Clinical Considerations for the Treatment of H pylori Infection

Release Date: December 1, 2011

Expiration Date: December 31, 2013

FACULTY:

G. Blair Sarbacker, PharmD
Assistant Professor, Pharmacy Practice
University of the Incarnate Word
Feik School of Pharmacy
San Antonio, Texas

Elizabeth Montfort, PharmD
Assistant Professor, Pharmacy Practice
University of the Incarnate Word
Feik School of Pharmacy
San Antonio, Texas

FACULTY DISCLOSURE STATEMENTS:

Drs. Sarbacker and Montfort have no actual or potential conflicts of interest in relation to this activity.

Postgraduate Healthcare Education, LLC does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

ACCREDITATION STATEMENT:

Pharmacy
acpePostgraduate Healthcare Education, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
UAN: 0430-0000-11-035-H01-P
Credits: 2.0 hours (0.20 ceu)
Type of Activity: Knowledge

TARGET AUDIENCE:

This accredited activity is targeted to pharmacists. Estimated time to complete this activity is 120 minutes.

Exam processing and other inquiries to:
CE Customer Service: (800) 825-4696 or cecustomerservice@jobson.com

DISCLAIMER:

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients' conditions and possible contraindications or dangers in use, review of any applicable manufacturer's product information, and comparison with recommendations of other authorities.

GOAL:

To review the history, epidemiology, pathophysiology, risk factors, transmission, and complications of Helicobacter pylori infection and to discuss diagnosis, pharmacologic treatment options, and the pharmacist's role.

OBJECTIVES:

After completing this activity, the participant should be able to:

  1. Identify the factors associated with increased risk and transmission of H pylori infection.
  2. Explain the potential complications of H pylori infection.
  3. Identify patients who warrant testing and treatment for H pylori infection.
  4. Differentiate between the available treatments for H pylori infection.

First detected in gastric biopsies by John Warren in 1979, Helicobacter pylori was noted to rest on the gastric epithelial cells beneath the mucous gel. Warren was subsequently able to demonstrate the relationship of these gram-negative spiral-shaped bacteria to chronic gastritis and ulcers. With the help of Barry Marshall, Warren successfully colonized the bacteria, which were first thought to belong to the Campylobacter genus because of their shape and properties. Several years later, the bacteria were reclassified as part of the Helicobacter genus. In 2005, the Nobel Prize in Medicine was awarded to Warren and Marshall for their discovery.1-4

The frequency of H pylori infection is decreasing worldwide.5-7 While it is estimated that approximately 50% of the world population is infected with H pylori, the prevalence varies from 7% to 87%.8,9 The prevalence of infection in the United States is estimated to be 30% to 40%.10 Generally, rates of infection are higher in developing countries; however, there is variation within countries.9-11 Several factors have been linked to increased risk of infection with H pylori, including age, socioeconomic status, and gender.

INFECTION RISK FACTORS AND TRANSMISSION

H pylori is typically contracted during childhood.10 Lower socioeconomic status during childhood is associated with a higher risk of H pylori infection.5 Infection prevalence increases with age, except in developing countries, where a higher prevalence is associated with younger age.7,11 A cohort effect related to the lower socioeconomic status of children in previous decades is surmised to be the reason behind the increased prevalence in older age groups.8 Socioeconomic status likely influences the methods of H pylori transmission.

Human-to-human contact has been reported to be responsible for transmission of H pylori, with a high incidence within families.9 The foremost means of transmission are believed to be the gastro-oral route (vomit) and the fecal-oral route. Some evidence supports transmission of the bacteria via contaminated food and water, although the available data are conflicting.5,12

PATHOPHYSIOLOGY

Once H pylori enters the body, several mechanisms allow it to evade attack by the immune system, including genetic diversity and bacterial mimicry.13,14 These mechanisms permit bacterial growth and survival by disarming host defense mechanisms. H pylori sustains survival in the host by disrupting epithelial-cell inflammatory signaling, which in turn modifies mucosal immune response.13 Not only does H pylori have genes that allow for adaptation to varying gastric conditions, but the high amount of urease it produces permits colonization in the stomach.14,15 The organism is protected from the acidic environment by the ammonia produced in response to the amount of urease. The high virulence exhibited by H pylori results in an increased ability to adhere to the mucosa, as well as a greater ability to manufacture potentially toxic enzymes.16 H pylori causes several complications in the host by precipitating chronic inflammation.13

CLINICAL MANIFESTATIONS

H pylori infection has been implicated in the development of gastritis, gastric and duodenal ulceration, and gastric cancer.

