H. pylori: who to test and how to treat

Helicobacter pylori infection increases the risk of peptic ulcer disease and gastric cancer due to long-term inflammation and atrophy of the stomach mucosa. Deciding who to test for infection with H. pylori, and what treatment regimen to prescribe, is influenced by several factors, including geographic location and ethnicity.

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Published: 20 July 2022


Key practice points:

  • The overall prevalence of H. pylori is low in New Zealand compared to the rest of the world; infection is more likely in Māori, Pacific and Asian people compared with New Zealand Europeans
  • Most people with H. pylori infection will remain asymptomatic; if symptoms do occur, patients are most likely to present with dyspepsia-like symptoms
  • In patients who present with new-onset dyspepsia-like symptoms, check for red flags (e.g. symptoms and signs of gastrointestinal bleeding), advise lifestyle modification and prescribe a proton pump inhibitor (PPI) for a short trial period, e.g. four weeks
    • If there is no improvement in symptoms, reiterate the importance of lifestyle modification and consider the patient’s risk for H. pylori infection
  • The decision to test for H. pylori in symptomatic people depends on a risk assessment based on multiple factors, including the patient’s ethnicity, country of birth, regional infection risk and severity of symptoms
  • For patients who are at:
    • High risk of H. pylori infection – consider faecal antigen testing. Patients will need to have stopped taking a PPI two weeks before testing.
    • Low risk of H. pylori infection – continue PPI treatment and investigate other potential causes. If none can be found or symptoms still do not resolve after alternative treatment options have been trialed, H. pylori testing can be considered, or refer patient to secondary care.
  • Faecal antigen testing is the preferred investigation for H. pylori; serology testing is generally not recommended because it does not differentiate between current or past infection
  • If infection with H. pylori is confirmed, first-line treatment is a 7 – 14-day course of omeprazole, clarithromycin and amoxicillin (or metronidazole)
  • If first-line treatment is unsuccessful, consider if the risks of further antibiotic treatment outweigh the benefits, particularly if it seems likely that the symptoms are unrelated to the infection
  • If the patient is still symptomatic after three months and testing confirms that H. pylori is still present, the second-line treatment regimen includes omeprazole, metronidazole, colloidal bismuth and tetracycline

H. pylori is a gram-negative bacterium that is associated with long-term gastric inflammation.1 Infection generally occurs in childhood, although there is debate regarding the exact mode of transmission; oral-oral and faecal-oral are the most likely routes, especially between mothers and infants.2

The majority of infected people will remain asymptomatic, with H. pylori forming part of their normal gastric microflora.3 However, in some people H. pylori infection can result in dyspepsia-like symptoms (which may be unresponsive to gastric acid suppression) or peptic ulcer disease.2 In some cases, early H. pylori infection can lead to the development of significant gastric malignancies later in life, e.g. gastric mucosa-associated lymphoid tissue lymphoma and non-cardia gastric adenocarcinomas.1,2,4 People with H. pylori infection have a lifetime risk of 10 – 20% for peptic ulcer disease and 1 – 2% for stomach cancer.5 In people taking non-steroidal anti-inflammatory drugs (NSAIDs), H. pylori infection can also increase the risk of developing gastric bleeding or a gastroduodenal ulcer.2

The prevalence of H. pylori in New Zealand is low by global standards

The global prevalence of H. pylori infection is > 50%.2 Rates of infection are higher in Africa (79.1%), Asia (54.7%) and Latin America and the Caribbean (63.4%), while a lower prevalence is reported in Europe (47.0%) and Oceania (24.4%).6 Prevalence has declined in many countries due to improvements in treatment and in standards of living, but there continues to be marked variation between, and within, countries.2 This is likely due to the different factors that influence rates of infection with H. pylori, including ethnicity, socioeconomic status and younger age.2, 6 Rates remain higher in developing countries due to associations with increased transmission in areas with overcrowded living conditions, poor sanitation and unsafe drinking water.2, 6

