Guideline sources The following summarized guidelines for the evaluation and management of Helicobacter pylori infection are prepared by our editorial team based on guidelines from the Italian Society of Digestive Endoscopy (SIDE/SIGE 2022), the American Gastroenterological Association (AGA 2021; 2020), the World Society of Emergency Surgery (WSES 2020), the American Society for Clinical Pathology (ASCP 2019), the European Society for the Study of Coeliac Disease (ESsCD 2019), the American College of Gastroenterology (ACG/CAG 2017), the Maastricht V/Florence Consensus Report (Maastricht V/Florence 2017), the American College of Gastroenterology (ACG 2017; 2013; 2007), the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN/NASPGHAN 2017), the Canadian Association of Gastroenterologists (CAG 2016), and the American Society for Gastrointestinal Endoscopy (ASGE 2010). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 18 19 Definition https://web.pathway.md/diseases/recBlcLq2Gd1rW3fw 1/11 6/24/23, 12:31 PM Helicobacter pylori infection Pathway H. pylori is a Gram-negative bacterium that causes chronic infection and inflammation of the stomach and duodenum. 16 Epidemiology H. pylori infection is transmitted via the fecal-oral and oral-oral routes; horizontal transmission, and environmental transmission through contaminated water also occurs. 18 Pathophysiology The overall prevalence of H. pylori infection is estimated at 30.7% in the United States. However, the distribution is heterogeneous with a higher prevalence in immigrants from high-risk areas (Latin America, Asia). 17 Disease course H. pylori infection is associated with an increased risk of various gastrointestinal diseases including functional dyspepsia, gastritis, peptic ulcer disease, gastric intestinal metaplasia, and gastric cancer. 18 Prognosis and risk of recurrence Although successful eradication of H. pylori infection prevents the development and progression of H. pylori-associated diseases, the efficacy of treatment regimens has decreased due to increased antibiotic resistance. Globally, the annual recurrence, reinfection, and recrudescence rate of H. pylori is 4.3%, 3.1%, and 2.2%, respectively. 19 Guidelines 1. Screening and diagnosis Epidemiology: As per ACG 2017 guidelines: Recognize that H. pylori is a chronic condition and is usually acquired in childhood. B Recognize that the incidence and prevalence of H. pylori infection are generally higher among people born outside North America. Recognize that the prevalence of the infection within North America is higher in certain racial and ethnic groups, the socially disadvantaged, and people who have immigrated to North America. B Recognize that H. pylori resistance rates to antibiotics are increasing in most parts of the world. B Differential diagnosis: exclude H. pylori gastritis before making a reliable diagnosis of functional dyspepsia. A Indications for testing, dyspepsia: https://web.pathway.md/diseases/recBlcLq2Gd1rW3fw 2/11 6/24/23, 12:31 PM Helicobacter pylori infection Pathway As per SIDE/SIGE 2022 guidelines, test for and eradicate H. pylori infection in < 50 years old patients with uninvestigated dyspepsia without alarm symptoms. B As per ACG 2017 guidelines, consider testing for H. pylori infection (with noninvasive methods) in < 60 years old patients with uninvestigated dyspepsia in the absence of alarm features. B As per CAG/ACG 2017 guidelines, test for (with noninvasive methods) and eradicate H. pylori infection in < 60 years old patients with dyspepsia. A Indications for testing, PUD: As per SIDE/SIGE 2022 guidelines, test for and eradicate H. pylori infection in patients taking NSAIDs or aspirin with a history of peptic ulcer. Initial eradication ideally before starting NSAIDs or aspirin therapy to prevent complicated and uncomplicated peptic ulcers. B As per WSES 2020 guidelines, test for H. pylori infection in all patients with bleeding peptic ulcer. B As per ACG 2017 guidelines, test for H. pylori infection in all patients with active peptic ulcer disease, or a past history of peptic ulcer disease (unless the previous cure of H. pylori infection has been documented). A Test for H. pylori infection in aspirin and NSAID users with a history of peptic ulcer. B As per ASGE 2010 guidelines, test for H. pylori infection in all patients with peptic ulcer disease because it is a common etiology. B Indications for testing (NSAID use): Test for and eradicate H. pylori infection in patients initiating chronic treatment with an NSAID. B Consider testing for and eradicating H. pylori infection in patients taking long-term low-dose aspirin, to reduce the risk of ulcer bleeding. C Indications for testing (lymphocytic gastritis): insufficient evidence to recommend routine testing and treatment for H. pylori infection in patients with lymphocytic gastritis. I Indications for testing, GERD: As per SIDE/SIGE 2022 guidelines, eradicate H. pylori infection in patients with GERD on PPI therapy. B As per ACG 2017 guidelines, do not test for H. pylori infection in patients with typical symptoms of GERD without a history of