GASTROENTEROLOGY INFEC TIONS

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.

KEY PR AC TICE POINTS

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

www.bpac.org.nz July 2022 1

H. pylori infection increases the risk of of distal gastric cancers; Māori have both higher incidences of
gastric-related adverse effects H. pylori infection and distal gastric cancers, compared with
non-Māori in New Zealand.9
H. pylori is a gram-negative bacterium that is associated with
long-term gastric inflammation.1 Infection generally occurs in A risk-based approach is recommended for H.
childhood, although there is debate regarding the exact mode pylori testing in New Zealand
of transmission; oral-oral and faecal-oral are the most likely
routes, especially between mothers and infants.2 There are no recent New Zealand guidelines available
The majority of infected people will remain asymptomatic, on the management of H. pylori infection (or dyspepsia).
with H. pylori forming part of their normal gastric microflora.3 Regional advice differs and there is no published
However, in some people H. pylori infection can result in national expert consensus. We therefore present a
dyspepsia-like symptoms (which may be unresponsive to pragmatic approach based on international guidelines,
gastric acid suppression) or peptic ulcer disease.2 In some research, expert guidance and our knowledge of the
cases, early H. pylori infection can lead to the development general practice environment. We recommend that
of significant gastric malignancies later in life, e.g. gastric you also consult your local HealthPathways for specific
mucosa-associated lymphoid tissue lymphoma and non-cardia referral advice.
gastric adenocarcinomas.1, 2 , 4 People with H. pylori infection
have a lifetime risk of 10 – 20% for peptic ulcer disease and If people with H. pylori infection become symptomatic most will
1 – 2% for stomach cancer.5 In people taking non-steroidal present with dyspepsia-like symptoms such as pain, burning
anti-inflammatory drugs (NSAIDs), H. pylori infection can or discomfort in the upper abdomen, which can also be
also increase the risk of developing gastric bleeding or a associated with bloating, early satiety, nausea or vomiting.10 It is
gastroduodenal ulcer.2 not recommended to routinely test all patients with dyspepsia-
like symptoms for H. pylori nor prescribe empiric eradication
The prevalence of H. pylori in New Zealand is low by treatment for H. pylori without testing. Testing asymptomatic
global standards patients for H. pylori infection is not recommended but it may
The global prevalence of H. pylori infection is > 50%.2 Rates of be necessary in some cases, e.g. patients requiring long-term
infection are higher in Africa (79.1%), Asia (54.7%) and Latin NSAID treatment or patients with a family history of gastric
America and the Caribbean (63.4%), while a lower prevalence cancer.11, 12
is reported in Europe (47.0%) and Oceania (24.4%).6 Prevalence After considering red flags (see: “Red flags for people
has declined in many countries due to improvements in presenting with dyspepsia”), and modifiable factors such as
treatment and in standards of living, but there continues to be NSAID use, first-line management for patients with dyspepsia-
marked variation between, and within, countries.2 This is likely like symptoms is to offer lifestyle modification advice (see:
due to the different factors that influence rates of infection “Lifestyle modifications can help to manage dyspepsia
with H. pylori, including ethnicity, socioeconomic status and symptoms”) and trial a proton pump inhibitor (PPI) for a
younger age.2, 6 Rates remain higher in developing countries short duration, e.g. four weeks. If symptoms resolve, H. pylori
due to associations with increased transmission in areas with infection is unlikely to be the primary cause of the original
overcrowded living conditions, poor sanitation and unsafe symptoms.
drinking water.2, 6
While the prevalence of H. pylori infection in New Zealand Lifestyle modifications can help to manage dyspepsia
is low compared with many other developed countries, there is symptoms
variation between ethnic and regional groups.2, 6 A small 2013 Changes in diet and behaviour can help patients reduce
study in South Auckland found a significantly higher prevalence symptoms of dyspepsia. Examples include:10, 13–15
of H. pylori infection in Māori (34.9%), Pacific (29.6%), East Asian Reducing the size of meals
(23.8%) and Indian (19.2%) peoples, compared with New Avoiding large meals before bedtime
Zealand Europeans (7.7%); the overall prevalence of H. pylori Limiting intake of dietary fat and alcohol
across all ethnicities was 18.6%.7 A 2015 study showed that
Avoiding foods that trigger dyspepsia symptoms, e.g.
while H. pylori infections in New Zealand have decreased over
chilli or coffee
time, the difference in comparative risk between New Zealand
Reducing body weight
Europeans and Māori and Pacific peoples is increasing.5 This is
consistent with Māori and Pacific peoples experiencing higher Smoking cessation
rates of social deprivation and household overcrowding.8 Avoiding over-the-counter use of NSAIDs
Chronic H. pylori infection is associated with the development Stress management, e.g. cognitive behaviour therapy