Gastritis

The association between H pylori and gastritis is well established, as almost all patients who contract the infection present with gastritis. Gastritis induced by H pylori results from the secretion of cytokines, which leads to inflammation. Further adding to the evidence that H pylori is responsible for the development of gastritis is the fact that gastritis is resolved through eradication of H pylori.3,10,13 Acute gastritis, which is typically acquired shortly after infection, may resolve spontaneously when the infection is eliminated. More often, acute gastritis progresses to chronic active gastritis. From here, patients may develop antrum-predominant gastritis or multifocal atrophic gastritis.

Antrum-Predominant Gastritis: Gastric acid may be elevated or normal in patients with antrum-predominant gastritis. This type of gastritis is typically associated with duodenal ulcer disease presenting with minimal to no gastric atrophy. Lymphomas are a rare complication of antrum-predominant gastritis.17

Multifocal Atrophic Gastritis: Multifocal atrophic gastritis can cause atrophy that is capable of spreading to the intestine, in turn causing intestinal-type gastric cancer with loss or lack of hydrochloric acid. Multifocal atrophic gastritis can lead to gastric ulcers and lymphomas.17

Peptic Ulcer Disease

Originally, stress and diet were considered to be the causative factors for peptic ulcer disease (PUD). H2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) were given, with no opportunity for a cure, which contributed to the high morbidity and mortality of PUD.3,16,18 H pylori has since been implicated, with an estimated 15% to 20% of infected patients developing PUD. In Western countries, however, these rates have recently fallen owing to the downward trend of infection.19 Ninety percent of non–nonsteroidal anti-inflammatory drug (NSAID)-related duodenal ulcers and 80% of non–NSAID-related gastric ulcers are caused by H pylori.18 Genetics, changes in acid secretion and gastric hormones, and the pattern of the induced gastritis are among the factors involved in H pylori–induced PUD.16

Gastric ulcers are believed to result from the mucosal damage caused by H pylori. In patients with duodenal ulcers, the duodenal mucosa is damaged by excess acid production. Excess acid is released in response to abnormal gastrin release, which is caused by gastric mucosal inflammation induced by H pylori. In non–NSAID-related ulcers, eradication of the infection has been shown to eliminate PUD in most cases.8

The 1994 National Institutes of Health Consensus Statement advises that acid-suppressive therapy be given in combination with antimicrobial treatment in patients testing positive for H pylori because of the acceleration in healing seen with simultaneous administration of these medications.3,16 H pylori eradication therapy not only is cost-effective, but it also reduces PUD recurrence. Current guidelines recommend eradication therapy in patients with PUD.10

Gastric Cancer

More prevalent in men than in women, gastric cancer is the second most common cause of cancer-related deaths in men, with a 5-year survival rate of 20%. The strongest known risk factor for gastric cancer is H pylori, which is suspected to cause the disease by allowing mucosal cells to become malignant. The chronic inflammation caused by the infection may lead to atrophic inflammatory changes in the stomach, resulting in cyclo-oxygenase-2 expression and increased prostaglandin. These changes, in addition to biochemical and morphologic alterations, are implicated in the transformation of the mucosal cells. While H pylori is a risk factor, evidence is insufficient to suggest that the eradication of H pylori prevents gastric cancer.10,20

Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

Several nonrandomized, observational, epidemiologic studies have suggested that H pylori is a causative agent for gastric MALT lymphoma. Tumor-regression rates of 60% to 90% have been noted in patients who undergo eradication therapy. Additionally, recent studies suggest that, with H pylori eradication, 5-year recurrence rates for low-grade MALT range from 3% to 13%.10

DIAGNOSIS

Routine testing of patients is not recommended because not all infected persons have active disease or complications. Testing should be reserved for patients who will require treatment in the event that the results are positive. Current guidelines recommend that patients who have or have had PUD be tested, as well as patients with gastric MALT lymphoma, uninvestigated dyspepsia, or previous resection of early gastric cancer.8,10

Testing Methods

Tests for H pylori fall into one of two categories: invasive and noninvasive.

