Helicobacter Pylori Infection

In 1983, Warren (a biologist) and Marshall (a clinician) described Helicobacter pylori (HP). At first, they named the bacterium Campylobacter pyloridis. Later, it was named Campylobacter pylori. Since then, a large number of reports have been produced on H pylori and its pathogenetic potential.

In fact, although peptic ulcer disease is the most studied disease related to H pylori infection, this bacterium is seemingly involved in the pathogenesis of several extragastric diseases, such as mucosa-associated lymphoid tissue lymphomas (MALTomas), coronaritis (inflammation of coronary arteries), gastroesophageal reflux disease (GERD), iron deficiency anemia, skin disease, and rheumatologic conditions. However, at present, many of these associations remain largely uncertain, and the debate to confirm or refute causality related to these associations is still open.

The association of chronic H pylori infection with alterations in the gastric mucosal cell proliferation is recognized worldwide. In addition, H pylori can produce and release several bioactive factors that may directly affect the stomach's parietal cells, which produce hydrochloric acid, and enterochromaffinlike (ECL) cells (ie, G cells and D cells), which produce gastrin and somatostatin, respectively. Evidence suggests that H pylori inhibits D cells and stimulates G cells. H pylori has some control mechanisms that are able to switch on or off the transcription of different genes when needed. Two histology images are presented below.

Helicobacter Pylori Infection. This image shows an antral gland of the stomach with a large Giemsa-stained colony of Helicobacter pylori in the lumen (arrow) at 250X power. Courtesy of Pantaleo Bufo, University of Foggia, Italy.

Helicobacter Pylori Infection. A lamina propria of the stomach is shown with two mast cells overlapping each other. Note the upper part reveals the degranulating process with the release of granules of inflammation mediators (Giemsa staining, 250X). Courtesy of Pantaleo Bufo, University of Foggia, Italy.

A strong association has been reported between H pylori infection and gastric lymphoma and adenocarcinoma of the body and antrum of the stomach. Some cofactors may play a key role in determining such diseases. Whether H pylori eradication can decrease the risk of cancer is unknown.

H pylori infection occurs more frequently in developing countries than in industrialized countries. H pylori strains differ in their potential to cause diseases. Although anyone can develop a microscopic gastritis, only a minority of infected persons develop ulcers or other diseases. H pylori gastritis is considered an infectious condition, even in the setting of asymptomatic patients and regardless of whether a peptic ulcer or gastric cancer is present.[1]

Some Helicobacter -like organisms (HLOs) have been detected by specific polymerase chain reaction tests. The first of these HLOs was described in ferrets and is called Helicobacter mustelae. Helicobacter hepaticus has been described in Syrian hamsters. These HLOs are useful for researching H pylori infection modalities.

The most common route of H pylori infection is either oral-to-oral (stomach contents are transmitted from mouth to mouth) or fecal-to-oral (from stool to mouth) contact.[2] Parents and siblings seem to play a primary role in transmission.

In a susceptible host, H pylori results in chronic active gastritis that may lead, in turn, to duodenal and gastric ulcer disease, gastric cancer, and MALTomas. H pylori infection causes chronic active gastritis, which is characterized by a striking infiltration of the gastric epithelium and the underlying lamina propria by neutrophils, T and B lymphocytes, macrophages, and mast cells. Mast cells, usually responsible for the immune response balance, may be important effector cells in the pathogenesis of gastritis. However, H pylori does not seem to invade the gastric mucosa, although evidence suggests that the mucus layer provides a niche wherein the bacterium is protected from gastric secretions.