2 July 2022 www.bpac.org.nz

If the patient’s symptoms do not improve after a PPI trial, Faecal antigen testing is recommended to
consider how likely it is that H. pylori will be present, based detect H. pylori infection
on factors including: Faecal antigen testing is the recommended non-invasive test
Geographic location – H. pylori prevalence is generally for H. pylori infection in New Zealand.21 Faecal antigen testing
higher in Northland and Auckland regions compared to can be used to diagnose active infection with H. pylori and,
the South Island5 if required, to confirm that eradication treatment has been
Ethnicity – the prevalence of H. pylori is higher in Māori, successful.1 This technique has a reported sensitivity of 94%
Pacific and Asian peoples (~19 – 35%) than in New and specificity of 97%.1 False negative results can occur if the
Zealand Europeans (≤ 7%)7 patient has been taking medicines that decrease the load of
Place of birth – prevalence of H. pylori is higher in people H. pylori in the stomach, e.g. antibiotics, or the contents of the
who were born in developing countries and people who stomach are less acidic, e.g. if a patient has been taking a PPI.1
immigrate retain a prevalence of H. pylori similar to their
country of origin16 Practice point: Patients should be advised not to take PPIs
within two weeks, or antibiotics or bismuth compounds (found
If H. pylori infection is considered likely, then faecal in some indigestion remedies) within four weeks prior to faecal
antigen testing is indicated (see: “Faecal antigen testing is antigen testing to prevent false negative results.2, 17
recommended to detect H. pylori infection”). In cases where
infection is considered unlikely, then continue PPI treatment Serum antibody testing (serology) for H. pylori has previously
and investigate/manage other potential causes. If none can been recommended as the most appropriate diagnostic test
be found or symptoms still do not resolve after alternative in New Zealand. However, with the improved availability
treatment options have been trialled, H. pylori testing can be and accuracy of faecal antigen tests, serology is no longer
considered or refer the patient to secondary care. preferred.21 Serology cannot distinguish between infection
that is past or current, and because antibody levels decrease
Red flags in patients presenting with dyspepsia slowly over 6 – 12 months or longer after eradication treatment,
A patient with any of the following factors has an it cannot be used as a test of treatment success.1, 19
increased risk of significant complications and may
require referral for endoscopy:17, 18 Carbon-13 urea breath testing is still regarded in the
Age ≥ 55 years at first presentation of new-onset literature as the gold standard for clinical diagnosis of H. pylori
dyspepsia (ten years earlier for Māori, Pacific or infection.1, 22 However, this test has limited availability in New
Asian patients*) Zealand due in part to the specialist laboratory equipment
and training required. Both the sensitivity and specificity for
Family history of gastric cancer with age of onset
carbon-13 urea breath testing is reported to be comparable to
< 50 years
faecal antigen testing.2, 22
Symptoms and signs of gastrointestinal bleeding,
such as haematemesis, anaemia or melaena Invasive testing is reserved for patients with dyspepsia
Iron-deficiency anaemia, without obvious cause, and red flag symptoms
e.g. menorrhagia Patients presenting with red flag symptoms may require
Difficulty swallowing more invasive testing, e.g. endoscopy, to identify or rule out
Palpable abdominal mass malignancy. It may be appropriate to prescribe a PPI and
request a faecal antigen test while patients are waiting for
Unexplained weight loss
endoscopy. Regional HealthPathways guidance suggests lower
* There is no New Zealand guideline that specifically states this thresholds for endoscopy referral in patients who present with
age, however, it is known that Māori are disproportionately dyspeptic symptoms and have a previous history of peptic
affected by gastric cancer, and at a younger age.9 The New
ulcer disease, family history of early onset gastric cancer, i.e.
Zealand Management of Dyspepsia and Heartburn guidelines,
relatives aged < 50 years, or significant ongoing symptoms
2004, are now out of date, but they recommended earlier
referral for endoscopy for Māori, Pacific or Asian patients as unresponsive to treatment. Endoscopy can also provide biopsy
gastric cancer presents ten years earlier in these groups.19 material for histology, rapid urease testing and cultures used
to detect or confirm H. pylori infection.2