Invasive: Invasive tests include endoscopy, the rapid urease test, histologic methods, and culture. Endoscopy aids in the diagnosis of gastritis and permits biopsy but cannot visualize H pylori, so it is used in concert with other testing methods for H pylori diagnosis. The rapid urease test permits the detection of H pylori in a biopsy. The biopsied tissue is placed into a dye that changes color, if positive, based on increased pH. The pH increases when the urease is converted to urea by the H pylori. To avoid false-negative results, patients scheduled for the rapid urease test should be instructed to avoid the use of H2RAs 24 hours prior, PPIs 2 weeks prior, and bismuth or antimicrobials 4 weeks prior to testing.8,21 A biopsy also may be tested using histologic methods, which have high sensitivity and specificity but require trained personnel, and the results can vary from observer to observer. Culture has the additional benefit of allowing for susceptibility testing. Culture has high specificity, but its sensitivity is variable.8,21

Noninvasive: The urea breath test, the stool antigen test, and serologic testing are noninvasive methods of diagnosing H pylori. When combined with citric acid pretreatment and doses of 13C-urea no less than 75 mg, the urea breath test has proven to be extremely reliable. This highly sensitive and specific test measures the amount of carbon dioxide produced by the conversion of 13C-urea by H pylori. The stool antigen test uses polyclonal or monoclonal antibodies to detect H pylori antigens; of these tests, enzyme-linked immunosorbent assay has the highest accuracy. To avoid false-negative results, patients scheduled for the urea breath test or stool antigen test should be instructed to avoid the use of H2RAs 24 hours prior, PPIs 2 weeks prior, and bismuth or antimicrobials 4 weeks prior to testing.8,21 Serologic testing uses immunoglobulin G antibodies to H pylori to detect infection. Because antibodies exist for months after H pylori eradication, serologic testing is not recommended for confirmation of eradication. The decreased use of this test is likely due to its low sensitivity and specificity.18,21

Recently updated guidelines suggest that two positive tests are needed for diagnosis of H pylori infection, except in the case of duodenal ulcer, owing to its high correlation. It is also recommended that a delayed test be performed when negative endoscopy results are obtained after an acute upper gastrointestinal bleed. The delayed test—involving either histologic methods or the urea breath test—should occur within 4 to 8 weeks of the bleed. According to the Second Asian Pacific Consensus Guidelines, the most accurate noninvasive test is the urea breath test. It is important to note that, because of manufacturer changes that may affect the dependability of this test, local validity is needed.21

TREATMENT

Established indications for the treatment of H pylori infection include active PUD, confirmed history of PUD without prior treatment for H pylori infection, low-grade gastric MALT lymphoma, prior endoscopic resection of early gastric cancer, and uninvestigated dyspepsia.

In patients with gastrointestinal bleeding, treatment of infection has been shown to reduce rebleeding by up to 17% compared with treatment for ulcer healing alone. In patients without bleeding who undergo successful H pylori eradication therapy, remission rates are approximately 97% in those with gastric ulcers and 98% in those with duodenal ulcers after 12 months.10

Eradication of H pylori is the primary goal of therapy for H pylori–positive patients with an active or previously documented ulcer.22 Eradication heals the ulcer, relieving the patient’s symptoms. A Cochrane Review found that eradication of H pylori reduces gastric and duodenal ulcer recurrence.23 In addition, a reduction in the risk of gastric cancer may be associated with H pylori eradication.11 According to the Maastricht Consensus Report, it is optimal for H pylori treatment regimens to have a minimum eradication rate of 80%.24 In addition, these regimens should minimize antimicrobial resistance.

Pharmacologic Agents

Antisecretory Drugs: H2RAs are associated with lower eradication rates, and therefore they should not be substituted for PPIs.22 The role of PPIs is to enhance antibiotic activity and stability by increasing intragastric pH.22 H pylori replicates when the PPI increases intragastric pH to 6 or more, which renders the bacterium more sensitive to amoxicillin.25 PPIs inhibit gastric-acid secretion and are most effective when taken 30 to 60 minutes prior to meals.