While the prevalence of H. pylori infection in New Zealand is low compared with many other developed countries, there is variation between ethnic and regional groups.2, 6 A small 2013 study in South Auckland found a significantly higher prevalence of H. pylori infection in Māori (34.9%), Pacific (29.6%), East Asian (23.8%) and Indian (19.2%) peoples, compared with New Zealand Europeans (7.7%); the overall prevalence of H. pylori across all ethnicities was 18.6%.7 A 2015 study showed that while H. pylori infections in New Zealand have decreased over time, the difference in comparative risk between New Zealand Europeans and Māori and Pacific peoples is increasing.5 This is consistent with Māori and Pacific peoples experiencing higher rates of social deprivation and household overcrowding.8 Chronic H. pylori infection is associated with the development of distal gastric cancers; Māori have both higher incidences of H. pylori infection and distal gastric cancers, compared with non-Māori in New Zealand.9

There are no recent New Zealand guidelines available on the management of H. pylori infection (or dyspepsia). Regional advice differs and there is no published national expert consensus. We therefore present a pragmatic approach based on international guidelines, research, expert guidance and our knowledge of the general practice environment. We recommend that you also consult your local HealthPathways for specific referral advice.

If people with H. pylori infection become symptomatic most will present with dyspepsia-like symptoms such as pain, burning or discomfort in the upper abdomen, which can also be associated with bloating, early satiety, nausea or vomiting.10 It is not recommended to routinely test all patients with dyspepsia-like symptoms for H. pylori nor prescribe empiric eradication treatment for H. pylori without testing. Testing asymptomatic patients for H. pylori infection is not recommended but it may be necessary in some cases, e.g. patients requiring long-term NSAID treatment or patients with a family history of gastric cancer.11, 12

After considering red flags (see: “Red flags for people presenting with dyspepsia”), and modifiable factors such as NSAID use, first-line management for patients with dyspepsia-like symptoms is to offer lifestyle modification advice (see: “Lifestyle modifications can help to manage dyspepsia symptoms”) and trial a proton pump inhibitor (PPI) for a short duration, e.g. four weeks. If symptoms resolve, H. pylori infection is unlikely to be the primary cause of the original symptoms.

Lifestyle modifications can help to manage dyspepsia symptoms

Changes in diet and behaviour can help patients reduce symptoms of dyspepsia. Examples include:10, 13–15

  • Reducing the size of meals
  • Avoiding large meals before bedtime
  • Limiting intake of dietary fat and alcohol
  • Avoiding foods that trigger dyspepsia symptoms, e.g. chilli or coffee
  • Reducing body weight
  • Smoking cessation
  • Avoiding over-the-counter use of NSAIDs
  • Stress management, e.g. cognitive behaviour therapy

If the patient’s symptoms do not improve after a PPI trial, consider how likely it is that H. pylori will be present, based on factors including:

  • Geographic location – H. pylori prevalence is generally higher in Northland and Auckland regions compared to the South Island5
  • Ethnicity – the prevalence of H. pylori is higher in Māori, Pacific and Asian peoples (~19 – 35%) than in New Zealand Europeans (≤ 7%)7
  • Place of birth – prevalence of H. pylori is higher in people who were born in developing countries and people who immigrate retain a prevalence of H. pylori similar to their country of origin16

If H. pylori infection is considered likely, then faecal antigen testing is indicated (see: “Faecal antigen testing is recommended to detect H. pylori infection”). In cases where infection is considered unlikely, then continue PPI treatment and investigate/manage other potential causes. If none can be found or symptoms still do not resolve after alternative treatment options have been trialled, H. pylori testing can be considered or refer the patient to secondary care.