www.bpac.org.nz July 2022 3

Eradication treatment for H. pylori infection Confirmation of H. pylori eradication is not usually
required
If H. pylori infection is confirmed, the patient should be
prescribed eradication treatment. In New Zealand, the first- Retesting of patients following a triple treatment regimen is
line option is a triple treatment regimen of a PPI (usually not required in most cases, e.g. if symptoms have resolved.10, 24
omeprazole, but other PPIs can be used), clarithromycin Faecal antigen testing is appropriate when considering second-
and either amoxicillin or metronidazole (Table 1).20 This line treatment in patients who have remained symptomatic
combination is consistent with international guidelines and following an initial triple treatment regimen, or to confirm
shown to be 70 – 85% effective.10, 23, 24 treatment success in patients with peptic ulcer complications
or other significant gastric conditions.2, 20, 24
Treatment duration is 7 – 14 days. Seven-days has previously It is generally recommended that follow-up testing occurs
been recommended as the standard duration for the triple no sooner than three months after treatment has ceased. 1
treatment regimen but recent international guidelines support Patients should be advised not to take PPIs within two weeks
a longer treatment period, e.g. 14 days in areas with a higher of testing, or antibiotics or bismuth compounds within four
prevalence of clarithromycin-resistant H. pylori, including New weeks of testing, to prevent false negative results.2, 17
Zealand.2, 25
When to consider second-line treatment
Consider previous antibiotic exposure. Research suggests
Expert advice: “Consideration should be given to not
any previous lifetime exposure to any macrolide antibiotic*
proceeding with further treatment if risks outweigh
(due to cross-resistance) or metronidazole increases the risk
benefits, particularly if it seems likely that the
for antibiotic resistance and H. pylori treatment failure.26, 27
symptoms are unrelated to the infection”
Therefore, a history of exposure to these medicines in patients
with confirmed H. pylori infection should influence treatment If first-line treatment for H. pylori is unsuccessful,
decisions (see Table 1 for recommendations). In practice, it can consider the risks and benefits of escalating treatment.
be difficult to establish previous use of specific antibiotics from There may not always be a strong correlation between
patient history or clinical notes, especially if there has been dyspepsia and a diagnosis of H. pylori and good
considerable period since exposure. results with treatment. In some patients, escalation
* Commonly used macrolides include erythromycin, roxithromycin, of the PPI dose does not reduce symptoms and there
azithromycin and clarithromycin 20 may need to be more emphasis on lifestyle changes
and stress management. In addition, patients who
For further information on dosing, see: www.nzf.org.nz/ experienced adverse effects associated with H. pylori
nzf_732 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

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

First-line treatment: Omeprazole, 20 mg twice daily; and

7 – 14 days 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

4 July 2022 www.bpac.org.nz

Recurrence of H. pylori following treatment can be divided The second-line regimen. International guidelines vary in their
into recrudescence and reinfection.30 Recrudescence is the recommendations for second-line treatment regimens; these
temporary suppression and then reemergence, rather than are often based on evidence specific to local populations and
successful treatment of the original H. pylori strain.30 This may may be influenced by medicine availability.31 In New Zealand,
be related to ineffective treatment regimens and reflects most the second-line option is a two-week quadruple regimen
incidences of H. pylori recurrence.30 Reinfection with a new H. of a PPI, e.g. omeprazole, tripotassium dicitratobismuthate
pylori organism after successful treatment is rare in developed (bismuth), tetracycline and metronidazole (Table 2). 20
countries and likely to involve re-exposure via close contacts Doxycycline is not recommended as an alternative tetracycline
who have not received eradication treatment.30 as it results in lower eradication rates for H. pylori.7
If testing confirms that H. pylori is still present three N.B. Levofloxacin is included in some second or third-
months or more since treatment, and the patient remains line eradication regimens in international guidance. In New
symptomatic, a second course of treatment can be considered, Zealand it is an unapproved, unfunded medicine, with limited
using a different regimen. Alternatively, referral for endoscopy availability. If levofloxacin can be procured (under Section 29),
may be considered.10, 20, 24 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: Omeprazole, 20 mg twice daily; and

14 days 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.