Antibiotics: Several antibiotics with varying characteristics are used in the treatment of H pylori. Bismuth salts have a topical antimicrobial effect.22 Amoxicillin inhibits the synthesis of the bacterial cell wall and has a low resistance rate. Clarithromycin, a macrolide and strong inhibitor of CYP3A4, binds to the ribosome and inhibits protein synthesis. It is well known that bacteria develop efflux channels for clarithromycin, preventing it from binding to the ribosome; therefore, widespread use of the drug in upper respiratory infections has led to increased clarithromycin resistance.26 Metronidazole induces DNA double-strand breaks and results in cell death. Increasing the dosage and duration of metronidazole can partially overcome drug resistance. Metronidazole inhibits CYP3A4, CYP2C9, and aldehyde dehydrogenase (ALDH). In the presence of alcohol, the inhibition of ALDH results in elevated blood acetaldehyde levels and a disulfiram reaction.25 Fluoroquinolones induce cell death by disrupting gyrase, an enzyme needed for DNA replication; however, the overuse of fluoroquinolones has led to an increase in resistance rates, reaching 20% in some areas.24,25 Tetracycline inhibits protein synthesis, and resistance rates are low. Rifabutin inhibits DNA-dependent RNA polymerase and initiation of transcription, preventing protein synthesis.

Drug Regimens to Eradicate H pylori

No single drug achieves the optimal eradication rate on its own, and most treatment regimens include two antibiotics in addition to a PPI (TABLES 1 and 2).10 Triple therapy, the most common recommendation for H pylori eradication, consists of a PPI, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily for 7 to 14 days.26 The PPIs lansoprazole (30 mg), omeprazole (20 mg), pantoprazole (40 mg), rabeprazole (20 mg twice daily), and esomeprazole (40 mg once daily) are all effective for the treatment of H pylori.10 To date, dexlansoprazole has not received an indication for H pylori eradication. Lansoprazole, amoxicillin, and clarithromycin are available as a daily administration card under the name Prevpac. In patients allergic to penicillin, metronidazole may be substituted for amoxicillin. Triple therapy originally achieved 90% eradication of H pylori; however, rates have declined to consistently under 70% to 80% in some areas. Clarithromycin resistance is thought to be the primary contributing factor.27 One meta-analysis reported a nearly 60% reduction if clarithromycin resistance was present.26

tbl1

tbl2

In areas with high (>20%) clarithromycin resistance, quadruple therapy (TABLE 2) is a possibility for initial therapy.8 Quadruple therapy consists of a PPI, bismuth 525 mg four times daily, metronidazole 250 mg four times daily, and tetracycline 500 mg four times daily for 10 to 14 days. Two combination products, Helidac and Pylera, are available. Helidac, which is taken with each meal and at bedtime for a total of four doses of each component per day, contains two bismuth subsalicylate 262.4-mg tablets, metronidazole 250 mg, and tetracycline 500 mg. Pylera contains bismuth subcitrate 140 mg, metronidazole 125 mg, and tetracycline 125 mg. This combination product reduces the number of capsules to three taken four times per day in addition to the PPI taken twice daily. The medication may be taken with each meal and at bedtime. A recent trial compared H pylori eradication with quadruple therapy for 10 days versus triple therapy with amoxicillin and clarithromycin for 7 days (instead of the preferred 14 days). The eradication rate for quadruple therapy was 93%, compared with 68% for triple therapy. Quadruple therapy should be considered as first-line therapy in areas with high clarithromycin resistance.28

Sequential therapy (TABLE 2) has been proposed as an alternative to triple therapy for an initial regimen. Sequential therapy consists of a PPI twice daily and amoxicillin 1 g twice daily for 5 days, followed by a PPI twice daily, clarithromycin 500 mg twice daily, and metronidazole twice daily for an additional 5 days. The rationale for sequential therapy is that amoxicillin rarely promotes resistance.22 Amoxicillin is used initially to reduce the bacterial load in the stomach to improve the efficacy of clarithromycin and metronidazole.26 In a meta-analysis of 10 randomized trials, sequential therapy achieved an eradication rate of 93.4% versus 76.9% for triple therapy.29 While results appear promising, the majority of data involving sequential therapy have come from one country (Italy). Studies in Thailand, Spain, and Taiwan demonstrated the efficacy of sequential therapy; however, studies from Panama, France, and Korea failed to show a significant difference between standard triple therapy and sequential therapy.30 A recent trial in Latin America compared 14-day triple therapy with 10-day sequential therapy; the eradication rate was 82.2% for triple therapy versus 76.5% for sequential therapy.31

