Contents

Search

Helicobacter pylori

First described in 1983 by Marshall & Warren in relation to histologic gastritis. The first successful therapy for H pylori (bismuth-based triple therapy for 2 weeks) was described in 1991. Response to therapy has been shown for peptic ulcer disease & gastric lymphoma. Epidemiology: 1) H. pylori occurs worldwide a) infects 50% of people worldwide b) infects 30-40% of U.S. population 2) reservoir of its infection & its mode of transmission are unknown 3) most infection with H.pylori is acquired during childhood 4) prevalence of gastritis associated with H. pylori increases with age Pathology: 1) Helicobacter pylori is associated with a) major cause of chronic gastritis in US - associated with 70-90% of gastric ulcers - atrophic gastritis b) dyspepsia without ulceration c) duodenal ulcer: 1] primary etiologic factor in peptic ulcer disease in the US 2] associated with 95-99% of duodenal ulcers d) gastric carcinoma e) gastric lymphoma, MALT lymphoma, lymphocytic gastritis 2) host factors a) smoking b) blood type O 3) microbial factors - cytotoxin or vacuolating toxin 4) enhanced gastrin response to stimulation 5) enhanced acid production in response to gastrin 6) impaired somatostatin release from gastrin D cells 7) inflammatory response to infection 8) gastric metaplasia of duodenal bulb 9) spontaneous eradication of the organism is rare Genetics: - genetic variation in the IFNGR1 gene is associated with susceptibility to Helicobacter pylori infection Clinical manifestations: 1) atopic dermatitis 2) asthma 3) peptic ulcer disease (PUD) - only 15% of patients with H. pylori will develop PUD Laboratory: 1) H pylori serology (sensitivity 88-94%, specificity 74-88%) a) do not use serological testing for proof of cure after treatment b) antibody titers remain elevated > 1 year after successful eradication [3] c) only test not affected by proton pump inhibitors or recent gastrointestinal hemorrhage [3] d) H pylori IgG in serum [3] e) positive test not confirmatory for diagnosis f) negative test excludes diagnosis 2) testing based upon urease activity of H. pylori a) carbon-labeled urea breath testing - sensitivity 90-96%, specificity 88-98% - may be best test in children - useful for follow-up testing (proof of cure) [3] - all patients [3] b) rapid urease assay (Clotest) - specimen obtained during endoscopy - sensitivity 88-95%, specificity 95-100% 3) Helicobacter pylori culture & histologic evaluation of endoscopic biopsies - sensitivity 80-98%, specificity 98-100% 4) Helicobacter pylori antigen - H pylori stool antigen test HpSA [6,13] - especially useful for assessment of H pylori eradication after treatment [3] - sensitivity 94%, specificity 92% 5) Helicobacter pylori DNA (not widely available) [3] 6) indications for H pylori testing a) uninvestigated dyspepsia - cost effective for patients with dyspepsia, not related to NSAID use [19] b) peptic ulcer c) MALT lymphoma d) endoscopic resection of gastric cancer e) screening & treatment of asymptomatic individuals may benefit some patients [17] f) testing asymptomatic persons not recommended [44,48] 7) see ARUP consult [26] 8) follow-up testing with urea breath testing or H pylori stool antigen test indicated due to 25% treatment failure no sooner than 4 weeks after completion of therapy [3] * patients should stop proton pump inhibitors 1-2 weeks prior to laboratory testing since proton pump inhibitors suppress growth of the organism Special laboratory: - upper GI endoscopy with biopsy generally unnecessary to document H. pylori infection or eradication in patients < 60 years with low risk for malignancy & no alarm symptoms, such as weight loss or anemia [3] - may document presence of gastric lymphoma, MALT lymphoma Complications: 1) increased incidence of atrophic gastritis in connection with use of proton pump inhibitor 2) increased incidence of gastric adenocarcinoma [21] & lymphoma a) classified as a carcinogen by the WHO (World Health Organization) b) 60-70% of gastric carcinomas causally related to H pylori - risk is small [48] (consider esophageal carcinoma if Barrett's esophagus) c) 90% of gastric lymphomas causally related to H pylori - MALT lymphoma d) no association found between H.pylori infection & gastric cancer in women [4] e) eradication of H pylori diminishes risk of gastric cancer [8,34,47] f) high genetic risk of gastric cancer counteracted by H pylori treatment [50] 3) increased incidence of gastric mucosa-associated lymphoid tissue MALT lymphoma - may regress following eradication of H pylori 4) increased risk of peptic