The release of host cytokines after direct contact of H pylori with the epithelial cells of the gastric lining could recall the inflammatory cells in the infected area. One study demonstrated that the gastric epithelium, when infiltrated by neutrophils and macrophages in the lamina propria, highly expresses two neutrophil chemotactic factors: gro-alpha and interleukin-8. In addition, the interferon-gamma inducible protein–10 (IP-10) and the monokine induced by interferon-gamma (MIG), 2 selective chemotactic factors for T lymphocytes, are expressed by the endothelium and mononuclear cells of the gastric mucosa in patients with H pylori -related gastritis. According to the same study, gro-alpha and interleukin-8 may have a central role in neutrophils trafficking from the vessels to the mucosal epithelium, while IP-10 and MIG determine T lymphocyte recruitment into the mucosa.

Another hypothesis states that H pylori may recall immune cells from afar because of its own molecules, such as urea or lipopolysaccharide (LPS). Outer-membrane permeability is a function mediated by LPS. Despite the presence of bacterial LPS in biologically active quantities in the gastric mucosa, the mechanisms by which it may recall the immune cells are still unknown. According to one hypothesis, H pylori may induce the production of autoantibodies against the host's gastric lining.

The LPS of H pylori shows certain blood group antigens, such as Leb, Lex, Ley, and H-type I. Such antigens are thought to represent important virulence factors involved in the adhesive process of the germ. Leb constitutes an adhesin, and differences exist in the Le compositions of adherent and nonadherent bacteria. This, perhaps, accounts for a relationship between adhesion and Le expression. Hage and colleagues identified the BabA protein (Blood group antigen-binding Adhesin) in H pylori that interacts with gastric mucus binding Leb antigens, confirming the relationship.[5] As a consequence, H+ bridges may be formed, strongly anchoring the bacterium to the gastric mucosa.

In addition, any Le antigen shows phase variation leading to the spontaneous and random switching on and off of the expression of these antigens. For example, the H-type I antigen seems to be the result of a reversible singular nucleotidic deletion/insertion in a tract of a glycosyl transferase gene. The LPS of the H pylori also seems to influence tumoral proliferation of ECL cells, stimulating the intracellular polyamine biosynthesis pathway and ornithine decarboxylase activity by the activation of a CD14 receptor on the ECL cell.

In 1997, Tomb and coworkers completely sequenced the H pylori genome, and some differences were found in gene encoding factors that are likely to interact with the host, such as surface proteins.[6] Two of the most important genes of H pylori are VACA and CAGA. The VACA gene codes for the Vac-A cytotoxin, a vacuolating toxin. Most H pylori strains (60%), by unexplained causes, do not produce this protein. The CAGA gene codes for the Cag-A protein, which seems to stimulate the production of chemotactic factors for the neutrophils by the gastric epithelium of the host. A certain proportion of H pylori strains (40%), by unexplained causes, does not produce this protein.

After the exposure to CAGA -positive H pylori strains, an increase in catalase, glutathione peroxidase, and superoxide dismutase activity has been reported. This increase is associated with fewer DNA adducts and reduced susceptibility of the gastric cells to the irreversible injuries from reactive oxygen species (ROS) compared with exposure to CAGA -negative H pylori strains. Such alterations of the ROS scavenging enzymes may partly account for the increased risk of gastric cancer in individuals with H pylori infection.

A relationship among CAGA/Cag-A, VACA alleles, and the Le subtype of H pylori strains has been reported, as has a link between these and the redox status of the gastric mucosa. For example, H pylori is able to induce apoptosis in epithelial cells and T lymphocytes. The CAGA -positive strains of H pylori seem to be able to increase FASL expression in T lymphocytes (up-regulation of FASL on such cells is redox-sensitive), which facilitates a selective killing of the T lymphocytes. This molecular mechanism may have a key role in the persistence of CAGA -positive strains.

In addition, H pylori up-regulates caspases 3, 6, 8, and 9. Caspases 3 and 9 in epithelial cells are fundamental in inducing apoptosis. The expression of some bacterial genes is acid-regulated, as reported for the FILA gene (responsible for the H pylori motility) that codes for a sigma factor required for transcription of the flagellin gene FLAA.[7] Flagella and urease are very important for the colonization of the gastric mucosa by the bacterium.

Note the following:

• H pylori infection causes atrophic and even metaplastic changes in the stomach.

