(See also Overview of Acid Secretion Overview of Acid Secretion Acid is secreted by parietal cells in the proximal two thirds (body) of the stomach. Gastric acid aids digestion by creating the optimal pH for pepsin and gastric lipase and by stimulating pancreatic... read more and Overview of Gastritis Overview of Gastritis Gastritis is inflammation of the gastric mucosa caused by any of several conditions, including infection (Helicobacter pylori), drugs (nonsteroidal anti-inflammatory drugs, alcohol),... read more 
.)
H. pylori is a spiral-shaped, gram-negative organism that has adapted to thrive in acid. In low- and middle-income countries, it commonly causes chronic infections and is usually acquired during childhood. In the United States, infection is less common among children but increases with age: by age 60, about 50% of people are infected. Infection is most common among Black, Hispanic, and Asian people.
The organism has been cultured from stool, saliva, and dental plaque, which suggests oral-oral or fecal-oral transmission. Infections tend to cluster in families and in residents of custodial institutions. Nurses and gastroenterologists seem to be at high risk because bacteria can be transmitted by improperly disinfected endoscopes.
Pathophysiology of H. pylori Infection
Effects of H. pylori infection vary depending on the location within the stomach.
Antral-predominant infection results in increased gastrin production, probably via local impairment of somatostatin release. Resultant hypersecretion of acid predisposes to prepyloric and duodenal ulcer Peptic Ulcer Disease A peptic ulcer is an erosion in a segment of the gastrointestinal mucosa, typically in the stomach (gastric ulcer) or the first few centimeters of the duodenum (duodenal ulcer), that penetrates... read more 
.
Body-predominant infection leads to gastric atrophy and decreased acid production, possibly via increased local production of interleukin-1 beta. Patients with body-predominant infection are predisposed to gastric ulcer Peptic Ulcer Disease A peptic ulcer is an erosion in a segment of the gastrointestinal mucosa, typically in the stomach (gastric ulcer) or the first few centimeters of the duodenum (duodenal ulcer), that penetrates... read more and gastric adenocarcinoma Stomach Cancer Etiology of stomach cancer is multifactorial, but Helicobacter pylori plays a significant role. Symptoms include early satiety, obstruction, and bleeding but tend to occur late in the... read more 
.
Some patients have mixed infection of both antrum and body with varying clinical effects. Many patients with H. pylori infection have no noticeable clinical effects.
Ammonia produced by H. pylori enables the organism to survive in the acidic environment of the stomach and may erode the mucus barrier. Cytotoxins and mucolytic enzymes (eg, bacterial protease, lipase) produced by H. pylori may play a role in mucosal damage and subsequent ulcerogenesis.
Infected people are 3 to 6 times more likely to develop stomach cancer. H. pylori is a group 1 carcinogen (1 Pathophysiology reference Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more ). H. pylori infection is associated with intestinal-type adenocarcinoma of the gastric body and antrum but not cancer of the gastric cardia. Other associated cancers include gastric lymphoma and mucosa-associated lymphoid tissue (MALT) lymphoma Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma Gastritis is inflammation of the gastric mucosa caused by any of several conditions, including Helicobacter pylori infection, drugs (nonsteroidal anti-inflammatory drugs [NSAIDs], alcohol),... read more , a monoclonally restricted B-cell tumor.
Pathophysiology reference
1. American Cancer Society: Known and probable human carcinogens. 2022. Accessed 1/20/23.
Diagnosis of H. pylori Infection
Urea breath testing and stool antigen testing
Screening of asymptomatic patients is not warranted. Tests are done during evaluation for peptic ulcer and gastritis. Posttreatment testing is typically done to confirm eradication of the organism.
Noninvasive tests
Laboratory and office-based serologic assays for antibodies to H. pylori have a sensitivity and specificity of > 85% and previously were considered the noninvasive tests of choice for initial documentation of H. pylori infection. However, as the prevalence of infection has declined, the percentage of false-positive results with serologic assays has increased significantly, making these tests too unreliable in most countries and regions. As a result, urea breath testing and stool antigen testing are preferred for initial diagnosis. Qualitative assays remain positive for up to 3 years after successful treatment and because quantitative antibody levels do not decline significantly for 6 to 12 months after treatment, serologic assays are not usually used to assess cure.
Urea breath tests use an oral dose of 13C- or 14C-labeled urea. In an infected patient, the organism metabolizes the urea and liberates labeled CO2, which is exhaled and can be quantified in breath samples taken 20 to 30 minutes after ingestion of the urea. Sensitivity and specificity are > 95%. Urea breath tests are well suited for confirming eradication of the organism after therapy. False-negative results are possible with recent antibiotic use or concomitant proton pump inhibitor therapy; therefore, follow-up testing should be delayed ≥ 4 weeks after antibiotic therapy and 1 week after proton pump inhibitor therapy. H2 blockers do not affect the test.
Stool antigen assays have a sensitivity and specificity similar to that of urea breath tests, particularly for initial diagnosis; an office-based stool test is not yet available. Molecular tests for antimicrobial resistance in H. pylori have been developed and are available in Europe.