ulcer in combination with NSAIDs [10,11] 5) gastric intestinal metaplasia 6) lymphocytic gastritis (rare) [3] Management: 1) BMTL regimen: 10-14 days (bismuth quadruple therapy) [39] - first line treatment [48]; 14 days of treatment, 10 days inadequate [52] - bismuth subsalicylate 2 tablets QID - bismuth tripotassium dicitrate used in [39] - metronidazole 250 mg QID - tetracycline 500 mg QID; substitution with doxycycline weakens therapy [52] - lansoprazole 15 mg QID - 90% effective, adverse effects in 67% (both highest) [39] - prior 7 days of therapy - longer duration of therapy as determined by repeat upper GI endoscopy for MALT lymphoma - confirm eradication of H pylori at the conclusion of treatment [42,43,48] 2) vonoprazan-amoxicillin regimen: 10 days ( best-integrated efficacy-safety profile) [53] - vonoprazan 20 mg BID + amoxicillin 1000 mg TID +/- clarithromycin 500 mg BID - 10 day dual course (vonoprazan-amoxicillin) reportedly non-inferior to 14 day course of BMTL regimen [49] - vonoprazan 20 mg BID + tetracycline 500 mg TID if penicillin allergy [51] 3) ACL regimen: 14 days 1st line [22] (82% cure rate) [14,22] - amoxicillin 1000 mg BID - clarithromycin 500 mg BID - lansoprazole 30 mg BID or other proton pump inhibitor* BID 4) triple therapy (Helidac kit, Pylera): 10-14 days [3,22] - tetracycline 500 mg QID or amoxicillin 500 mg QID - metronidazole 250 mg TID - bismuth subsalicylate (Pepto-Bismol) 2 tablets QID - add omeprazole 20 mg BID for quadruple therapy (OBMT regimen)* [3,22,24], 80% eradication [24] - add probiotic for probiotic-supplemented triple therapy* 5) AML regimen: 7 days - amoxicillin 1000 mg BID - metronidazole 500 mg BID - lansoprazole 30 mg BID 6) CML regimen: 14 days - clarithromycin 500 mg BID - metronidazole 500 mg BID - lansoprazole 30 mg BID 7) Four-drug therapy: 7,10,or 14 days [12,25,36] (concomittant therapy)* - amoxicillin 1000 mg BID - metronidazole 400 mg BID - clarithromycin 250 mg BID - lanzoprazole 30 mg or ranitidine 300 mg BID 8) nitroimidazole therapy 10-14 days (not validated in North America) - amoxicillin 1000 mg BID - clarithromycin 500 mg BID - nitroimidazole 500 mg BID - lansoprazole 30 mg BID [3] 9) sequential therapy improves eradication rates [28,31]* - lansoprazole 30 mg & amoxicillin 1 g BID for 7 days followed by - lansoprazole 30 mg, clarithromycin 500 mg & metronidazole 500 mg BID for 7 days [28] - proton pump inhibitor plus amoxicillin BID for 5 days followed by - proton pump inhibitor plus clarithromycin plus metronidazole BID for 5 days [31] - for strains resistant to both clarithromycin & metronidazole, substitution of levofloxacin for clarithromycin increases efficacy 10) hybrid therapy for 14 days* - proton pump inhibitor (PPI) & amoxicillin used for 7 days, followed by a PPI, amoxicillin, clarithromycin, & 5-nitroimidazole for another 7 days* 11) treatment failure a) course of different antibiotics [3] - replace clarithromycin with fluoroquinolone [3,37] - 10-14 day course, 14 day course [3] - BMTL regimen recommended for ACL regimen failure [3,48] b) antibiotic resistance / resistant cases [7] - metronidazole resistance (10-50%, 37%) - lansoprazole 30 mg + bismuth potassium citrate 220 mg BID & one of the following: [30] - tetracycline 500 mg + metronidazole 400 mg QID (LBTM) - tetracycline 500 mg QID + furazolidone 100 mg TID (LBTF) - amoxicillin 1 g TID + tetracycline 500 mg QID (LBAT) - amoxicillin 1 g TID + furazolidone 100 mg TID (LBAF) - rifabutin 300 mg PO QD + amoxicillin 1000 mg PO BID + pantoprazole 40 mg PO BID for 10 days - levofloxacin 500 mg PO QD + amoxicillin 1000 mg PO BID + omeprazole 20 mg PO BID [18] - clarithromycin resistance (10-15%) [39] 12) pregnant women: erythromycin 500 mg PO BID 13) treat H pylori before beginning chronic NSAID, corticosteroid, or anticoagulant [10] 14) H pylori eradication does not relieve dyspepsia in the absence of ulcer [14] 15) antibiotic treatment may lead to colonization with antibiotic-resistant organisms [15] 16) eradication may diminish progression of premalignant gastric lesions [20,38] 17) recurrence of bleeding peptic ulcer after eradication of H pylori is rare [27] even with continued use of aspirin [32] 18) vitamin C, vitamin E, selenium, beta-carotene & garlic extract/oil for 7 years may be of benefit [47] 19) treatment of asymptomatic contacts does not improve outcomes [48] * initial treatments of choice [25] * use of 1/2 dose clarithromycin in combination therapy associated with lower risk of adverse effects (29% vs 44%) & similar eradication rate (82% vs 83%) [35] * esomeprazole dosed QD [3]