• The bacterial adhesion appears to result in tyrosine phosphorylation and is specific for gastric cells.

• The adhesion of H pylori to the gastric cells causes a direct decrease in the mucosal levels of glutathione, a fundamental molecule in the maintenance of the cellular redox status and in the molecular regulation of host immune responses. However, the LPS of H pylori may induce the production of autoantibodies that are able to worsen the atrophy in the corpus mucosa and cause a concomitant increase in parietal cell antibodies. Such events are accompanied by a decrease in anti-H pylori immunoglobulin titers. This process leads to a scenario of severe atrophy without bacterial colonization combined with high levels of autoantibodies against gastric parietal cells.

• A number of reports show the close association between H pylori infection and low-grade gastric MALTomas.

• Giannakis and colleagues demonstrated that H pylori may adapt to gastric stem cells, influencing their biology and contributing to tumorigenesis of the stomach.[8]

United States statistics

The frequency of H pylori infection may be linked to race and low socioeconomic status. White persons account for 29% of cases, and Hispanic persons account for 60% of cases.

International statistics

H pylori is a ubiquitous organism. At least 50% of all people are infected,[9] but an exact determination is not available, mostly because precise data are not available from developing countries. H pylori may be detected in approximately 90% of individuals with peptic ulcer disease; however, less than 15% of infected persons may have this disease.

Race-, sex-, and age-related statistics

The pathogenetic role of H pylori may differ depending on the geography and race. White persons are infected with H pylori less frequently than persons of other racial groups. The prevalence rate is approximately 20% in white persons, 54% in African American persons, and 60% in Hispanic persons.

No sex predilection is known; however, females have a higher incidence of reinfection (5%-8%) than males.

H pylori infection may be acquired at any age. According to some epidemiologic studies, this infection is acquired most frequently during childhood. Children and females have a higher incidence of reinfection (5%-8%) than adult males.

The prognosis is usually excellent, even in patients with complications, such as gastric MALToma. However, the prognosis becomes poor for patients who develop squamous cell esophageal cancer or gastric carcinoma.

The rate of reinfection is very low (1%-2%); however, children and females have a higher incidence of reinfection (5%-8%)

Mortality/morbidity

The mortality rate related to H pylori infection is not precisely known, but it seems to be minimal (ie, approximately 2%-4% of all infected people). Mortality is due to the complications of the infection, such as gastric ulcer perforation or MALTomas of the GI tract. Otherwise, the morbidity of H pylori infection can be very high.

Results from a recent meta-analysis by Lender and colleagues suggest that the reduction of H pylori infection in developed nations may be contributing to the rise in obesity in those countries. Using 49 studies, with data from 10 European nations, Japan, the United States, and Australia, the investigators found a significant inverse correlation between the rates of obesity/overweight and the prevalence of H pylori infection. Mean rates for obese and overweight individuals were 46.6% and 14.2%, respectively, whereas the mean prevalence of H pylori infection was 44.1% (range, 17%–75%). The authors acknowledge, however, that the study does not prove that the reduced prevalence of H pylori has directly impacted obesity rates. The association, they admit, could be more complex; it may be, for example, that hygiene factors that encourage H pylori infection may also somehow discourage obesity.[10, 11]

Complications include the following:

• Gastric adenocarcinoma is the most severe consequence of an H pylori infection.

• Gastric MALToma may be treated with H pylori eradication therapy and has a better prognosis than gastric adenocarcinoma. A significant difference exists between the therapeutic response of MALTomas restricted to the mucosa and other, more infiltrating lesions. The only predictive factor for disease regression seems to be the absence of nodal involvement.

• H pylori infection is associated with squamous cell esophageal cancer.

• H pylori may play an important role in idiopathic thrombocytopenic purpura. This is due to anti-CagA antibodies that cross-react with platelet antigens.

• According to some reports, H pylori eradication may cause peptic esophagitis, probably due to a protective action of the bacteria on the cardia area.