H. pylori antibiotic resistance is rising

Globally, there are concerns regarding increasing for increases in H. pylori antibiotic resistance include
resistance of H. pylori to standard antibiotic treatments.25, 32 inappropriate prescribing of antibiotics used in eradication
A recent meta-analysis of data from 65 countries found regimens, lack of adherence to medicine regimens, cross
rates of both primary and secondary resistance of H. pylori resistance between other previously prescribed macrolide
to clarithromycin, metronidazole and levofloxacin, to be antibiotics, low-grade antibiotic exposure through
> 15%.32 A 2013 New Zealand study found resistance consumption of food products from treated livestock and
to clarithromycin had doubled since 1999.7 Rates of immigration from areas of historically high prevalence
clarithromycin resistance varied with ethnicity; no of antibiotic resistant H. pylori.25, 33, 34 This highlights the
resistance was reported in New Zealand Europeans while importance of assessing a patient’s antibiotic history, if
a rate of 25% was reported in Māori.7 Potential causes possible, before deciding on what medicines to prescribe.

www.bpac.org.nz July 2022 5

 Clinician’s Notepad: H. pylori
Patient presenting with dyspepsia-like symptoms In patients with a confirmed H. pylori infection
Consider whether red flags are present that Prescribe first-line triple treatment (eradication)
may indicate the need for referral for further regimen for 7 – 14 days, consisting of a PPI (e.g.
investigation: omeprazole, 20 mg twice daily); and clarithromycin
Age ≥ 55 years at first presentation of new- (500 mg twice daily); and amoxicillin (1,000 mg
onset dyspepsia (ten years earlier for Māori, twice daily) or metronidazole (400 mg twice daily)
Pacific or Asian patients) N.B. Consider previous antibiotic exposure before
Family history of gastric cancer with age of prescribing. If prior exposure to:
onset < 50 years – Any macrolide antibiotic – prescribe omeprazole
Symptoms and signs of gastrointestinal + amoxicillin + metronidazole (dosing as above)
bleeding, such as haematemesis, anaemia or – Metronidazole – prescribe omeprazole +
melaena amoxicillin + clarithromycin (dosing as above)
– Both macrolide antibiotics and metronidazole –
Iron-deficiency anaemia, without obvious cause,
discuss options with a gastroenterologist, clinical
e.g. menorrhagia
microbiologist or infectious disease specialist
Difficulty swallowing
Confirmation of eradication is not usually required if
Palpable abdominal mass
symptoms resolve
Unexplained weight loss
If symptoms remain following first-line treatment:
Recommend lifestyle changes, e.g. reducing meal Re-test for H. pylori infection three months later
size, avoiding large meals before bedtime, limiting If the test is still positive, consider whether the
alcohol intake, avoiding trigger foods, weight loss potential benefits of further antibiotic treatment
Trial a proton pump inhibitor (PPI), e.g. 20 mg outweigh the risks
omeprazole once daily, for four to eight weeks If a decision is made to provide further antibiotic
treatment, prescribe a 14 day second-line regimen
If symptoms do not improve after a PPI trial including a PPI (e.g. omeprazole, 20 mg twice daily);
Consider the risk of H. pylori infection. Factors and tripotassium dicitratobismuthate (bismuth; 120
influencing risk include geographic location (the mg four times daily); and tetracycline (500 mg four
prevalence is generally higher in Northland and times daily); and metronidazole (400 mg three times
Auckland regions), being of Māori, Pacific or Asian daily)
ethnicity, or having been born in a country with high
rates of H. pylori infection If symptoms remain following second-line treatment,
If patients are considered to be at: or if second-line treatment is not undertaken for
– High-risk of H. pylori infection, request faecal any reason despite continuing symptoms/infection,
antigen testing (stop PPI for two weeks before the consider referral to a gastroenterologist.
test)
– 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 or with continued PPI use, H. pylori
testing can be considered, or refer patient to
secondary care.

6 July 2022 www.bpac.org.nz

Acknowledgement: Thank you to Associate Professor 19. New Zealand Guidelines Group (NZGG). Management of dyspepsia and
heartburn. Evidence-based best practice guideline summary. 2004. Available
Alan Fraser, Consultant Gastroenterologist, Auckland and
from: https://www.health.govt.nz/system/files/documents/publications/
Honorary Associate Professor of Medicine, University of dyspepsia_summary.pdf (Accessed Jul, 2022).
Auckland, for expert review of this article. 20. New Zealand Formulary (NZF). NZF v121. 2022. Available from: https://www.
N.B. Expert reviewers do not write the articles and are not responsible for nzf.org.nz/nzf_1 (Accessed Jul, 2022).
the final content. bpacnz retains editorial oversight of all content. 21. Upton A. Discontinuation of Helicobacter pylori serology. 2020. Available from:
https://fl-healthscope-media.s3.amazonaws.com/lab-sites/uploads/2020/07/
H.-Pylori-Service-Update-July-2020.docx.pdf (Accessed Jul, 2022).
22. Patel SK, Pratap CB, Jain AK, et al. Diagnosis of Helicobacter pylori: what should
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