Related

Campylobacter-like organism (CLO) test (rapid urease assay, Pylori-Tek, Hp-fast) carbon-labeled urea breath testing (BreathTek UBT) extranodal marginal zone B-cell lymphoma; low grade B-cell lymphoma of MALT [mucosa associated lymphoid tissue] type, MALToma Helicobacter pylori (H pylori) stool/tissue antigen assay Helicobacter pylori antibody urease

General

Helicobacter

Properties

KINGDOM: monera DIVISION: SCHIZOMYCETES

Database Correlations

OMIM 600263

References

  1. Clinical Diagnosis & Management by Laboratory Methods, 19th edition, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1996, pg 1160
  2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 319-321
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Journal Watch 20(16):130, 2000 Yamagata et al 160:1962, 2000
  5. Journal Watch 20(17):136-37, 2000
  6. Journal Watch 20(16):131, 2000 Braden B et al Pediatrics 106:115, 2000
  7. Prescriber's Letter 8(4):21 2001
  8. Journal Watch 21(19):151, 2001 Uemura et sl N Engl J Med 345:784, 2001
  9. Prescriber's Letter 8(11):65 2001
  10. Prescriber's Letter 9(3):16 2002
  11. Journal Watch 22(5):35, 2002 Huang J-Q et al, Lancet 359:14, 2002 Chan FKL et al, Lancet 359:9, 2001 Pounder RE, Lancet 359:3, 2001
  12. Journal Watch 22(6):45, 2002 Treiber et al, Arch Intern Med 162:153, 2002 (MALCOR study)
  13. Journal Watch 22(7):55, 2002 Vairi et al, Ann Intern Med 136:280, 2002
  14. Journal Watch 23(21):168, 2003 Veldhuyzen van Zanten S, Fedorak RN, Lambert J, Cohen L, Vanjaka A. Absence of symptomatic benefit of lansoprazole, clarithromycin, and amoxicillin triple therapy in eradication of Helicobacter pylori positive, functional (nonulcer) dyspepsia. Am J Gastroenterol 98:1963, 2003 PMID: 14499772 - Kearney DJ, Liu CF, Crump C, Brousal A. The effect of a Helicobacter pylori treatment strategy on health care expenditures in patients with peptic ulcer disease and dyspepsia. Am J Gastroenterol 98:1952, 2003 PMID: 14499771
  15. McMahon BJ, Hennessy TW, Bensler JM, Bruden DL, Parkinson AJ, Morris JM, Reasonover AL, Hurlburt DA, Bruce MG, Sacco F, Butler JC. The relationship among previous antimicrobial use, antimicrobial resistance, and treatment outcomes for Helicobacter pylori infections. Ann Intern Med 139:463, 2003 PMID: 13679322 - Sjolund M, Wreiber K, Andersson DI, Blaser MJ, Engstrand L. Long-term persistence of resistant Enterococcus species after antibiotics to eradicate Helicobacter pylori. Ann Intern Med 139:483, 2003 PMID: 13679325
  16. Journal Watch 25(7):58, 2005 Megraud F; European Paediatric Task Force on Helicobacter pylori. Comparison of non-invasive tests to detect Helicobacter pylori infection in children and adolescents: results of a multicenter European study. J Pediatr. 2005 Feb;146(2):198-203. PMID: 15689908