Educate patients with a high risk for gastric cancer about clinical control methods and, if H pylori-positive, to begin eradication therapy. However, eradication regimens for H pylori are complex and might not be fully comprehended by patients; thus explore barriers to adherence and address these prior to prescribing therapy.[12] Explain the rationale for therapy, dosing instructions, expected adverse events, and the importance of completing the full therapeutic course.[12] It is crucial to educate patients about the adverse effects of the therapy to impress upon them the importance of compliance with the full regimen to prevent antibiotic resistance and relapse.

History

In the authors' opinion, there are no significant differences in the presence and frequency of symptoms, such as nausea, vomiting, pain, heartburn, or diarrhea, in patients who are infected with H pylori and those who are not. No definite evidence demonstrates a clear relationship between the symptoms of the H pylori-associated gastritis and abdominal pain or dyspeptic symptoms from other conditions, although H pylori gastritis is the cause of dyspepsia in a subset of patients (as when successful H pylori eradication results in sustained symptomatic remission) and is considered a distinct entity.[1, 13] In infected patients, 30%-35% have no symptoms.

Adults and children differ in the immune response to H pylori infection. This is probably due to a physiologic lower density of neutrophils and T lymphocytes during childhood, especially in children younger than 8 years.

Although H pylori infection is not significantly related to recurrent abdominal pain, weekly pain is reported more often in children who are infected with H pylori compared with children who are not infected.

Physical examination

No specific clinical signs have been described in patients with H pylori infection. Patients may feel dyspepsia or abdominal discomfort, such as during gastritis or with epigastric pain (eg, duodenal ulcers). In some cases, patients may feel hungry in the morning and may have halitosis.

H pylori gastritis should be categorized on the basis of gastric subsites not only because the risks of gastric cancer and peptic ulcer are affected by gastritis patterns but also because such characterization is key in identifying those who remain at high risk following eradication of H pylori (as defined by the extent and severity of the atrophy) and should thereby undergo regular endoscopic and histologic follow-up.[1]

In addition to recommendations that H pylori gastritis be categorized by gastric subsites, it is also advised that H pylori gastritis should be categorized on the basis of histology (extent/severity of inflammation/atrophy) owing to the risk of development of gastric cancer.[1] Moreover, gastric erosions should not only be reported separately from gastritis but the etiology, natural history, and clinical significance of gastroduodenal erosions should also be evaluated.

Noninvasive diagnostic studies include the carbon 13 urea breath test (UBT), fecal antigen test, and serologic parameters (pepsinogen I and II, H pylori antibody) as surrogate markers of H pylori gastritis and as indicators of gastritis severity.[1, 9]

Patients with new peptic ulcer disease should have a carbon 13 UBT, they should be tested for antibody titers, or they may require an investigation for stool antigens.

H pylori fecal antigen test

This novel rapid test is based on monoclonal antibody immunochromatography of stool samples. The test has been reported to be very specific (98%) and sensitive (94%). The results are positive in the initial stages of infection and can be used to detect eradication after treatment.

Although the H pylori fecal antigen test is an interesting tool, information about the cost of the test is pending.

Carbon 13 urea breath test

The carbon 13 UBT is based on the detection of the products created when urea is split by the organism.

Patients are asked to drink urea (usually with a beverage) labeled with a carbon isotope (carbon 13 or carbon 14). After a certain duration, the concentration of the labeled carbon is measured in the breath. The concentration is high only when urease is present in the stomach. Because the human stomach does not produce urease, such a reaction is possible only with H pylori infection.

The breath test is expensive but is becoming increasingly more available. Other problems include false-negative results due to infection with coccoid forms of H pylori that do not produce as much urease or the use of antibiotics, bismuth, histamine 2 (H2) blockers, or proton pump inhibitors.

H pylori serology

The serology test has a high (>90%) specificity and sensitivity. It is currently based on the quantitation of immunoglobulin G antibodies against H pylori by the means of an enzyme-linked immunosorbent assay.

