Helicobacter Pylori Infection 

Updated: Oct 10, 2019
Author: Luigi Santacroce, MD; Chief Editor: BS Anand, MD 

Overview

Practice Essentials

Helicobacter pylori (see the image below) is a ubiquitous organism that is present in about 50% of the global population. Chronic infection with H pylori causes atrophic and even metaplastic changes in the stomach, and it has a known association with peptic ulcer disease.[1] The most common route of H pylori infection is either oral-to-oral or fecal-to-oral contact.[2]

An antral gland of the stomach with a large Giemsa 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.

Signs and symptoms

In general, patients infected with H pylori are asymptomatic, and no specific clinical signs and symptoms have been described. When signs and/or symptoms are present, they may include the following:

  • Nausea

  • Vomiting

  • Abdominal pain

  • Heartburn

  • Diarrhea

  • Hunger in the morning

  • Halitosis (bad breath)

See Presentation for more detail.

Diagnosis

Testing

In patients with suspected H pylori infection, the following laboratory studies may aid in the diagnosis:

  • H pylori fecal antigen test: Very specific (98%) and sensitive (94%); positive results obtained in the initial stages of infection; can be used to detect posttreatment eradication

  • Carbon-13 urea breath test: Concentration of the labeled carbon is high in breath only when urease is present in the stomach, a reaction possible only with H pylori infection

  • H pylori serology: High (>90%) specificity and sensitivity; useful for detecting a newly infected patient but not a good test for follow-up of treated patients

  • Antibiogram: Useful in geographic areas with a high resistance rate against metronidazole and clarithromycin[3, 4] ; these antibiotics should not be recommended as first-line drugs in such areas

Staging

There is no staging system for H pylori infection, but the following steps in the disease process are well described:

  • Chronic gastritis

  • Atrophic gastritis

  • Intestinal metaplasia: May evolve into dysplasia

  • Gastric adenocarcinoma: Consider ultrasonography and esophagogastroduodenoscopy (EGD) in patients with gastric MALTomas (mucosa-associated lymphatic tissue lymphomas) for more precise staging of the disease

Imaging studies

Imaging studies are not helpful in the diagnosis of H pylori infection. However, they may be useful in patients with complicated disease (eg, ulcer disease, gastric cancer, MALToma).

Procedures

  • EGD: Often necessary in patients with symptoms of peptic ulcer disease to view the condition of the mucosal lining of the stomach and duodenum

  • Biopsy plus EGD: To obtain biopsy specimens from the gastric antrum and corpus and to perform a histologic examination on the obtained specimens

  • Echography plus EGD: Mandatory in patients with positive biopsy results for gastric MALTomas to allow a more precise staging of the disease

See Workup for more detail.

Management

Only treat patients with a positive test result for H pylori infection. It is important to consider possible antibiotic resistance when selecting the treatment regimen.

Pharmacotherapy

The US FDA and international organizations have approved several triple therapy regimens for the treatment of H pylori infection in patients with gastric and duodenal peptic ulcer disease, as follows:

  • Omeprazole, amoxicillin, and clarithromycin (OAC) for 10 days

  • Bismuth subsalicylate, metronidazole, and tetracycline (BMT) for 14 days

  • Lansoprazole, amoxicillin, and clarithromycin (LAC), for either 10 days or 14 days

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

Other medications used in the management of H pylori infection include the following:

  • Antidiarrheals (eg, bismuth subsalicylate)

  • Proton pump inhibitors (eg, lansoprazole, omeprazole)

  • H2-receptor blockers (eg, ranitidine, famotidine)

Surgical option

Surgical intervention is not required for patients with H pylori infection, but it may be a consideration for patients with severe complications, such as cancer.

See Treatment and Medication for more detail.

Background

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.

An antral gland of the stomach with a large Giemsa 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. Lamina propria of t Helicobacter pylori infection. Lamina propria of the stomach is shown with 2 mast cells overlapping each other. Note the upper part shows 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 peptic ulcers 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.

Pathophysiology

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.

Etiology

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 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]

Epidemiology

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 exact 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.

Prognosis

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.

Patient Education

Educate patients with a high risk for gastric cancer about clinical control methods and, if H pylori -positive, to begin eradication therapy. However, patients must be educated about the adverse effects of the therapy in order to impress upon them the importance of compliance with the full regimen in order to prevent antibiotic resistance and relapse.

 

Presentation

History

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, 12]  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.

 

DDx

 

Workup

Approach Considerations

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.

Laboratory Studies

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.

Other Tests

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.

Histologic Findings

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.[13, 14] 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 purposes.