Red flags in patients presenting with dyspepsia

A patient with any of the following factors has an increased risk of significant complications and may require referral for endoscopy:17, 18

  • Age ≥ 55 years at first presentation of new-onset dyspepsia (ten years earlier for Māori, Pacific or Asian patients*)
  • Family history of gastric cancer with age of onset < 50 years
  • Symptoms and signs of gastrointestinal bleeding, such as haematemesis, anaemia or melaena
  • Iron-deficiency anaemia, without obvious cause, e.g. menorrhagia
  • Difficulty swallowing
  • Palpable abdominal mass
  • Unexplained weight loss

*There is no New Zealand guideline that specifically states this age, however, it is known that Māori are disproportionately affected by gastric cancer, and at a younger age.9 The New Zealand Management of Dyspepsia and Heartburn guidelines, 2004, are now out of date, but they recommended earlier referral for endoscopy for Māori, Pacific or Asian patients as gastric cancer presents ten years earlier in these groups.19

Faecal antigen testing is the recommended non-invasive test for H. pylori infection in New Zealand.21 Faecal antigen testing can be used to diagnose active infection with H. pylori and, if required, to confirm that eradication treatment has been successful.1 This technique has a reported sensitivity of 94% and specificity of 97%.1 False negative results can occur if the patient has been taking medicines that decrease the load of H. pylori in the stomach, e.g. antibiotics, or the contents of the stomach are less acidic, e.g. if a patient has been taking a PPI.1

Practice point: Patients should be advised not to take PPIs within two weeks, or antibiotics or bismuth compounds (found in some indigestion remedies) within four weeks prior to faecal antigen testing to prevent false negative results.2, 17

Serum antibody testing (serology) for H. pylori has previously been recommended as the most appropriate diagnostic test in New Zealand. However, with the improved availability and accuracy of faecal antigen tests, serology is no longer preferred.21 Serology cannot distinguish between infection that is past or current, and because antibody levels decrease slowly over 6 – 12 months or longer after eradication treatment, it cannot be used as a test of treatment success.1, 19

Carbon-13 urea breath testing is still regarded in the literature as the gold standard for clinical diagnosis of H. pylori infection.1, 22 However, this test has limited availability in New Zealand due in part to the specialist laboratory equipment and training required. Both the sensitivity and specificity for carbon-13 urea breath testing is reported to be comparable to faecal antigen testing.2, 22

Invasive testing is reserved for patients with dyspepsia and red flag symptoms

Patients presenting with red flag symptoms may require more invasive testing, e.g. endoscopy, to identify or rule out malignancy. It may be appropriate to prescribe a PPI and request a faecal antigen test while patients are waiting for endoscopy. Regional HealthPathways guidance suggests lower thresholds for endoscopy referral in patients who present with dyspeptic symptoms and have a previous history of peptic ulcer disease, family history of early onset gastric cancer, i.e. relatives aged < 50 years, or significant ongoing symptoms unresponsive to treatment. Endoscopy can also provide biopsy material for histology, rapid urease testing and cultures used to detect or confirm H. pylori infection.2

If H. pylori infection is confirmed, the patient should be prescribed eradication treatment. In New Zealand, the first-line option is a triple treatment regimen of a PPI (usually omeprazole, but other PPIs can be used), clarithromycin and either amoxicillin or metronidazole (Table 1).20 This combination is consistent with international guidelines and shown to be 70 – 85% effective.10, 23, 24

Treatment duration is 7 – 14 days. Seven-days has previously been recommended as the standard duration for the triple treatment regimen but recent international guidelines support a longer treatment period, e.g. 14 days in areas with a higher prevalence of clarithromycin-resistant H. pylori, including New Zealand.2, 25

Consider previous antibiotic exposure. Research suggests any previous lifetime exposure to any macrolide antibiotic* (due to cross-resistance) or metronidazole increases the risk for antibiotic resistance and H. pylori treatment failure.26, 27 Therefore, a history of exposure to these medicines in patients with confirmed H. pylori infection should influence treatment decisions (see Table 1 for recommendations). In practice, it can be difficult to establish previous use of specific antibiotics from patient history or clinical notes, especially if there has been considerable period since exposure.