It is useful for detecting a newly infected patient, but it is not a good test for follow-up of treated patients because the results do not indicate present infection with H pylori. The antibody titer may remain elevated for a long time after H pylori eradication. The number of false-positive results is age related and increases with age.

Antibiogram

In geographic areas with a high resistance rate against metronidazole and clarithromycin, culture for antibiotic susceptibility testing (antibiogram) seems to be useful.[3, 4] Alternatively, metronidazole and clarithromycin should not be recommended as first-line drugs in such areas.

Imaging studies are generally not helpful in the diagnosis of H pylori infection. Otherwise, they may be useful in patients with complicated disease (eg, ulcer disease, gastric cancer, MALToma). Advanced endoscopy with clinicians properly trained in image-enhanced modalities (eg, chromoendoscopy, high-resolution magnification endoscopy) and magnification provides a high degree of diagnostic accuracy for gastritis, even before histologic confirmation, as well as for atrophic mucosa and intestinal metaplasia.[1]

Esophagogastroduodenoscopy

In patients with prior peptic ulcer disease, an esophagogastroduodenoscopy (EGD) with biopsy and histological studies may be performed. Also, a carbon 13 urea breath test (UBT) is helpful in these patients.

An EGD is often necessary in patients with symptoms of peptic ulcer disease in order to view the condition of the mucosal lining of the stomach and duodenum and to obtain biopsy specimens from the gastric antrum and corpus.

An echography associated with an EGD is mandatory in patients with biopsy results that are positive for gastric MALTomas in order to allow a more precise staging of the disease.

Histologic examination

Biopsy sampling of both the antrum and corpus is required for histologic accuracy in the evaluation of gastritis.[1]

Peptic ulcer disease and gastric cancer may manifest with the same symptoms, and the only way to differentiate them is to view the lesion and to perform a histologic examination of the biopsy specimens.

H pylori is a gram-negative bacterium. It produces urease, has a spiral-like conformation, and is microaerophilic and motile because of the flagella. Flagella and urease are very important for its colonization of the gastric mucosa. Urease neutralizes gastric acidity, converting the gastric urea to ammonium ions, and flagella help the bacterium pass from the acidic gastric lumen into the mucus lining of the stomach. Two of the most important genes of H pylori are VACA and CAGA. The VACA gene codes the Vac-A cytotoxin, a vacuolating toxin, and the CAGA gene codes for Cag-A protein, which seems to stimulate the production of chemotactic factors for the neutrophils by the gastric epithelium of the host.

Biopsy specimens from esophagogastroduodenoscopy (EGD), stained with Giemsa stain, usually demonstrate a variable number of H pylori organisms adhering to the gastric epithelium, both coating the gastric wall and lining the gastric glands. The mucous film appears to be decreased. A large inflammatory infiltrate is present, with lymphocytes, neutrophils, and a variable number of mast cells that seem to play an important role in the pathogenesis of the gastric injury in persons infected with H pylori.[14, 15] Other stains are Genta, Warthin-Starry silver, and the classic hematoxylin and eosin. A rapid urease test may demonstrate the presence of H pylori in the gastric mucosa obtained by endoscopic mucosal biopsy. Bacterial culture is very difficult. It is not used for diagnosis; it is used in patients with resistant infection and for experimental and research purposes.

Although a staging system for the H pylori infection does not exist, some steps in the disease process are well described. The first step is chronic gastritis, followed after a time by the second step, atrophic gastritis. The third step is intestinal metaplasia, which may evolve into dysplasia. The last step is gastric adenocarcinoma. This process is very slow and may stop at any step because gastric cancers undoubtedly require several other factors to develop, not only an H pylori infection. As reported above, ultrasonography and esophagogastroduodenoscopy should be considered in patients with gastric MALTomas in order to allow a more precise staging of the disease.