Because antimicrobial resistance varies geographically, studies are needed to validate sequential therapy in the U.S. In addition, sequential therapy involves the simultaneous use of metronidazole and clarithromycin for H pylori eradication. Treatment failure with this regimen may lead to resistance to one or both medications and limit additional regimens for second-line treatments.27 Levofloxacin may play a role in initial treatment and is an option for second-line therapy.27 Eradication rates range from 72% to 96%; however, resistance to levofloxacin is increasing, especially in countries with a high consumption of fluoroquinolones. At this time, it is recommended that levofloxacin be used only in areas with known low resistance to fluoroquinolones.30

Eradication Confirmation

Confirmation of eradication of H pylori infection is recommended in patients who have undergone resection for early gastric cancer, in those who have had an H pylori–associated ulcer or gastric MALT lymphoma, and in patients whose symptoms persist after treatment.8 A urea breath test or fecal antigen test may be used to confirm eradication at least 4 weeks after completion of therapy.8 PPIs must be discontinued prior to a urea breath test to prevent a false-positive result.16 The urea breath test has demonstrated 94% sensitivity and 95% specificity; the stool antigen test is less sensitive and specific.24 Endoscopy is an alternative means of confirming eradication. Once H pylori has been eradicated, it is unnecessary to continue antisecretory maintenance therapy for prevention of recurrent bleeding from peptic ulcers.32

Management of Treatment Failure

Failure of H pylori eradication therapy is suggested when symptoms persist or recur within 14 days after the end of initial treatment.22 Poor medication adherence, antimicrobial resistance, NSAID use, and cigarette smoking are associated with treatment failure.22 Antibiotics that were not used initially for H pylori should be used as therapy for treatment failures.

After several courses of failed H pylori eradication therapy, an ulcer is considered to be refractory to therapy.22 An upper endoscopy is recommended to confirm a nonhealing ulcer, exclude malignancy, and assess H pylori status in patients refractory to therapy. In patients in whom H pylori infection persists and eradication is deemed appropriate, obtaining a culture and determining the sensitivity of H pylori should be considered. Levofloxacin or rifabutin—an antituberculosis agent—may be combined with a PPI and amoxicillin for the treatment of H pylori in patients who have experienced treatment failure.8 Studies of rifabutin-based treatment have achieved an eradication rate of 79% for third-line therapy.27 However, rifabutin is associated with resistance to Mycobacterium tuberculosis.8 Furazolidone, a nitrofuran derivative, has antibacterial efficacy against gram-negative bacteria. Combined with amoxicillin or levofloxacin and a PPI, furazolidone-based treatment in third- or subsequent-line eradication therapy results in eradication rates of 57% to 65%; however, the drug is no longer available in the U.S. because of its side-effect profile.11,27

Guidelines

Two primary treatment guidelines are used in the U.S.: the Maastricht Consensus Report (MCR) and the American College of Gastroenterology Clinical Guideline (ACGCG) on H pylori infection. The MCR recommends triple therapy with a PPI, clarithromycin, and amoxicillin or metronidazole for 14 days. If clarithromycin resistance is less than 15% to 20%, triple therapy is recommended as initial treatment. In susceptible strains, the combination of a PPI, clarithromycin, and metronidazole had an eradication rate of 97%, compared with 88% for the combination of a PPI, clarithromycin, and amoxicillin. Eradication rates for clarithromycinresistant H pylori dropped to 50% and 18%, respectively. Eradication rates were 72% and 97%, respectively, in the case of metronidazole-resistant H pylori. Bismuthcontaining quadruple therapy is an alternative for initial therapy; if not used as initial therapy, it is the preferred second-line treatment. Quadruple therapy achieved an eradication rate of 64%. Levofloxacin and rifamycin are listed as third-line treatments, and susceptibility testing is encouraged.24

The ACGCG recommends triple therapy with a PPI, clarithromycin, and amoxicillin or metronidazole for 14 days. Triple therapy for 14 days’ duration has a confirmed superiority over a 7-day treatment duration. Quadruple therapy with a PPI or H2RA, bismuth, metronidazole, and tetracycline for 10 to 14 days is favored in patients previously treated with a macrolide antibiotic or in those with a true penicillin allergy.10 In quadruple therapy, PPIs have greater efficacy compared with H2RAs in patients with metronidazole-resistant H pylori strains. Sequential therapy requires validation in the U.S. before the ACGCG will recommend it as initial therapy. Treatment for patients with persistent H pylori infection includes quadruple therapy for 7 to 14 days or levofloxacin triple therapy for 10 days; however, the latter also requires validation in the U.S.10