Invasive tests
Endoscopy is used to obtain mucosal biopsy samples for a rapid urease test (RUT) or histologic staining. Bacterial culture is of limited use because of the fastidious nature of the organism. Endoscopy is not recommended solely for diagnosis of H. pylori; noninvasive tests are preferred unless endoscopy is indicated for other reasons.
The RUT, in which presence of bacterial urease in the biopsy sample causes a color change on a special medium, is the diagnostic method of choice on tissue samples. Histologic staining of biopsy samples should be done for patients with negative RUT results but suspicious clinical findings, recent antibiotic use, or treatment with proton pump inhibitors. RUT and histologic staining each have a sensitivity and specificity of > 90%. Immunohistochemistry is routinely used in some hospital systems and adds to the value of histology because it can be used to detect a very small number of organisms.
Treatment of H. pylori Infection
Antibiotics (various regimens) plus a proton pump inhibitor
For confirmation of cure, urea breath test, stool antigen assay, or upper endoscopy
(See also the American College of Gastroenterology’s [ACG] 2017 guidelines Treatment of Helicobacter pylori Infection and the European 2022 guidelines Management of Helicobacter pylori infection: The Maastricht VI/Florence consensus report.)
Patients with complications (eg, ulcer, cancer) should have the organism eradicated. Eradication of H. pylori can even cure some cases of MALT lymphoma (but not other infection-related cancers).
Treatment of asymptomatic infection has been controversial, but the recognition of the role of H. pylori in cancer has led to a recommendation for treatment.
Vaccines, both preventive and therapeutic (ie, as an adjunct to treatment of infected patients), are under development.
H. pylori eradication requires multidrug therapy, typically antibiotics plus acid suppressants (1 Treatment references Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more ). Proton pump inhibitors suppress H. pylori, and the increased gastric pH accompanying their use can enhance tissue concentration and efficacy of antimicrobials, creating a hostile environment for H. pylori.
Quadruple therapy is the best initial therapy in areas where the clarithromycin resistance rate is > 15% and is recommended in both the European guidelines (2 Treatment references Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more ) and in the ACG guidelines (3 Treatment references Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more ). In quadruple therapy, the following oral medications are given for 14 days (4 Treatment references Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more ):
A proton pump inhibitor (lansoprazole 30 mg 2 times a day, omeprazole 20 mg 2 times a day, pantoprazole 40 mg 2 times a day, rabeprazole 20 mg 2 times a day, or esomeprazole 40 mg once a day)
Bismuth subsalicylate 524 mg 4 times a day
Metronidazole 250 mg 4 times a day
Tetracycline 500 mg 4 times a day
In regions where H. pylori clarithromycin resistance is known to be < 15% and in patients with no previous history of macrolide exposure, triple therapy with the following oral medications for 14 days remains an initial treatment option (2 Treatment references Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more , 3 Treatment references Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more ):
A proton pump inhibitor (lansoprazole 30 mg 2 times a day, omeprazole 20 mg 2 times a day, pantoprazole 40 mg 2 times a day, rabeprazole 20 mg 2 times a day, or esomeprazole 40 mg once a day)
Amoxicillin 1 g 2 times a day or metronidazole 250 mg 4 times a day
Clarithromycin 500 mg 2 times a day
If quadruple therapy fails, the European guidelines suggest dual therapy with a high-dose PPI and amoxicillin or triple therapy with a PPI, amoxicillin, and a fluoroquinolone (2 Treatment references Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more ). There is a high prevalence of fluoroquinolone resistance in the United States, so this strategy may not be applicable there. Triple therapy with low-dose rifabutin, amoxicillin, and a PPI is an alternative (5 Treatment references Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more ). For multidrug-resistant strains of H. pylori, triple therapy with a PPI, rifabutin, and amoxicillin seems to be effective (6 Treatment references Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more ).
The ACG guidelines recommend that triple therapy with clarithromycin not be used if quadruple therapy fails (3 Treatment references Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more ).
The European guidelines suggest double or triple therapy with a potassium-competitive acid inhibitor may be superior or noninferior to standard triple therapy (2 Treatment references Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more , 7 Treatment references Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more ).
Infected patients with duodenal or gastric ulcer require continuation of the acid suppression for at least 4 weeks. Eradication may be confirmed by a urea breath test, stool antigen test, or upper endoscopy done ≥ 4 weeks after completion of therapy. Confirmation of eradication is reasonable in all treated patients but is mandatory in patients who have serious manifestations of H. pylori infection (eg, bleeding ulcer). Recurrent bleeding ulcer is likely if the infection is not eradicated.
If either quadruple or triple therapy fails to eradicate H. pylori, treatment is repeated. If two courses are unsuccessful, some authorities recommend endoscopy to obtain cultures for sensitivity testing. If bismuth quadruple therapy fails, clinicians should engage in a shared decision-making discussion with patients to determine whether they should receive levofloxacin triple therapy (with amoxicillin), rifabutin triple therapy, or an alternate bismuth-containing therapy (8 Treatment references Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more ).