The risk of gastric cancer is correlated with the severity and extent of atrophic gastritis; histologic staging systems can aid in risk stratification (eg, the operative link for gastritis assessment [OLGA] and operative link for gastric intestinal metaplasia assessment [OLGIM] staging systems).[1]

Selected 2021 American Gastroenterological Association (AGA) best practices

Antibiotic resistance is typically the cause of refractory H pylori infection (ie, persistent infection following attempted eradication therapy).[12] Try to ascertain potential contributing causes, such as inadequate adherence to therapy and insufficient gastric suppression.

Thoroughly review prior antibiotic exposures.[12] In the setting of any history of treatment with macrolides or fluoroquinolones, avoid clarithromycin- or levofloxacin-based regimens, respectively, owing to the greater possibility of resistance. However, consider amoxicillin, tetracycline, and rifabutin as subsequent therapies in refractory H pylori infection as resistance to these antibiotics is rare.

Adjunct therapies, including probiotics, have been proposed, but they are considered experimental as their benefits remain unproven for treating refractory H pylori infection.[12]

2020 World Society of Emergency Surgery (WSES) guidelines

Perforated and bleeding peptic ulcer clinical practice guidelines were released in January 2020 by the WSES. Indications for antimicrobial therapy and for H pylori testing in patients with bleeding peptic ulcer are as follows[16] :

• Empirical antimicrobial therapy not recommended
• H pylori testing in all patients
• If positive for H pylori, eradication therapy recommended
• First-line eradication therapy: Standard triple therapy (ie, amoxicillin, clarithromycin, proton-pump inhibitor [PPI])
• First-line therapy if high clarithromycin resistance detected: Ten-day sequential therapy with four drugs (ie, amoxicillin, clarithromycin, metronidazole, PPI)
• Second-line therapy if first-line failed: Ten-day levofloxacin-amoxicillin triple therapy
• Start standard triple therapy after 72-96 hours of intravenous PPI, for 14-day duration

Only treat patients who have a positive test result for H pylori infection. The optimal timing of H pylori eradication in asymptomatic persons is during the period when the mucosal damage remains nonatrophic.[1]

Carefully educate patients regarding the importance of completing the prescription and about the potential adverse effects of the medications.[1, 12] Importantly, consider possible antibiotic resistance when selecting the treatment regimen. Note that surgery is not required for patients with H pylori infection, but it may be considered in patients with severe complications, such as cancer.

The US Food and Drug Administration has approved several regimens, which are accepted internationally, for the treatment of H pylori infection in patients with peptic ulcer disease, both gastric and duodenal. These regimens are also known as triple therapies and have reported cure rates from 85% to 90%. Unfortunately, with the increasing rise in antimicrobial resistance, there has been an associated increase in the failure rate of standard triple therapy for H pylori infection.[17] Thus eradication regimens should be based on the best locally effective regimen, optimally with the use of individual susceptibility testing or community antibiotic susceptibility, or data regarding antibiotic use and clinical outcomes.[1, 18]

It is recommended that the outcome of eradication therapy (test for cure) always be evaluated, with noninvasive means preferred.[1]

Macrolide resistance in patients with H pylori infection is an important problem. Although the molecular mechanisms of nitroimidazole resistance are very complex and still unclear, resistance has been shown to be due to a single point mutation (usually in the RDXA gene, although other genes may also be involved, eg, FRDXA) in 1 of 4 positions of the bacterial 23S rDNA. Such mutations also determine cross-resistance to other macrolides.

2021 American Gastroenterological Association (AGA) recommendations

As noted earlier, the American Gastroenterological Association (AGA) advises that in the setting of any history of treatment with macrolides or fluoroquinolones, avoid clarithromycin- or levofloxacin-based regimens, respectively, because of the higher risk of resistance.[12] Consider amoxicillin, tetracycline, and rifabutin as subsequent therapies in refractory H pylori infection as resistance to these antibiotics is rare.