  17. Lane JA, Murray LJ, Noble S, Egger M, Harvey IM, Donovan JL, Nair P, Harvey RF. Impact of Helicobacter pylori eradication on dyspepsia, health resource use, and quality of life in the Bristol helicobacter project: randomised controlled trial. BMJ. 2006 Jan 28;332(7535):199-204. Epub 2006 Jan 20. PMID: 16428249 - Delaney BC. Who benefits from Helicobacter pylori eradication? BMJ. 2006 Jan 28;332(7535):187-8. No abstract available. PMID: 16439372
  18. Prescriber's Letter 13(5): 2006 Levofloxacin for persistent Helicobacter pylori infection Detail-Document#: 220512 (subscription needed) http://www.prescribersletter.com
  19. Jarbol DE, Kragstrup J, Stovring H, Havelund T, Schaffalitzky de Muckadell OB. Proton pump inhibitor or testing for Helicobacter pylori as the first step for patients presenting with dyspepsia? A cluster-randomized trial. Am J Gastroenterol. 2006 Jun;101(6):1200-8. PMID: 16771937
  20. You WC, Brown LM, Zhang L, Li JY, Jin ML, Chang YS, Ma JL, Pan KF, Liu WD, Hu Y, Crystal-Mansour S, Pee D, Blot WJ, Fraumeni JF Jr, Xu GW, Gail MH. Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. J Natl Cancer Inst. 2006 Jul 19;98(14):974-83. PMID: 16849680
  21. Kamangar F et al, Opposing risks of gastric cardia and non cardia gastric adenocarcinomas associated with Helicobacter pylori seropositivity. J Natl Cancer Inst 2006, 98:1445 PMID: 17047193
  22. Prescriber's Letter 14(6): 2007 H. Pylori Treatment Regimens Detail-Document#: 230604 (subscription needed) http://www.prescribersletter.com - Prescriber's Letter 14(11): 2007 H. Pylori Treatment Regimens Detail-Document#: 231113 (subscription needed) http://www.prescribersletter.com
  23. Prescriber's Letter 17(12): 2010 COMMENTARY: H. Pylori Treatment: Is Quadruple Therapy Making a Comeback? CHART: H. Pylori Treatment Regimens GUIDELINES: American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection Detail-Document#: 261204 (subscription needed) http://www.prescribersletter.com
  24. Malfertheiner P et al. Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: A randomised, open-label, non-inferiority, phase 3 trial. Lancet 2011 Feb 22 PMID: 21345487
  25. Prescriber's Letter 19(2): 2012 COMMENTARY: H. Pylori Treatment: An Update CHART: H. Pylori Treatment Regimens GUIDELINES: American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection (2007) Detail-Document#: 280222 (subscription needed) http://www.prescribersletter.com
  26. ARUP Consult: Helicobacter pylori The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/helicobacter-pylori - Helicobacter pylori Testing Algorithm https://arupconsult.com/algorithm/helicobacter-pylori-testing-algorithm
  27. Gisbert JP et al. Long-term follow-up of 1,000 patients cured of Helicobacter pylori infection following an episode of peptic ulcer bleeding. Am J Gastroenterol 2012 Aug; 107:1197. PMID: 22613904
  28. Liou J-M et al Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet 2012 Nov 15 PMID: 23158886 - Greenberg ER and Chey WD. Defining the role of sequential therapy for H. pylori infection. Lancet 2012 Nov 15; PMID: 23158881
  29. Chan FKL et al. Effects of Helicobacter pylori infection on long-term risk of peptic ulcer bleeding in low-dose aspirin users. Gastroenterology 2013 Mar; 144:528. PMID: 23333655