Treatment Side Effects

H pylori eradication therapy is associated with a statistically significantly higher number of adverse events compared with antisecretory, placebo, or no treatment, according to a Cochrane Review.23 Twenty-two percent of patients in the H pylori–eradication group experienced side effects, versus 8% of the comparison group. Nausea, vomiting, abdominal pain, headache, and diarrhea are common side effects associated with treatment of H pylori. Taste disturbances may occur with metronidazole and clarithromycin. Because metronidazole can create a disulfiram-like reaction when it is combined with alcohol, patients should be advised to avoid alcohol. Tetracycline is associated with photosensitivity and may cause tooth discoloration in children. Bismuth is associated with darkening of the stool and of the tongue. Levofloxacin carries a warning of an increased risk of tendinitis, which may not always resolve upon discontinuation of the drug.27 Vaginal candidiasis may result during or after treatment.

While PPIs may alter the bioavailability of orally administered medications because of an increase in intragastric pH and some PPIs inhibit the hepatic CYP2C19 pathway, an FDA database review found limited drug interactions with PPIs. However, the FDA recommends that coadministration of clopidogrel with omeprazole or esomeprazole be avoided, as the combination may reduce the effectiveness of clopidogrel.22

Probiotics

Probiotics are live microbial organisms that may partially restore microecology in the intestine. Probiotics have been shown to reduce the risk of adverse effects associated with H pylori treatment.33 In addition, increased rates of eradication have been reported.27 The effect of probiotics on eradication rates and adverse events was examined in a meta-analysis by Tong and colleagues.33 The eradication rate for triple therapy plus probiotics was 83.6%, compared with 74.8% for triple therapy without probiotics. In the same metaanalysis, probiotics had a positive impact on diarrhea and taste disturbances.33

Adherence

Multiple medications, increased administration frequency, adverse effects, and cost all negatively affect adherence.22 Poor adherence is associated with antibiotic resistance and lower levels of eradication; therefore, it is essential to stress the importance of completing the treatment exactly as prescribed.27 Documentation of patient instructions can play an important role in improving adherence.

ROLE OF THE PHARMACIST

Efficacy, antibiotic resistance, cost, side-effect profile, allergies, and ease of administration should be taken into account when an individualized treatment regimen is being selected for a patient with H pylori. Bismuth-based quadruple therapy may be the treatment of choice when cost is the most important factor; however, it is the most extensive regimen.22 Patients with PUD should eliminate or reduce stress, cigarette smoking, alcohol, NSAIDs, and additional medications associated with dyspepsia, as well as avoid foods and beverages that contribute to dyspepsia or ulcer symptoms. The pharmacist should assess patient use of alcohol and oral contraceptives and counsel appropriately. Antibiotics may decrease the effectiveness of oral contraceptives. Allergies and the type of reaction to penicillin should also be verified. An explanation of why antibiotic and antiulcer combinations are used, when and how to take medications, what adverse effects to expect, and the importance of adherence should be provided.

When patients have greater knowledge about their illness and the importance of adherence, improvements are seen in adherence and eradication.27 Patients should contact their health care provider should blood in the stool, vomiting, or abdominal pain occur or if symptoms persist or return after H pylori eradication therapy. The eradication of H pylori offers a definite role for pharmacists.