*Commonly used macrolides include erythromycin, roxithromycin, azithromycin and clarithromycin 20

For further information on dosing, see: www.nzf.org.nz/nzf_732


Table 1. First-line H. pylori eradication dosing regimen.10, 20, 24

First-line treatment:
7 – 14 days

  • Omeprazole, 20 mg twice daily; and
  • Clarithromycin, 500 mg twice daily; and
  • Amoxicillin, 1,000 mg twice daily; or Metronidazole, 400 mg twice daily

If previous exposure to:

Recommendation:

  • Any macrolide antibiotic
  • Prescribe omeprazole + amoxicillin + metronidazole (dosing as above)
  • Metronidazole
  • Prescribe omeprazole + amoxicillin + clarithromycin (dosing as above)
  • Both macrolide antibiotics and metronidazole
  • Discuss options with a gastroenterologist, clinical microbiologist or infectious disease specialist

Confirmation of H. pylori eradication is not usually required

Retesting of patients following a triple treatment regimen is not required in most cases, e.g. if symptoms have resolved.10, 24 Faecal antigen testing is appropriate when considering second-line treatment in patients who have remained symptomatic following an initial triple treatment regimen, or to confirm treatment success in patients with peptic ulcer complications or other significant gastric conditions.2, 20, 24

It is generally recommended that follow-up testing occurs no sooner than three months after treatment has ceased.1 Patients should be advised not to take PPIs within two weeks of testing, or antibiotics or bismuth compounds within four weeks of testing, to prevent false negative results.2, 17

When to consider second-line treatment

Expert advice: “Consideration should be given to not proceeding with further treatment if risks outweigh benefits, particularly if it seems likely that the symptoms are unrelated to the infection

If first-line treatment for H. pylori is unsuccessful, consider the risks and benefits of escalating treatment. There may not always be a strong correlation between dyspepsia and a diagnosis of H. pylori and good results with treatment. In some patients, escalation of the PPI dose does not reduce symptoms and there may need to be more emphasis on lifestyle changes and stress management. In addition, patients who experienced adverse effects associated with H. pylori eradication treatment may be reluctant to consider further eradication treatment and, on top of already complicated treatment regimens, are at increased risk of non-adherence.29

Recurrence of H. pylori following treatment can be divided into recrudescence and reinfection.30 Recrudescence is the temporary suppression and then reemergence, rather than successful treatment of the original H. pylori strain.30 This may be related to ineffective treatment regimens and reflects most incidences of H. pylori recurrence.30 Reinfection with a new H. pylori organism after successful treatment is rare in developed countries and likely to involve re-exposure via close contacts who have not received eradication treatment.30

If testing confirms that H. pylori is still present three months or more since treatment, and the patient remains symptomatic, a second course of treatment can be considered, using a different regimen. Alternatively, referral for endoscopy may be considered.10, 20, 24

The second-line regimen. International guidelines vary in their recommendations for second-line treatment regimens; these are often based on evidence specific to local populations and may be influenced by medicine availability.31 In New Zealand, the second-line option is a two-week quadruple regimen of a PPI, e.g. omeprazole, tripotassium dicitratobismuthate (bismuth), tetracycline and metronidazole (Table 2).20 Doxycycline is not recommended as an alternative tetracycline as it results in lower eradication rates for H. pylori.7

N.B. Levofloxacin is included in some second or third-line eradication regimens in international guidance. In New Zealand it is an unapproved, not funded medicine, with limited availability. If levofloxacin can be procured (under Section 29), it can be combined with omeprazole and amoxicillin in a 14-day regimen.20


Table 2. Second-line H. pylori eradication dosing regimen.10, 20, 24

Second-line treatment:
14 days

  • Omeprazole, 20 mg twice daily; and
  • Tripotassium dicitratobismuthate (bismuth)*, 120 mg four times daily; and
  • Tetracycline, 500 mg four times daily; and
  • Metronidazole, 400 mg three times daily

* Tripotassium dicitratobismuthate (colloidal bismuth sub citrate; funded) is an unapproved medicine, supplied under Section 29

Tetracycline hydrochloride is funded with Special Authority approval when prescribed as part of the H. pylori quadruple treatment regimen and first-line treatment has not been successful. It is an unapproved medicine, supplied under Section 29.


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Acknowledgement

Thank you to Associate Professor Alan Fraser, Consultant Gastroenterologist, Auckland and Honorary Associate Professor of Medicine, University of Auckland, for expert review of this article.

N.B. Expert reviewers do not write the articles and are not responsible for the final content. bpacnz retains editorial oversight of all content.


Ben Gray 29 Jul 2022 11:41

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