  30. Liang X et al. Efficacy of bismuth-based quadruple therapies for clarithromycin-, metronidazole-, and fluoroquinolone- resistant Helicobacter pylori infections in a prospective study. Clin Gastroenterol Hepatol 2013 Jul; 11:802 PMID: 23376004 http://www.cghjournal.org/article/S1542-3565(13)00116-X/abstract
  31. Mueller PS N Engl J Med Journal Watch. September 12, 2013 Massachusetts Medical Society http://www.jwatch.org - Gatta L et al. Global eradication rates for Helicobacter pylori infection: Systematic review and meta-analysis of sequential therapy. BMJ 2013 Aug 7; 347:f4587 PMID: 23926315 http://www.bmj.com/content/347/bmj.f4587
  32. Chey WD, Wong BC; Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007 Aug;102(8):1808-25. PMID: 17608775
  33. McColl KE. Clinical practice. Helicobacter pylori infection. N Engl J Med. 2010 Apr 29;362(17):1597-604 PMID: 20427808
  34. Ford AC et al Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials. BMJ 2014;348:g3174 PMID: 24846275 http://www.bmj.com/content/348/bmj.g3174
  35. Harb AH et al. Systematic review and meta-analysis: Full- vs. half-dose anti-microbials in clarithromycin-based regimens for Helicobacter pylori eradication. Aliment Pharmacol Ther 2015 May 24 PMID: 26011564
  36. Li BZ, P Threapleton DE, Wang JW et al Comparative effectiveness and tolerance of treatments for Helicobacter pylori: systematic review and network meta-analysis. BMJ 2015;351:h4052 PMID: 26290044 http://www.bmj.com/content/351/bmj.h4052 - Braden B The best and worst treatments for Helicobacter pylori BMJ 2015;351:h4146 PMID: 26290321 http://www.bmj.com/content/351/bmj.h4146
  37. Luther J, Chey WD, Saad RJ. A clinician's guide to salvage therapy for persistent Helicobacter pylori infection. Hosp Pract (1995). 2011 Feb;39(1):133-40. Review. PMID: 21441768
  38. Lee YC, Chiang TH, Chou CK et al. Association between Helicobacter pylori eradication and gastric cancer incidence: A systematic review and meta-analysis. Gastroenterology 2016 Jan 30 PMID: 26836587 Free Article
  39. Liou JM, Fang YJ, Chen CC et al Concomitant, bismuth quadruple, and 14-day triple therapy in the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet Oct 18, 2016 PMID: 27769562 http://thelancet.com/journals/lancet/article/PIIS0140-6736(16)31409-X/fulltext - Megraud F, Gisbert JP Towards effective empirical treatment for Helicobacter pylori eradication. Lancet Oct 18, 2016 PMID: 27769561 http://thelancet.com/journals/lancet/article/PIIS0140-6736(16)31657-9/fulltext
  40. Malfertheiner P, Megraud F, O'Morain CA et al Management of Helicobacter pylori infection-the Maastricht V/ Florence Consensus Report. Gut. 2016 Oct 5. pii: gutjnl-2016-312288. PMID: 27707777
  41. Nyssen OP, McNicholl AG, Megraud F et al Sequential versus standard triple first-line therapy for Helicobacter pylori eradication. Cochrane Database Syst Rev. 2016 Jun 28;(6):CD009034. Review. PMID: 27351542