peptic ulcer disease. Treat if tested and found to be positive. D As per ACG 2013 guidelines, do not test for H. pylori infection in patients with GERD. Do not offer eradication therapy routinely as part of antireflux therapy. D Indications for testing, neoplasia: As per AGA 2020 guidelines, test for and eradicate H. pylori infection in patients with gastric intestinal metaplasia. B As per ACG 2017 guidelines, test for H. pylori infection in all patients with low-grade gastric MALT lymphoma, or a history of endoscopic resection of early gastric cancer. B Show 2 more https://web.pathway.md/diseases/recBlcLq2Gd1rW3fw 3/11 6/24/23, 12:31 PM Helicobacter pylori infection Pathway Indications for testing (celiac disease): recognize that H. pylori infection is frequently associated with Marsh 1 intestinal histology and its eradication may lead to normalization of duodenal intraepithelial lymphocyte count. Consider testing for H. pylori infection (with serology or concomitant gastric biopsies) in patients with celiac disease and suspected concomitant H. pylori infection. A Indications for testing (hyperemesis gravidarum): insufficient evidence to recommend routine testing and treatment for H. pylori infection in patients with hyperemesis gravidarum. I Indications for testing, hematological conditions: As per SIDE/SIGE 2022 guidelines, test for and eradicate H. pylori infection in patients with iron, vitamin B12 deficiency anemia, or idiopathic thrombocytopenia. B As per AGA 2020 guidelines, consider testing (with noninvasive methods) for and eradicating H. pylori infection in patients with iron deficiency anemia without other identifiable etiology after upper and lower gastrointestinal endoscopy. C As per ACG 2017 guidelines, test for and eradicate H. pylori infection in patients with unexplained iron deficiency anemia despite an appropriate evaluation, B and in adult patients with immune thrombocytopenia. B Test for and eradicate H. pylori in patients with unexplained iron deficiency anemia, idiopathic thrombocytopenic purpura, and vitamin B12 deficiency. B 2. Diagnostic investigations Choice of diagnostic test: As per SIGE 2022 guidelines, obtain urea breath test or monoclonal ELISA stool antigen test for noninvasive diagnosis of H. pylori infection, both in pre- and post-therapy settings. A Show 2 more As per ASCP 2019 guidelines: Obtain fecal antigen test or urea breath test for the diagnosis of H. pylori infection. B Do not obtain H. pylori serology for the diagnosis of H. pylori infection. D Obtain urea breath test as the first-line noninvasive test in the context of a "test-and-treat strategy". Consider obtaining stool antigen testing as the next option. B Show 3 more As per ACG 2007 guidelines, decide on the choice of the test based on whether the patient requires evaluation with upper endoscopy and an understanding of the strengths, weaknesses, and costs of the individual tests. Show 5 more Culture and sensitivity: As per SIGE 2022 guidelines, consider obtaining culture testing only after multiple treatment failures to choose the most appropriate therapy. C https://web.pathway.md/diseases/recBlcLq2Gd1rW3fw 4/11 6/24/23, 12:31 PM Helicobacter pylori infection Pathway As per AGA 2021 guidelines, consider obtaining H. pylori susceptibility testing to guide the selection of subsequent regimens after two failed therapies with confirmed patient adherence. C Obtain clarithromycin susceptibility testing (either by a standard antibiogram after culture or by a molecular test directly on the gastric biopsy specimen) when a standard clarithromycin-based regimen is considered as the first-line therapy, except in populations or regions with well- documented low clarithromycin resistance (< 15%). B Obtain culture and standard antimicrobial susceptibility testing after a first failure if endoscopy is performed to tailor the treatment, except if a bismuth-based quadruple therapy is considered. B 3. Diagnostic procedures Biopsy: As per SIGE 2022 guidelines, perform histological examination for the diagnosis of H. pylori infection, both in pre- and post-eradication settings, if there is an indication to perform upper gastrointestinal endoscopy with gastric biopsies. Obtain immunohistochemical analysis only in rare cases, such as when chronic/atrophic gastritis is present. B Take two biopsies from the antrum (greater and lesser curvature 3 cm proximal to the pyloric region) and two biopsies from the middle of the body as a minimum standard for the assessment of H. pylori gastritis. Consider taking an additional biopsy from the incisura for the detection of precancerous lesions. B Show 2 more 4. Medical management General principles: As per ACG 2017 guidelines: Recognize that the main determinants of successful H. pylori eradication are the choice of regimen, the patient's adherence to a multi-drug regimen with frequent side effects, and the sensitivity of the H. pylori strain to the combination of antibiotics administered. B Elicit a history of any previous antibiotic exposure and take this information into consideration when choosing a treatment regimen for