Staging

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]

 

Treatment

Medical Care

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] 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 now 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%-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.[15]  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, 16]

Administer triple therapies for 10-14 days. The treatment regimens are omeprazole, amoxicillin, and clarithromycin (OAC) for 10 days; bismuth subsalicylate, metronidazole, and tetracycline (BMT) for 14 days; and lansoprazole, amoxicillin, and clarithromycin (LAC), which has been approved for either 10 days or 14 days of treatment.

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

A trial of empiric therapy for H pylori infection in 7 Latin American sites found higher eradication rates with 14 days of standard triple therapy (LAC) than with shorter 4-drug therapies. Neither 5 days of concomitant lansoprazole, amoxicillin, clarithromycin, and metronidazole nor 10-day sequential treatment (5 days of LA, then 5 days of LCM) was significantly better than the standard therapy at any site.[17]

H pylori eradication rates were higher for a 7-day antibiotic regimen containing lansoprazole, amoxicillin, and clarithromycin (LAC), when used as first-line therapy compared with levofloxacin, amoxicillin, and lansoprazole (LAL).[18] Additionally, LAC did not achieve a higher rate of eradication than LAL as second-line therapy; thus, consideration of the sequence of administering antibiotic regimens for H pylori is important.

Hsu et al reported that the 7-day concomitant therapy is superior to the 7-day standard triple therapy for H pylori eradication, and it is also simpler to administer than the 10-day sequential therapy, because the drugs are not changed halfway through the treatment course.[15] Similarly, Apostolopoulos et al reported that the 10-day concomitant quadruple therapy resulted in statistically significant higher eradication of H pylori than 10-day sequential quadruple therapy in an area of Greece with a greater than 20% local resistance to clarithromycin.[19]

A study by Yoon et al investigated the efficacy of a moxifloxacin-containing triple therapy as second-line therapy for H pylori infection as well as the effect of treatment duration and antibiotic resistance on the eradication rate.[20] In 2004, 41 patients who had persistent H pylori infection were given a 7-day course of 400 mg qd moxifloxacin, 1000 mg bid amoxicillin, and 20 mg bid esomeprazole; the intention-to-treat (ITT) rate was 75.6% with a per-protocol (PP) eradication rate of 83.8% and a moxifloxacin resistance rate of 5.6%. During 2005-2006, 139 patients were treated to a 10-day course of this regimen, with an ITT rate of 71.9%, PP eradication rate of 82.6%, and moxifloxacin resistance rate of 12%. One-hundred eight-one patients treated in 2007-2008 received a 14-day triple-therapy regimen: ITT rate, 68%; PP eradication rate, 79.9%; moxifloxacin resistance rate: 28.2%.[20]

Despite the increased duration of treatment in each successive group of patients, there was no statistical difference in efficacy among the 3 treatment groups.[20] The investigators attributed the low eradication rate despite increased duration of therapy to a coincident, marked increase in moxifloxacin resistance and concluded that when rapid antibiotic resistance occurs, tailored treatment based on antibiotic susceptibility testing may achieve higher eradication rates.[20]

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.

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.[21] 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.

Prevention

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.

 

Medication

Medication Summary

The goals of pharmacotherapy are to eradicate the microorganism, to prevent complications, and to reduce morbidity. Triple therapies are used. Worldwide, accepted treatment regimens are BMT, LAC, and OAC. BMT regimen is based on the administration of bismuth subsalicylate, metronidazole, and tetracycline. Add an H2-receptor antagonist for an additional 4 weeks. LAC regimen is based on the administration of lansoprazole, amoxicillin, and clarithromycin. OAC regimen is based on the administration of omeprazole, amoxicillin, and clarithromycin.

Increasing resistance to antibiotics has made alternative treatments necessary. In a phase 3 trial conducted by Malfertheiner et al, quadruple therapy (omeprazole plus a single 3-in-1 capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline) was tested against standard therapy in adults with H pylori infection.[22] This study suggests quadruple therapy provides superior eradication with similar safety and tolerability to standard therapy.

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.[23, 24, 25, 26]

As noted, 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.[27, 28] In such cases treatment with rifabutin may be indicated.

Antidiarrheals

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.

Antibiotics

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.

Proton pump inhibitors

Class Summary

Bind to proton pump of parietal cell, 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.

H2 receptor blockers

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.

 

Questions & Answers

Overview

What is Helicobacter pylori (H pylori)?

What are the signs and symptoms of Helicobacter pylori (H pylori) infection?

Which lab studies are used in the diagnosis of Helicobacter pylori (H pylori) infection?

How is Helicobacter pylori (H pylori) infection staged?

What is the role of imaging studies in the diagnosis of Helicobacter pylori (H pylori) infection?

