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Helicobacter pylori Infection

By

Nimish Vakil

, MD, University of Wisconsin School of Medicine and Public Health

Reviewed/Revised Mar 2023
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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 result in varying degrees of dyspepsia. Diagnosis is by urea breath test, stool antigen test, and testing of endoscopic biopsy samples. Treatment is typically with a proton pump inhibitor plus two antibiotics and often bismuth subsalicylate.

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 Peptic Ulcer Disease .

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.

Pathophysiology reference

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.

  • 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

  • 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 ).

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.

Drugs Mentioned In This Article

Drug Name Select Trade
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
Heartburn Relief, Prevacid, Prevacid 24HR, Prevacid IV , Prevacid Solutab
Prilosec, Prilosec OTC
First-Pantoprazole, Protonix
Aciphex, Aciphex Sprinkle
Nexium, Nexium 24HR, Nexium 24HR Clear Minis
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
Flagyl, Flagyl ER, Flagyl RTU, LIKMEZ, MetroCream, MetroGel, MetroGel Vaginal, MetroLotion, Noritate, NUVESSA, Nydamax, Rosadan, Rozex, Vandazole, Vitazol
Emtet-500, Panmycin, Sumycin
Amoxil, Dispermox, Moxatag, Moxilin , Sumox, Trimox
Biaxin, Biaxin XL
Mycobutin
Iquix, Levaquin, Levaquin Leva-Pak, Quixin
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NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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