report no 112 [online].Newcastle, University of Newcastle. Available from the World Wide Web: [Accessed 4th Aug 2006]
  2. Delaney BC, Qume M, Moayyedi P, Logan RFA, Ford AC, Elliott C, McNulty C, Wilson S, Hobbs FDR. Helicobacter pylori test and treat versus proton pump inhibitor in initial management of dyspepsia in primary care: multicentre randomised controlled trila (MRC-CUBE trial). British Medical Journal 2008; 336: 651-654.
  3. Fischbach L and Evans EL. Meta-analysis: the effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapies for Helicobacter pylori. Alimentary Pharmacology & Therapeutics. 2007; 26: 343-357.
  4. Malfertheiner P, Megraud F, O’Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuiper EJ, The European Helicobacter Study Group (EHSG). Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 2007; 56: 772-781.
  5. Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD. Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ 2010;340:c2096
  6. Chey W et al. American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection. Am J Gastroenterol 2007;102:1808–1825

Evidence levels:
A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.

Approved By

Improving Antimicrobial Prescribing Group & LAPC

Document history

LHP version 1.0

Related information

Appendix

Guideline for Treatment of Helicobacter pylori Infection in Adults in Primary Care

See main guideline for indications for testing
Test for H. pylori with either stool (H. pylori faecal antigen test) or endoscopic biopsy (CLO test)
Before testing, the patient should abstain from:

  • PPIs for 2 weeks
  • Bismuth and antibiotics for 4 weeks
  • H2-receptor antagonists for 48 hours
    to avoid false negative tests

Offer treatment to all patients newly diagnosed with H. pylori
Discuss treatment adherence with the person and emphasise its importance.
Do not re-test or re-treat for uninvestigated dyspepsia or functional dyspepsia
Leave at least 4 weeks before re-testing after eradication for PUD, gastric cancer or MALToma
For patients with PUD, Gastric cancer or MALToma who fail eradication therapy consider endoscopy for culture & susceptibility testing

 Preferred Option

Alternative (if penicillin allergy)

Alternative (if penicillin allergy AND prior clarithromycin exposure)

Notes

Lansoprazole capsules PO 30mg 12-hourly
AND 
Amoxicillin 1g
PO 12-hourly
AND EITHER
Clarithromycin 500mg
PO 12-hourly
OR
Metronidazole 400mg
PO 12-hourly

Lansoprazole capsules PO 30mg 12-hourly
AND 
Clarithromycin 250mg
PO 12-hourly
AND 
Metronidazole 400mg
PO 12-hourly

Lansoprazole capsules PO 30mg 12-hourly
AND 
Metronidazole 400mg PO 8-hourly
AND
Doxycycline PO 100mg 12-hourly
AND
Bismuth subsalicylate (Peptobismol) 525mg 6-hourly

Do not use clarithromycin or metronidazole if patient has history of use in the past year for any infection.

See NICE CG 184 Gastro-oesophageal reflux disease and dyspepsia in adults for choice of alternative PPI agents and dosing.

Duration of treatment
First line therapy: 7 days
MALToma: 14 days

For Second Line Therapy, Refer to Secondary Care guideline, NICE guideline or Refer to a Specialist

NICE CG 184 Gastro-oesophageal reflux disease and dyspepsia in adults