H. pylori. B Consider employing a test-and-treat strategy for uninvestigated dyspepsia taking into account the regional H. pylori prevalence and cost-benefit considerations. Do not use this strategy in patients with alarm symptoms or older patients. B Show 4 more As per CAG 2016 guidelines, take into account the local antibiotic resistance patterns when deciding on first-line antibiotic therapy in patients with H. pylori infection. B First-line regimens: https://web.pathway.md/diseases/recBlcLq2Gd1rW3fw 5/11 6/24/23, 12:31 PM Helicobacter pylori infection Pathway As per SIGE 2022 guidelines, administer bismuth-based quadruple therapy, concomitant therapy, or sequential therapy as first-line therapy in patients with H. pylori infection. Consider administering a 14-day standard triple therapy only in areas with proven low clarithromycin resistance (< 15%). B As per ACG 2017 guidelines, administer clarithromycin triple therapy (PPI, clarithromycin, and amoxicillin/metronidazole) for 14 days as first-line therapy in patients with no previous history of macrolide exposure for any reason in regions with a low (< 15%) clarithromycin resistance. B Show 3 more Administer a clarithromycin-based triple regimen for 14 days B as first-line empirical therapy in areas with low clarithromycin resistance. Administer bismuth-containing quadruple therapy as an alternative. A Show 4 more As per CAG 2016 guidelines, administer any of the following regimens for 14 days as first-line therapy in patients with H. pylori infection: Situation Guidance PPI, amoxicillin, and clarithromycin B Clarithromycin triple therapy PPI, bismuth, metronidazole, and tetracycline B Traditional bismuth quadruple therapy PPI, amoxicillin, metronidazole, and clarithromycin B Non-bismuth quadruple therapy Show 2 more Management of treatment failure, evaluation: As per SIDE/SIGE 2022 guidelines, obtain upper gastrointestinal endoscopy followed by culture and antimicrobial susceptibility testing to tailor treatment in case of third-line therapy failure. B As per AGA 2021 guidelines, recognize that the usual cause of refractory H. pylori infection (persistent infection after attempting eradication therapy) is antibiotic resistance. Conduct a thorough review of prior antibiotic exposures. B Show 3 more Obtain culture and standard antimicrobial susceptibility testing after a first failure if endoscopy is performed to tailor the treatment, except if a bismuth-based quadruple therapy is considered. B Obtain culture with susceptibility testing or molecular determination of genotype resistance to guide treatment after failure of second-line therapy. B Management of treatment failure (decision to treat): ensure shared decision-making regarding ongoing attempts to eradicate H. pylori in some cases. Weight the potential benefits of H. pylori eradication carefully against the likelihood of adverse effects and inconvenience of repeated exposure to antibiotics and high-dose acid suppression, particularly in vulnerable populations such as the elderly. B https://web.pathway.md/diseases/recBlcLq2Gd1rW3fw 6/11 6/24/23, 12:31 PM Helicobacter pylori infection Pathway Management of treatment failure, choice of regimen: As per SIDE/SIGE 2022 guidelines, administer a levofloxacin-containing regimen as second-line therapy when first-line therapy with single-capsule bismuth quadruple regimen failed, particularly in patients previously exposed to clarithromycin or in a geographical area of known high dual resistance. Asminisrer single-capsule bismuth quadruple therapy as second-line therapy if a clarithromycin-containing regimen was used as the first-line therapy. B Show 2 more As per AGA 2021 guidelines, avoid using clarithromycin- or levofloxacin-based regimens if there is a history of any treatment with macrolides or fluoroquinolones, respectively, given the high likelihood of resistance. D Show 6 more As per ACG 2017 guidelines, avoid using antibiotics previously used by the patient in cases of persistent H. pylori infection. D Show 6 more Administer a bismuth-containing quadruple therapy or a fluoroquinolone-containing triple or quadruple therapy as second-line therapy after failure of clarithromycin triple therapy (PPI, amoxicillin, and clarithromycin). B Show 5 more As per CAG 2016 guidelines, administer bismuth quadruple therapy (consisting of a PPI, bismuth, metronidazole, and tetracycline for 14 days) as an option for subsequent therapy in patients failed to respond to clarithromycin-containing H. pylori eradication therapy. B Show 5 more Management of treatment failure (adjunctive therapies): do not offer adjunctive therapies, including probiotics, for the treatment of refractory H. pylori infection. D 5. Nonpharmacologic interventions Probiotics: As per SIGE 2022 guidelines, consider offering probiotics in addition to eradication therapy to reduce the rate of side effects associated with the eradication therapy. C As per CAG 2016 guidelines, do not offer probiotics in addition to eradication therapy for the purpose of increasing eradication rates or reducing adverse events in patients with H. pylori