Treatment references
1. Yang JC, Lin CJ, Wang HL, et al: High-dose dual therapy is superior to standard first-line or rescue therapy for Helicobacter pylori infection. Clin Gastroenterol Hepatol 13(5):895–905.e5, 2015. doi: 10.1016/j.cgh.2014.10.036
2. Malfertheiner P, Megraud F, Rokkas T, et al: Management of Helicobacter pylori infection: The Maastricht VI/Florence consensus report. Gut gutjnl-2022-327745, 2022. doi: 10.1136/gutjnl-2022-327745
3. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: Treatment of Helicobacter pylori infection. Am J Gastroenterol 112(2):212–239, 2017. doi: 10.1038/ajg.2016.563. Clarification and additional information. Am J Gastroenterol 113(7):1102, 2018. doi: 10.1038/s41395-018-0132-6
4. Fallone CA, Chiba N, van Zanten SV, et al: The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology 151(1):51–69, 2016. doi: 10.1053/j.gastro.2016.04.006
5. Graham DY, Canaan Y, Maher J, et al: Rifabutin-based triple therapy (RHB-105) for Helicobacter pylori eradication: A double-blind, randomized, controlled trial. Ann Intern Med 172(12):795–802, 2020. doi: 10.7326/M19-3734
6. Fiorini G, Zullo A, Vakil N, et al: Rifabutin triple therapy is effective in patients with multidrug-resistant strains of Helicobacter pylori. J Clin Gastroenterol 52(2):137–140, 2018. doi: 10.1097/MCG.0000000000000540
7. Chey WD, Mégraud F, Laine L, et al: Vonoprazan triple and dual therapy for Helicobacter pylori infection in the United States and Europe: Randomized clinical trial. Gastroenterology 163(3):608–619, 2022. doi: 10.1053/j.gastro.2022.05.055
8. Shah SC, Iyer PG, Moss SF: AGA clinical practice update on the management of refractory Helicobacter pylori infection: Expert review. Gastroenterology 160(5):1831–1841, 2021. doi: 10.1053/j.gastro.2020.11.059
Key Points
H. pylori is a gram-negative organism that is highly adapted to an acid environment and often infects the stomach; incidence of infection increases with age—by age 60, about 50% of people are infected.
Infection predisposes to gastric, prepyloric, and duodenal ulcers and increases risk of gastric adenocarcinoma and lymphoma.
Make initial diagnosis with a urea breath test or stool antigen assay; if endoscopy is being done for other reasons, analyze biopsy samples using a rapid urease test or histologic staining.
Give treatment to eradicate the organism in patients with complications (eg, ulcer, cancer); a typical regimen includes quadruple therapy in areas that have resistance rates to clarithromycin of > 15% or a proton pump inhibitor plus two antibiotics (eg, clarithromycin plus either amoxicillin or metronidazole).
Confirm cure using a urea breath test, stool antigen test, or upper endoscopy.
More Information
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
American College of Gastroenterology: Guidelines for the treatment of Helicobacter pylori infection (2017)
Maastricht VI/Florence consensus report: Management of Helicobacter pylori infection (2022)
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
urea |
Aluvea , BP-50% Urea , BP-K50, Carmol, CEM-Urea, Cerovel, DermacinRx Urea, Epimide-50, Gord Urea, Gordons Urea, Hydro 35 , Hydro 40, Kerafoam, Kerafoam 42, Keralac, Keralac Nailstik, Keratol, Keratol Plus, Kerol, Kerol AD, Kerol ZX, Latrix, Mectalyte, Nutraplus, RE Urea 40, RE Urea 50 , Rea Lo, Remeven, RE-U40, RYNODERM , U40, U-Kera, Ultra Mide 25, Ultralytic-2, Umecta, Umecta Nail Film, URALISS, Uramaxin , Uramaxin GT, Urea, Ureacin-10, Ureacin-20, Urealac , Ureaphil, Uredeb, URE-K , Uremez-40, Ure-Na, Uresol, Utopic, Vanamide, Xurea, X-VIATE |
lansoprazole |
Heartburn Relief, Prevacid, Prevacid IV , Prevacid Solutab |
pantoprazole |
Protonix |
esomeprazole |
Nexium, Nexium 24HR, Nexium 24HR Clear Minis |
bismuth subsalicylate |
Bismatrol , Geri-Pectate, Kaopectate, Kaopectolin , Kao-Tin , K-Pek, Maalox Total Stomach Relief, Peptic Relief , Pepto-Bismol, Pepto-Bismol Maximum Strength, Pepto-Bismol To-Go, Pink Bismuth, Stomach Relief |
metronidazole |
Flagyl, Flagyl ER, Flagyl RTU, MetroCream, MetroGel, MetroGel Vaginal, MetroLotion, Noritate, NUVESSA, Nydamax, Rosadan, Rozex, Vandazole, Vitazol |
tetracycline |
Emtet-500, Panmycin, Sumycin |
amoxicillin |
Amoxil, Dispermox, Moxatag, Moxilin , Sumox, Trimox |
clarithromycin |
Biaxin, Biaxin XL |
rifabutin |
Mycobutin |
levofloxacin |
Iquix, Levaquin, Levaquin Leva-Pak, Quixin |