The AGA advises that if first-line therapy with bismuth quadruple therapy is ineffective, clinicians and patients should jointly decide on the selection of second-line options between (a) levofloxacin- or rifabutin-based triple-therapy regimens with a high-dose dual proton pump inhibitor (PPI) and amoxicillin, and (b) an alternative bismuth-containing quadruple therapy.[12]

When using metronidazole-containing regimens, consider adequate dosing of metronidazole (1.5–2 g daily in divided doses) with concomitant bismuth therapy to improve success of eradication therapy.

If there is no history of anaphylaxis, consider penicillin allergy testing in patients who have been labeled as having this allergy to delist penicillin as an allergy and potentially enable its use. Use amoxicillin at a daily dose of at least 2 g divided three or four times per day to avoid low trough levels.

Because inadequate acid suppression is associated with H pylori eradication failure, consider using high-dose and more potent PPIs, PPIs not metabolized by CYP2C19, or potassium-competitive acid blockers, if available, in patients with refractory H pylori infection.

Higher eradication success is achieved with longer treatment durations relative to those of shorter durations (eg, 14 days vs 7 days). Thus, as appropriate, choose longer treatment durations for treating refractory H pylori infection.

Shared decision making regarding ongoing attempts to eradicate H pylori may be appropriate in some settings. Carefully evaluate the potential benefits of H pylori eradication against potential adverse effects and the inconvenience of repeated antibiotic exposure and high-dose acid suppression, particularly in vulnerable populations (eg, elderly).

In the setting of two failed therapies with confirmed patient adherence, consider H pylori susceptibility testing to guide the selection of subsequent regimens.

It is essential to collect local data on H pylori eradication success rates for each regimen, as well as patient demographic and clinical factors (including prior non-H pylori antibiotic exposure). Make aggregated data publicly available to guide local selection of H pylori eradication therapy.

Other considerations

An emerging and increasing problem in many Western countries is the fact that some H pylori strains in children are resistant to the antibiotic clarithromycin.[19] The causes are not known.

All the eradication treatments have a high incidence of certain adverse effects (eg, nausea, metallic taste). If skin rash, vomiting, or diarrhea occurs, discontinue the treatment.

The links between H pylori and nonulcer dyspepsia are debated; however, some patients with nonulcer dyspepsia benefit from eradication. Indeed, H pylori eradication is the first-line and preferred treatment for H pylori -infected dyspeptic individuals.[1] Patients with symptoms have a higher eradication rate than patients with nonulcer dyspepsia disease. Eradication of H pylori in patients without peptic ulcer disease has resolved the dyspepsia in a few cases. If successful H pylori eradication does not resolve dyspeptic symptoms, patients should be considered to have "functional dyspepsia."[1]

Diet and activity

No dietary restrictions are usually needed, and no limitations of physical activity are needed if patients do not have complications.

Posttreatment monitoring

Consider performing a urea breath test (UBT) 4-12 weeks after the end of treatment. An esophagogastroduodenoscopy (EGD) with biopsy and a urease test also may be useful, but, importantly, remember that this test does have a significant rate of false-negative results.

Searching and screening for H pylori gastritis depends on the epidemiologic setting and is appropriate at an age before the onset of atrophic gastritis and intestinal metaplasia.[1]

Note that the risk of gastric cancer is increased in patients who have an H pylori infection and whose first-degree relatives have a history of gastric cancer, even if they are asymptomatic. Thus, eradicating H pylori reduces the risk of gastric cancer; the risk reduction relies on the presence, severity, and extent of atrophic damage at the time of eradication.[1]

Persons emigrating from geographic areas with a high incidence of gastric cancer have an increased risk.

Consider any patient with precancerous lesions of the stomach (ie, intestinal metaplasia) for treatment of H pylori infection.

The goals of pharmacotherapy are to eradicate the microorganism, to prevent complications, and to reduce morbidity. Triple therapies are used.