infection. D 6. Specific circumstances Patients with penicillin allergy: As per AGA 2021 guidelines, consider obtaining penicillin allergy testing in patients labeled as having this allergy, in the absence of a history of anaphylaxis, in order to delist penicillin as an allergy and potentially enable its use. C https://web.pathway.md/diseases/recBlcLq2Gd1rW3fw 7/11 6/24/23, 12:31 PM Helicobacter pylori infection Pathway As per ACG 2017 guidelines, recognize that most patients with a history of penicillin allergy do not have true penicillin hypersensitivity. Consider obtaining penicillin allergy testing after failing the first-line therapy, since the vast majority can ultimately be safely given amoxicillin-containing salvage regimens. B Consider administering clarithromycin triple therapy (PPI, metronidazole, and clarithromycin) as first-line therapy in patients with penicillin allergy in areas of low clarithromycin resistance. Prefer bismuth quadruple therapy in areas of high clarithromycin resistance. C Consider administering a fluoroquinolone-containing regimen as an empirical second-line rescue option in patients with penicillin allergy. C Pediatric patients (diagnosis): diagnose H. pylori infection based on either positive culture or H. pylori gastritis on histopathology with at least 1 other positive biopsy-based test. A Pediatric patients (testing): determine the underlying cause of the symptoms and not solely the presence of H. pylori infection as the primary goal of clinical investigation of gastrointestinal symptoms. Show 9 more Pediatric patients (management): consider offering treatment after careful discussion with the patient/parents if H. pylori infection is an incidental finding at endoscopy. C Pediatric patients (counseling): explain to the family of pediatric patients with H. pylori infection the importance of adherence to the anti-H. pylori therapy to enhance successful eradication. B Pediatric patients (follow-up): Evaluate the effectiveness of first-line therapy in national/regional centers. B Assess the outcome of anti-H. pylori therapy at least 4 weeks after completion of therapy B with any of the following tests: 13C-urea breath test 2-step monoclonal stool H. pylori antigen test. A Pediatric patients (treatment failure): individualize the rescue therapy by taking into account antibiotic susceptibility data, the age of the patient, and available antimicrobial options when H. pylori treatment fails. B 7. Patient education General counseling: recognize that eradication regimens for H. pylori are complex and might not be fully comprehended by patients. B Show 2 more 8. Follow-up and surveillance Post-eradication testing: https://web.pathway.md/diseases/recBlcLq2Gd1rW3fw 8/11 6/24/23, 12:31 PM Helicobacter pylori infection Pathway As per SIGE 2022 guidelines, obtain urea breath test or monoclonal ELISA stool antigen test in the post-therapy setting. A Show 2 more As per ACG 2017 guidelines, obtain urea breath test, fecal antigen test, or biopsy-based testing B to prove eradication in all patients at least 4 weeks after the completion of antibiotic therapy and after interruption of PPI for 2 weeks. B Obtain urea breath test, or monoclonal stool antigen test as an alternative, for confirmation of H. pylori eradication at least 4 weeks after completion of therapy. A Do not obtain a rapid urease test for the assessment of H. pylori eradication after treatment. D 9. Quality improvement Local susceptibility assessment: As per AGA 2021 guidelines, compile local data on H. pylori eradication success rates for each regimen, along with patient demographic and clinical factors (including prior non-H. pylori antibiotic exposure). Make aggregated data publicly available to guide the local selection of H. pylori eradication therapy. B As per ACG 2017 guidelines, attempt to document local, regional, and national patterns of resistance in order to guide the appropriate selection of H. pylori therapy. B Recognize that susceptibility-based results simultaneously provide results both for the individual patient and the population. B Likelihood Ratios Pertinent positives The following findings increase the probability of Helicobacter pylori infection in adults. -1 Finding LR+ Value Positive urea breath test 11.6 Positive rapid urease testing 9.6 Presence of H. pylori 7 Positive stool H. pylori antigen 2.9 does not differentiate between current and prior infection Show 1 more Pertinent negatives The following findings decrease the probability of Helicobacter pylori infection in adults. -1 Finding LR- Value Negative urea breath test 0.1 Negative serum anti-H. pylori antibodies* 0.2 https://web.pathway.md/diseases/recBlcLq2Gd1rW3fw 9/11 6/24/23, 12:31 PM Helicobacter pylori infection Pathway Negative stool H. pylori antigen 0.2 Absence of H. pylori 0.3 does not differentiate between current and prior infection Show 1 more References 1. Paul Moayyedi, Brian E Lacy, Christopher N Andrews et al. ACG and CAG Clinical Guideline: Management of Dyspepsia. Am J Gastroenterol. 2017 Jul;112 7 988 1013. Open 2. 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