  42. Lopes AI, Vale FF, Oleastro M. Helicobacter pylori infection - recent developments in diagnosis. World J Gastroenterol. 2014 Jul 28;20(28):9299-313. Review. PMID: 25071324 Free PMC Article
  43. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017 Feb;112(2):212-239. PMID: 28071659
  44. Crowe SE Helicobacter pylori Infection. N Engl J Med 2019; 380:1158-1165. March 21. PMID: 30893536 https://www.nejm.org/doi/full/10.1056/NEJMcp1710945
  45. Rothaus C. Helicobacter pylori Infection NEJM Resident 360. March 20, 2019 https://resident360.nejm.org/content_items/helicobacter-pylori-infection
  46. Nam SY, Park BJ, Nam JH, Kook MC. Effect of Helicobacter pylori eradication and high-density lipoprotein on the risk of de novo gastric cancer development. Gastrointest Endosc 2019 Apr 26. PMID: 31034810 https://www.giejournal.org/article/S0016-5107(19)31659-1/pdf - Nam SY, Park BJ, Ryu KH, Nam JH. Effect of Helicobacter pylori eradication on the regression of gastric polyps in National Cancer Screening Program. Korean J Intern Med. 2018 May;33(3):506-511. Epub 2017 Dec 14. PMID: 29232943 Free PMC Article
  47. Li WQ, Zhang JY, Ma JL et al Effects of Helicobacter pylori treatment and vitamin and garlic supplementation on gastric cancer incidence and mortality: follow-up of a randomized intervention trial. BMJ 2019;366:l5016 PMID: 31511230 Free Article https://www.bmj.com/content/366/bmj.l5016
  48. NEJM Knowledge+ Gastroenterology
  49. Yan TL, Wang JH, He XJ, et al. Ten-Day Vonoprazan-Amoxicillin Dual Therapy vs Standard 14-Day Bismuth-Based Quadruple Therapy for First-Line Helicobacter pylori Eradication: A Multicenter Randomized Clinical Trial. Am J Gastroenterol. 2023 Dec 11 PMID: 37975609 https://journals.lww.com/ajg/fulltext/9900/ten_day_vonoprazan_amoxicillin_dual_therapy_vs.935.aspx
  50. Xu HM, Han Y, Liu ZC Helicobacter pylori Treatment and Gastric Cancer Risk Among Individuals With High Genetic Risk for Gastric Cancer. JAMA Netw Open. 2024 May 1;7(5):e2413708. doi: 10.1001/jamanetworkopen.2024.13708. PMID: 38809553 PMCID: PMC11137637 Free PMC article.
  51. Gao W, Liu J, Wang X, et al. Simplified Helicobacter pylori therapy for patients with penicillin allergy: a randomised controlled trial of vonoprazan-tetracycline dual therapy. Gut. 2024 Jun 21:gutjnl-2024-332640. PMID: 38906695 Free article
  52. Chey W et al. ACG clinical guideline: Treatment of Helicobacter pylori infection. Am J Gastroenterol 2024 Sep; 119:1730. Not yet indexed in PubMed https://journals.lww.com/ajg/fulltext/2024/09000/acg_clinical_guideline__treatment_of_helicobacter.13.aspx
  53. Rokkas T, Ekmektzoglou K, Niv Y, et al. Comparative Efficacy and Safety of Potassium-Competitive Acid Blocker-Based Dual, Triple, and Quadruple Regimens for First-Line Helicobacter pylori Infection Treatment: A Systematic Review and Network Meta-Analysis. Am J Gastroenterol. 2024 Sep 19 PMID: 39298553 https://journals.lww.com/ajg/abstract/9900/comparative_efficacy_and_safety_of.1334.aspx