Increasing resistance to antibiotics has made alternative treatments necessary. Antibiotic resistance phenomena are now observed with a certain frequency in H pylori infections; occasionally, even after the use of different eradicating protocols, H pylori is not eradicated.[20, 21] In such cases treatment with rifabutin may be indicated.

On April 1, 2020, the US Food and Drug Administration (FDA) recommended the immediate withdrawal of ranitidine from the market based on findings of unacceptable levels of N-Nitrosodimethylamine (NDMA), a possible carcinogen.[22] In July, 2021, the original report was retracted at the request of the authors.[23] The FDA may consider allowing ranitidine products back on the market if they are proven stable during storage and NDMA amounts do not increase to unsafe levels over time.[24, 25]

Several studies are underway to elucidate the role of nanotechnology in the treatment of H pylori infection using nanoparticles synthesized with antibiotics or other agents.[26, 27, 28, 29]

Class Summary

The approved antidiarrheal for this infection is bismuth subsalicylate. It has both antisecretory and antimicrobial activity.

Bismuth subsalicylate (Bismatrol, Pepto-Bismol)

Has cytoprotective effect on the GI mucosa, probably due to the stimulation of prostaglandin production and modulation of the immune response. In addition, it has been demonstrated that some deposits (probably bismuth salts) appear on both surfaces of the cell wall of H pylori after H pylori</i> from antral epithelium.

Class Summary

Use agents known to be effective against H pylori.

Metronidazole (Flagyl)

Reduced to its active form intracellularly only by anaerobic organisms, then disrupts the helical structure of DNA and inhibits bacterial nucleic acid synthesis.

Tetracycline (Sumycin)

Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit(s).

Clarithromycin (Biaxin)

Inhibits bacterial growth, possibly by blocking the dissociation of peptidyl tRNA from ribosomes, causing the arrest of RNA-dependent protein synthesis.

Amoxicillin (Amoxil, Trimox)

Inhibits the final stage of bacterial cell wall synthesis by binding to specific PBPs on the inner part of the bacterial wall, leading to bacterial lysis.

Class Summary

Bind to proton pump of parietal cells, inhibiting the secretion of hydrogen ions into the gastric lumen. Relieve pain and heal peptic ulcers more rapidly than H2 antagonists.

Lansoprazole (Prevacid)

Works by inhibiting the H+/K+ -ATPase enzyme system of the gastric parietal cells.

Omeprazole (Prilosec)

Decreases gastric acid secretion by inhibiting parietal cell H+/K+ -ATP pump.

Class Summary

Reversible competitive blockers of histamine at H2 receptors, particularly those in the gastric parietal cells, wherein they inhibit acid secretion. H2 antagonists are highly selective, do not affect the H1 receptors, and are not anticholinergic agents. Proton pump inhibitors are usually preferred.

Ranitidine (Zantac)

Reduces basal and nocturnal gastric acid secretion by competitive inhibition of binding of histamine to receptors (H2 receptor) on the gastric parietal cells. Although not effective as single agents for the eradication of H pylori, appears to increase the systemic absorption of bismuth subsalicylate.

Famotidine (Pepcid)

Competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Class Summary

Combinations allow ease of administration and promote enhanced patient adherence.

Amoxicillin/omeprazole/rifabutin (Talicia)

Combination delayed-release capsules contains amoxicillin, omeprazole, and rifabutin is administered as an every 8 h regimen. It is indicated for treatment of H pylori infection in adults.

Lansoprazole/amoxicillin/clarithromycin (Prevpac)

Copackaged product containing a PPI, a macrolide antimicrobial, and a penicillin class antibacterial as a twice-daily regimen. Indicated for H pylori eradication to reduce the risk of duodenal ulcer recurrence. 

Omeprazole/amoxicillin/clarithromycin (Omeclamox-Pak)

Copackaged product containing a PPI, a macrolide antimicrobial, and a penicillin class antibacterial. It is indicated for treatment of patients with H pylori infection and duodenal ulcer disease (active or up to 1-year history) to eradicate H pylori. It is a twice-daily regimen.