Helicobacter pylori antibiotic resistance dilemmas and key questions

Helicobacter pylori infection is thought to be the most common bacterial infection worldwide. Whilst the prevalence of H. pylori is decreasing rapidly in Europe, Australia and the USA, where on average 10-15% of the adult population are infected, it remains a significant problem in China, where serological studies in adults still show seroprevalence rates above 70%. Recent data from Auckland, New Zealand (2012), indicated high prevalence of infection in Maori (35%), Pacific peoples (31%) versus Europeans (8%).

H. pylori colonisation is associated with active gastritis but the vast majority (70%) of patients remain asymptomatic. H. pylori  remains on the surface and does not invade the epithelium of the gastric mucosa.  The bacteria are associated with peptic ulcers, gastric cancer and lymphoma. For an excellent review of upper GIT microbiota including Helicobacter and its associations with disease and health, see  Walker and Talley 2014.  

The primary treatment of H. pylori recommended by the Therapeutic Guidelines is a triple therapy combining a proton pump inhibitor (PPI) with amoxycillin and clarithromycin. Unfortunately resistance rates for H. pylori are climbing. Pre-treatment clarithromycin resistance is currently around 5% to 7%, though no recent reports from Australia (New Zealand 2012 rates of clarithromycin resistance were 16%, increasing from 7% in 1999). Previous clarithromycin or azithromycin exposure for other indications increases the likelihood of secondary resistance and treatment failure.  Regimens with metronidazole are no longer recommended due to resistance rates of over 50%.

When primary eradication therapy fails,  higher rates of clarithromycin resistance are seen and alternative antibiotics are needed. Usually the clarithromycin is replaced with levofloxacin or rifabutin. If these therapies fail a quadruple regimen containing bismuth, tetracycline and metronidazole can be used.

Resistance to H. pylori is a growing concern across the world. A decreased ability to treat H. pylori may result in increased rates of gastric cancer. A recent systematic review in the BMJ suggested that increasing the length of treatment, using probiotic supplements, using levofloxacin first line or using sequential treatments where one schedule is used after another might be better options for treatment.

Important questions remain that are highly relevant to patients and antimicrobial stewardship:

  1. What are the longterm effects of Helicobacter treatment on gastrointestinal microbiota,  microbiota-related diseases and colonisation or infection with antimicrobial resistant pathogens?
  2. Will future randomised trials confirm the suggested benefit of probiotic-supplemented Helicobacter treatments?
  3. Can we efficiently target patients who have antibiotic resistant  Helicobacter  infections to reduce unneeded exposure to fluoroquinolone antibiotics which are such important therapeutic agents for Gram negative infection?
  4. Can we reduce community macrolide (clarith/azithromycin) usage by taking a more critical approach to the broadspread usage of these agents in respiratory and sexual health medicine.  Such reductions may then reduce resistance in Helicobacter.
  5. What do current Australian Helicobacter antimicrobial susceptibility show and what prevalence trends are occurring, especially amongst Aboriginal and Torres Strait Islander groups?

Thanks Prof Marjorie Walker for your input on this posting! 

Other references

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One comment

  1. Reblogged this on Infectious Diseases and Microbiology postgraduate teaching and commented:

    Helicobacter macrolide and metronidazole resistance is driving potential usage of quinolones which then may conflict with multi-resistant Gram negative control strategies.

    Like

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