Helicobacter pylori infection

Introduction

Australia has a history of important medical discoveries that have changed the way disease is treated worldwide.

Amongst the most well-known are Howard Walter Florey’s role in the development of penicillin, and the invention of the bionic ear and the cervical cancer vaccines.

In 1982, Robin Warren and Barry Marshall discovered that the bacterium Helicobacter pylori was implicated in chronic gastritis, and the cause of most gastric and duodenal ulcers.

The two Australians were subsequently awarded the 2005 Nobel Prize in Physiology or Medicine.¹

What is H. pylori?

H. Pylori is a gram negative bacterium that colonises the stomach.²

Infection with H. pylori induces a persistent immune response, resulting in inflammation of the stomach lining and increases in gastric acid release.^2,3

There is evidence to suggest that the bacterium has been associated with humans for over 60,000 years.⁴

H. Pylori infection has a prevalence amongst the Australian population of approximately 30%.⁵

Infection is believed to occur during childhood; however, the exact mechanism of transmission is unknown. Ingestion appears to be the most likely means of acquisition.⁶

Transmission occurs from person to person within the family setting and is more common in low socioeconomic populations.

Levels of hygiene, number of siblings and household crowding are some of the more common predictors of infection during childhood.⁶

Because H. pylori has numerous adaptations to prevent immune detection, infection is lifelong unless treated.^2,3

Symptoms and consequences

All people with H. pylori infection develop chronic gastritis, yet it is asymptomatic in most cases.⁵

Infection is clinically significant due to its strong association with peptic ulcer disease. More than 90% of duodenal ulcers and 60% of gastric ulcers can be attributed to infection with H. pylori.^2,7

Individuals with H. pylori have a lifetime risk of peptic ulcer disease of up to 20%.⁵

H. pylori-associated peptic ulcer disease follows a chronic relapsing course with periodic episodes of pain and abdominal discomfort, which may be accompanied by nausea, vomiting and heartburn.⁵ This also carries an increased risk of complications such as gastric bleeding.⁵

Relation to gastric cancer

The most significant consequence of H. pylori infection is gastric cancer.

The individual lifetime risk of a person with H. pylori developing gastric adenocarcinoma is 1–2%.⁶

Treatment of H. pylori is strongly recommended in infected individuals who have other risk factors, such as a family history of gastric cancer, migrants from high risk areas and older people.⁵

Treatment and maintenance therapy

A ‘test and treat’ strategy is generally adopted using non-invasive diagnostic tests such as the radioactive carbon urea breath test (UBT) in any patients with suspected infection.⁶

The decision to then treat H. pylori should be individualised to a person’s circumstances and risk profile.^5,6

Proton pump inhibitor (PPI) triple therapy is the most common treatment used worldwide, and is effective in preventing the recurrence of gastric and duodenal ulcers.^2,7

The choice of medications used in eradication therapy is based on resistance patterns within each individual country. In Australia, first-line therapy is:

Esomeprazole 20mg orally, twice daily for 7 days
PLUS
Amoxicillin 1g orally, twice daily for 7 days
PLUS
Clarithromycin 500mg orally, twice daily for 7 days

For patients hypersensitive to penicillins, use:

A proton pump inhibitor orally, twice daily for 7 days
PLUS
Metronidazole 400mg orally, twice daily for 7 days
PLUS
Clarithromycin 500mg orally, twice daily for 7 days

First-line therapy has a successful eradication rate of 85 to 90% in clinical trials, while the metronidazole regimen has an eradication rate of approximately 80%.⁵

Rates are lower in the primary care setting, primarily due to incomplete adherence.²

Maintenance acid suppression is usually unnecessary following successful H. pylori eradication; however, it may be considered for individuals who are prescribed NSAIDs on an ongoing basis.⁵

Resistance

Antibiotic resistance continues to be an important consideration in the treatment of H. pylori worldwide.

In Australia, clarithromycin resistance appears to be low (6–8%) while metronidazole resistance remains very high 45–50%.⁶

A decline in the efficacy of triple therapy has been observed over the past decade and has been attributed to antibiotic resistance.⁸

Alternative treatment regimens have been studied to address issues with resistance, most commonly a sequential therapy comprising an induction phase of amoxicillin and a PPI for five days, followed by five days with a PPI, clarithromycin and metronidazole.⁸ However, this regimen has not been shown to offer any benefits over standard triple therapy.

Consideration for pharmacists

Compliance is the major determinant of eradication effectiveness with all H. pylori treatment regimens.⁵

Pharmacists should stress the importance of compliance, in particular completion of the week-long course.

Adverse effects, including taste disturbances, nausea and loose stools, contribute to non-compliance, occurring in up to 20% of patients.^2,5

Advance warning of these effects should form part of patient counselling.

Drug interactions — particularly with clarithromycin — should also be considered in patients taking other medications. For example, some statins should be temporarily ceased during H. pylori eradication treatment.⁹

Patients should also be advised to stay off PPIs for at least two weeks prior to a UBT, in order to avoid false positives.¹⁰

Conclusion

Pharmacists play an important role in promoting compliance with H. pylori treatment regimens, which will potentially improve eradication rates and minimise antibiotic resistance.

Nick Wilson, Resource Development Pharmacist, The Pharmacy Guild of Australia

References

1. The Nobel Prize in Physiology or Medicine 2005 [press release]. Nobel Media AB 20192005.
2. Yaxley B, Chakravarty B. Helicobater pylori eradication – an update on the latest therapies. Australian Family Physician. 2014;43(5):301–5.
3. Gastroenterology Society of Australia. Information about Helicobacter Pylori (H.pylori). Digestive Health Foundation; 2010.
4. Moodley Y, Linz B, Bond RP, Nieuwoudt M, Soodyall H, Schlebusch CM, et al. Age of the Association between Helicobacter pylori and Man (Age of Helicobacter pylori). PLoS Pathogens. 2012;8(5)
5. Gastrointestinal Expert Group. Helicobacter pylori infection In: eTG Complete [Internet] Melbourne. Therapeutic Guidelines Ltd. 2019. Available at www.tg.org.au [Accessed 04 Feb 2019].
6. Mitchell H, Katelaris P. Epidemiology, clinical impacts and current clinical management of Helicobacter pylori infection. Med J Aust. 2016;204(10):376–80.
7. Ford AC, Gurusamy KS, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori‐positive people. Cochrane Database of Systematic Reviews. 2016(4).
8. Nyssen OP, McNicholl AG, Megraud F, Savarino V, Oderda G, Fallone CA, et al. Sequential versus standard triple first‐line therapy for Helicobacter pylori eradication. Cochrane Database of Systematic Reviews. 2016(6).
9. Australian Medicines Handbook [Internet] Adelaide. Australian Medicines Handbook Pty Ltd; 2019. Available at: amhonline.amh.net.au [Accessed 04 Feb 2019].
10. Dore, M. P., Pes, G. M., Bassotti, G., & Usai-Satta, P. (2016). Dyspepsia: When and How to Test for Helicobacter pylori Infection. Gastroenterology research and practice, 2016, 8463614.