eradication therapy (triple therapy for H. pylori)

Last edited 06/2021 and last reviewed 09/2022

Helicobacter pylori: triple therapy (1,2):

Eradication

First-line treatment in adults

• offer people who test positive for H pylori a 7-day, twice-daily course of treatment with:
  • a PPI (see table in notes) and
  • amoxicillin 1g and
  • either clarithromycin 500mg or metronidazole 400mg
    
    
• offer people who are allergic to penicillin a 7-day, twice-daily course of treatment with:
  • a PPI (see table in notes) and
  • clarithromycin 250mg and
  • metronidazole 400mg
    
    
• offer people who are allergic to penicillin and who have had previous exposure to clarithromycin a 7-day, twice-daily course of treatment with:
  • a PPI (see table in notes) and
  • bismuth and
  • metronidazole 400mg and
  • tetracycline 500mg

Second-line treatment in adults

• offer people who still have symptoms after first-line eradication treatment a 7-day, twice-daily course of treatment with:
  • a PPI (see table in notes) and
  • amoxicillin 1g bd and
  • either clarithromycin 500mg bd or metronidazole 400mg bd (whichever was not used first-line)
    
    
• offer people who have had previous exposure to clarithromycin and metronidazole a 7-day, twice-daily course of treatment with:
  • a PPI (see table) and
  • amoxicillin 1g and
  • a quinolone or tetracycline 500mg
    
    
• offer people who are allergic to penicillin (and who have not had previous exposure to a quinolone) a 7-day, twice-daily course of treatment with:
  • a PPI (see table) and
  • metronidazole 400mg and
  • levofloxacin 250mg
    
    
• offer people who are allergic to penicillin and who have had previous exposure to a quinolone:
  • a PPI (see table) and
  • bismuth and
  • metronidazole 400mg and
  • tetracycline 500mg

Seek advice from a gastroenterologist if eradication of H pylori is not successful with second-line treatment

Notes (2):

• there is evidence that the addition of bovine lactoferrin to triple therapy led to an increase in Helicobacter pylori eradication (3)
  • a more recent meta-analysis concluded that "...supplementation with probiotics could be effective in increasing eradication rates of anti-H. pylori therapy, and could be considered helpful for patients with eradication failure. Furthermore, probiotics show a positive impact on H. pylori therapy-related side effects.." (4)
• quadruple therapy for H. pylori
  • a meta-analysis revealed that quadruple therapy appeared to be more effective than triple therapies for eradicating single-drug resistant H. pylori infection (5)
    • the study authors observed that resistance to metronidazole or clarithromycin could be overcome to a great extent with quadruple therapies given for 5 or more days, especially those containing metronidazole and clarithromycin concomitantly

• PPI doses for H pylori eradication therapy (1)

  PPI	Dose (twice daily)
  Esomeprazole	20mg
  Lansoprazole	30mg
  Omeprazole	20-40mg
  Pantoprazole	40mg
  Rabeprazole	20mg

  
  
  
• use of quinaolones - See MHRA advice for restrictions and precautions for using fluoroquinolone antibiotics due to very rare reports of disabling and potentially long-lasting or irreversible side effects affecting musculoskeletal and nervous systems. Warnings include: stopping treatment at first signs of a serious adverse reaction (such as tendonitis), prescribing with special caution in people over 60 years and avoiding coadministration with a corticosteroid (March 2019)
  
  
• key points (6):
  • always test for H.pylori before giving antibiotics. Treat all positives, if known DU (duodenal ulcer), GU (gastric ulcer), or low-grade MALToma. NNT in non-ulcer dyspepsia: 14.4
  • do not offer eradication for GORD
  • do not use clarithromycin, metronidazole or quinolone if used in the past year for any infection
  • penicillin allergy:
    • use PPI PLUS clarithromycin PLUS metronidazole
    • if previous clarithromycin, use PPI PLUS bismuth salt PLUS metronidazole PLUS tetracycline hydrochloride
  • relapse and no penicillin allergy use PPI PLUS amoxicillin PLUS clarithromycin or metronidazole (whichever was not used first line)
  • relapse and previous metronidazole and clarithromycin: use PPI PLUS amoxicillin PLUS either tetracycline OR levofloxacin (if tetracycline not tolerated)
  • relapse and penicillin allergy (no exposure to quinolone): use PPI PLUS metronidazole PLUS levofloxacin
  • relapse and penicillin allergy (with exposure to quinolone): use PPI PLUS bismuth salt PLUS metronidazole PLUS tetracycline
  • retest for H. pylori:
    • post DU/GU, or relapse after second-line therapy, using Urea Breath Test or stool antigen tests, consider referral for endoscopy and culture

Reference:

• (1) NICE (October 2019).Dyspepsia and gastro-oesophageal reflux disease - Investigation and management of dyspepsia, symptoms suggestive of gastro-oesophageal reflux disease, or both
• (2) Alahdab YO, Kalayci C.Helicobacter pylori: management in 2013. World J Gastroenterol. 2014 May 14;20(18):5302-7.
• (3) Di Mario F et al. Bovine lactoferrin for Helicobacter pylori eradication: an open, randomized, multicentre study. Aliment Pharmacol Ther 2006;23:1235-40.
• (4) Tong JL et al. Meta-analysis: the effect of supplementation with probiotics on eradication rates and adverse events during Helicobacter pylori eradication therapy. Aliment Pharmacol Ther. 2007 Jan 15;25(2):155-68.
• (5) Fischbach L, Evans EL. Meta-analysis: the effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapies for Helicobacter pylori.Aliment Pharmacol Ther. 2007 Aug 1;26(3):343-57
• (6) Public Health England (June 2021). Managing common infections: guidance for primary care