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1
NICE. Dyspepsia and gastro-oesophageal reflux disease: Investigation and management of dyspepsia, symptoms suggestive of gastro-oesophageal reflux disease, or both. National Institute for Health and Clinical Excellence. September 2014. http://www.nice.org.uk/guidance/cg184/chapter/1-recommendations#/#helicobacter-pylori-testing-and-eradication Accessed 30.09.14. RATIONALE: NICE give guidance on when to consider H pylori test and treat in primary care and the treatment regimens based on an extensive systematic review of the efficacy of regimens in countries with similar resistant rates to the UK. First-line H pylori eradication: NICE recommend a twice daily full-dose PPI (Esomeprazole 20mg, Lansoprazole 30mg, Omeprazole 20-40mg, Pantoprazole 40mg, Rabeprazole 20mg) plus amoxicillin (as very little resistance) with either clarithromycin or metronidazole for first line therapy in patients who are not allergic to penicillin. A similar regimen with amoxicillin is recommended second line using amoxicillin with the second agent (clarithromycin or metronidazole that has not previously been used). Second-line in patients previously exposed to metronidazole and clarithromycin they recommend PPI plus tetracycline plus levofloxacin.
NICE recommend that consideration should be given to avoiding clarithromycin or levofloxacin if previously used for other infections.
In penicillin allergic patients NICE recommend a twice daily full-dose PPI with clarithromycin and metronidazole. In allergic patients who have had clarithromycin previously for another infection they recommend PPI plus, bismuthate (De-Nol), plus tetracycline plus metronidazole.
Duration of treatment: although 14-day triple therapy gives almost a 10% higher eradication rate, the absolute benefit of H pylori therapy is modest in NUD and undiagnosed dyspepsia and the longer duration of therapy does not appear cost effective. In patients with PUD increasing the course to 14 days also gives a nearly 10% higher eradication rate, but does not appear cost effective.
MALToma: expert opinion is that for MALT lymphoma, the increased efficacy of a 14-day regimen will reduce the need for chemotherapy and/or gastric resection.

2
Malfertheiner P, Megraud F, O’Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuiper EJ, The European Helicobacter Study Group (EHSG). Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 2007;56:772-781. RATIONALE: MALToma: sixty two percent of patients with low grad gastric MALT lymphoma have complete remission after H pylori eradication within 12 months. Second-line treatment: bismuth-based quadruple therapy is a preferred option.

3
Moayyedi P, Soo S, Deeks JJ, Delaney B, Harris A, Innes M, Oakes R, Wilson S, Roalfe A, Bennett C, Forman D. Eradication of Helicobacter pylori for non-ulcer dyspepsia. The Cochrane library 2006. Issue 2 http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD002096/frame.html Accessed 23.09.14. RATIONALE: Pooled data from 17 RCTS (n = 3566) found there was a 10% relative risk reduction in dyspepsia symptoms in people with non-ulcer dyspepsia randomized to receive H pylori eradication (95% CI 6% to 14%) compared to placebo. The NNT to cure one case of dyspepsia was 14 (95% CI 10 to 25).

4
Delaney BC, Qume M, Moayyedi P, Logan RFA, Ford AC, Elliott C, McNulty C, Wilson S, Hobbs FDR. Helicobacter pylori test and treat versus proton pump inhibitor in initial management of dyspepsia in primary care: multicentre randomised controlled trial (MRC-CUBE trial). BMJ 2008; 336: 651-654. RATIONALE: At 12 months, there were no significant differences in QALYs, costs, or dyspeptic symptoms between the group assigned to initial H pylori test and treat and the group assigned to initial acid suppression (n = 699).

5
Fischbach L and 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; 26: 343-357. RATIONALE: Pooled data found that the efficacy of a PPI + clarithromycin + metronidazole was reduced more by resistance to clarithromycin than by resistance to metronidazole. Metronidazole resistance reduced efficacy by 18% while clarithromycin resistance was estimated to reduce efficacy by 35%. Clarithromycin resistance reduced the efficacy of a PPI + clarithromycin + amoxicillin by 66%.

6
McNulty CAM, Lasseter G, Shaw I, Nichols T, D'Arcy S, Lawson A, Glocker E. Is Helicobacter pylori antibiotic resistance surveillance needed and how can it be delivered? Aliment Pharmacol Ther 2012; 35: 1221–1230. RATIONALE. This study determined the prevalence of H. pylori antibiotic resistance in patients attending endoscopy in England and Wales, and the feasibility of an antibiotic resistance surveillance programme testing. H.pylori were cultured in 6.4% of 2063 patients attending Gloucester and Bangor hospitals. Resistance to amoxicillin, tetracycline and rifampicin/rifabutin was below 3% at all centres. Clarithromycin, metronidazole and quinolone resistance was significantly higher in HRU (68%, 88%, 17%) and Bangor isolates (18%, 43%, 13%) than Gloucester (3%, 22%, 1%). Each previous course of these antibiotics was associated with an increase in the risk of antibiotic resistance to that agent [clarithromycin: RR = 1.5 (P = 0.12); metronidazole RR = 1.6 (P = 0.002); quinolone RR = 1.8 (P = 0.01)].

7
Luther J, Higgins PDR, Schoenfield PS, Moayyedi P, Vakil N, Chey WD. Empiric quadruple vs. triple therapy for primary treatment of Helicobacter pylori infection: systematic review and meta-analysis of efficacy and tolerability. Am J Gastroenterol 2010;105: 65-73. RATIONALE: Pooled data from 9 RCTs (n = 1679) found that eradication rates were comparable between clarithromycin triple therapy (77%) and bismuth-containing quadruple therapy (78%). Most trials of 7-10 days duration.
8
Public Health England recommends that oxytetracycline is not substituted for tetracycline hydrochloride as part of the quadruple therapy regimen. Oxytetracycline is thought to have different mucus penetration properties to tetracycline hydrochloride. In addition, the treatment studies have been done with tetracycline hydrochloride. If third line treatment is required clinicians may also consider changing the PPI to rabeprazole, as it has a different metabolism to the other PPIs which may be metabolised rapidly in some patients, causing treatment failure.

9
Fuccio L, Minardi ME, Zagari RM, Grilli D, Magrini N, Bazzoli F. Meta-analysis: duration of first-line proton-pump inhibitor based triple therapy for Helicobacter pylori eradication.
Annals Internal Medicine 2007; 147: 553-562. RATIONALE: Pooled data found that extending the course of triple therapy from 7 to 14 days increased eradication rates only by about 5% (no statistically significant difference). The authors concluded that this is unlikely to be a clinically useful difference.

The POCAST project is funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London and by the Imperial College Healthcare Charity (Grant Ref No:7006/P36U).