Which procedures are performed in the evaluation of Helicobacter pylori (H pylori) infection?

What are considerations regarding the treatment of Helicobacter pylori (H pylori) infection?

What is the FDA approved therapy regimen for the treatment of Helicobacter pylori (H pylori) infection and what are the adverse effects?

Which medications are used in the management of Helicobacter pylori (H pylori) infection?

When is surgery indicated in the treatment of Helicobacter pylori (H pylori) infection?

When was Helicobacter pylori (H pylori) infection first identified?

Which extragastric diseases is Helicobacter pylori (H pylori) infection associated with?

What is the association between Helicobacter pylori (H pylori) infection, and malignancies?

In which counties does Helicobacter pylori (H pylori) infection occur more frequently?

What is the significance of Helicobacter-like organisms (HLOs) in the study of Helicobacter pylori (H pylori) infections?

How is Helicobacter pylori (H pylori) infection transmitted?

What is the pathophysiology of Helicobacter pylori (H pylori) infection in a susceptible host?

What is an alternative hypothesis of the pathophysiology of Helicobacter pylori (H pylori) infection?

What is the role of genetics in the pathogenesis of Helicobacter pylori (H pylori) infection?

What is the pathogenesis of Helicobacter pylori (H pylori) infection?

What is the global prevalence of Helicobacter pylori (H pylori) infection?

How does the incidence of Helicobacter pylori (H pylori) infection vary by age?

What are the racial predilections of Helicobacter pylori (H pylori)?

How does the prevalence of Helicobacter pylori (H pylori) infection vary among racial groups?

How does the incidence of Helicobacter pylori (H pylori) infection vary by sex?

What is the prognosis of Helicobacter pylori (H pylori) infection?

What is the mortality rate for Helicobacter pylori (H pylori) infection?

What is the morbidity of Helicobacter pylori (H pylori) infection?

What are possible complications of Helicobacter pylori (H pylori) infection?

What information about Helicobacter pylori (H pylori) infection should patients receive?

Presentation

What is the role of clinical history in the evaluation of Helicobacter pylori (H pylori) infection?

Which physical findings suggest Helicobacter pylori (H pylori) infection?

DDX

What are the differential diagnoses for Helicobacter Pylori Infection?

Workup

What is the role of lab studies in the workup of Helicobacter pylori (H pylori) infection?

What is the role of the H pylori fecal antigen test in the workup of Helicobacter pylori (H pylori) infection?

What is the role of the carbon 13 urea breath test in the workup of Helicobacter pylori (H pylori) infection?

What is the role of serology testing in the workup of Helicobacter pylori (H pylori) infection?

What is the role of antibiotic susceptibility testing (antibiogram) in the workup of Helicobacter pylori (H pylori) infection?

What is the role of imaging studies in the workup of Helicobacter pylori (H pylori) infection?

What is the role of esophagogastroduodenoscopy (EGD) in the workup of Helicobacter pylori (H pylori) infection?

How are peptic ulcer disease and gastric cancer differentiated in the evaluation of Helicobacter pylori (H pylori) infection?

Which histologic findings are characteristic of Helicobacter pylori (H pylori) infection?

What are steps in the disease progression of Helicobacter pylori (H pylori) infection?

Treatment

What should be considered prior to treatment of Helicobacter pylori (H pylori) infection?

What is the FDA approved treatment regimen for Helicobacter pylori (H pylori) infection?

What are the options for combination therapies for Helicobacter pylori (H pylori) infection?

What is the efficacy of triple therapies for Helicobacter pylori (H pylori) infection?

What causes drug-resistance in Helicobacter pylori (H pylori) infection?

What are the adverse effects of medical treatments for Helicobacter pylori (H pylori) infection?

What is the association between Helicobacter pylori (H pylori) infection and dyspepsia?

Which dietary and activity restrictions are indicated during the treatment of Helicobacter pylori (H pylori) infection?

What monitoring is needed following treatment for Helicobacter pylori (H pylori) infection?

Which patient groups are at increased risk for gastric cancer from Helicobacter pylori (H pylori) infection?

Medications

What are the goals of drug treatment for Helicobacter pylori (H pylori) infection?

Which medications are used to treat resistant Helicobacter pylori (H pylori) infection?

Which medications in the drug class H2 receptor blockers are used in the treatment of Helicobacter Pylori Infection?

Which medications in the drug class Proton pump inhibitors are used in the treatment of Helicobacter Pylori Infection?

Which medications in the drug class Antibiotics are used in the treatment of Helicobacter Pylori Infection?

Which medications in the drug class Antidiarrheals are used in the treatment of Helicobacter Pylori Infection?