REFERENCES

  1. Hajdu SI. Nobel laureate pathologists. Ann Clin Lab Sci. 2009;39: 196-198.
  2. Warren JR, Marshall B. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. 1983;321:1273-1275.
  3. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease. Helicobacter pylori in peptic ulcer disease. JAMA.1994;272:65-69.
  4. Yamaoka Y. Mechanisms of disease: Helicobacter pylori virulence factors. Nat Rev Gastroenterol Hepatol. 2010;7:629-641.
  5. Malaty HM. Epidemiology of Helicobacter pylori infection. Best Pract Res Clin Gastroenterol. 2007;21:205-214.
  6. Elitsur Y, Dementieva Y, Rewalt M, Lawrence Z. Helicobacter pylori infection rate decreases in symptomatic children: a retrospective analysis of 13 years (1993-2005) from a gastroenterology clinic in West Virginia. J Clin Gastroenterol. 2009;43:147-151.
  7. Nakajima S, Nishiyama Y, Yamaoka M, et al. Changes in the prevalence of Helicobacter pylori infection and gastrointestinal diseases in the past 17 years. J Gastroenterol Hepatol. 2010;25:S99-S110.
  8. McColl KE. Helicobacter pylori infection. N Engl J Med. 2010;362:1597-1604.
  9. Ford AC, Axon AT. Epidemiology of Helicobacter pylori infection and public health implications. Helicobacter. 2010;15(suppl 1):1-6.
  10. Chey WD, Wong BC, Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102:1808-1825.
  11. World Gastroenterology Organisation. World Gastroenterology Organisation Global Guideline: Helicobacter pylori in developing countries. J Clin Gastroenterol. 2011;45:383-388.
  12. Mourad-Baars P, Hussey S, Jones NL. Helicobacter pylori infection and childhood. Helicobacter. 2010;15(suppl 1):53-59.
  13. Tummala S, Keates S, Kelly CP. Update on the immunologic basis of Helicobacter pylori gastritis. Curr Opin Gastroenterol. 2004;20:592-597.
  14. Basso D, Plebani M, Kusters JG. Pathogenesis of Helicobacter pylori infection. Helicobacter. 2010;15(suppl 1):14-20.
  15. Kuwahara H, Miyamoto Y, Akaike T, et al. Helicobacter pylori urease suppresses bactericidal activity of peroxynitrite via carbon dioxide production. Infect Immun. 2000;68:4378-4383.
  16. Malfertheiner P, Chan FK, McColl KE. Peptic ulcer disease. Lancet. 2009;374:1449-1461.
  17. Tan VP, Wong BC. Helicobacter pylori and gastritis: untangling a complex relationship 27 years on. J Gastroenterol Hepatol. 2011;26(suppl 1): 42-45.
  18. CDC. Helicobacter pylori: fact sheet for health care providers. www.cdc.gov/ulcer/files/hpfacts.pdf. Accessed August 28, 2011.
  19. de Vries AC, Kuipers EJ. Helicobacter pylori infection and nonmalignant diseases. Helicobacter. 2010;15(suppl 1):29-33.
  20. Konturek PC, Konturek SJ, Brzozowski T. Helicobacter pylori infection in gastric cancerogenesis. J Physiol Pharmacol. 2009;60:3-21.
  21. Calvet X, Lehours P, Lario S, Megraud F. Diagnosis of Helicobacter pylori infection. Helicobacter. 2010;15(suppl 1):7-13.
  22. Berardi RR, Fugit RV. Peptic ulcer disease. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: McGraw-Hill Medical; 2011.
  23. Ford AC, Delaney BC, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori positive patients. Cochrane Database Syst Rev. 2006;(2):CD003840.
  24. Malfertheiner P, Megraud F, O’Morain C, et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut. 2007;56:772-781.
  25. Furuta T, Graham DY. Pharmacologic aspects of eradication therapy for Helicobacter pylori infection. Gastroenterol Clin North Am. 2010;39:465-480.
  26. Gisbert JP, Calvet X, O’Connor A, et al. Sequential therapy for Heli cobacter pylori eradication: a critical review. J Clin Gastroenterol.2010;44:313-325.
  27. O’Connor A, Gisbert JP, McNamara D, O’Morain C. Treatment of Helicobacter pylori infection 2010. Helicobacter. 2010;15(suppl 1):46-52.
  28. Malfertheiner P, Bazzoli F, Delchier JC, et al. Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial. Lancet. 2011;377:905-913.
  29. Jafri NS, Hornung CA, Howden CW. Meta-analysis: sequential therapy appears superior to standard therapy for Helicobacter pylori infection in patients naive to treatment. Ann Intern Med. 2008;148:923-931.
  30. Gisbert JP, Pajares JM. Treatment of Helicobacter pylori infection: the past and the future. Eur J Intern Med. 2010;21:357-359.
  31. Greenberg ER, Anderson GL, Morgan DR, et al. 14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: a randomised trial. Lancet. 2011;378: 507-514.
  32. Gisbert JP, Khorrami S, Carballo F, et al. H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. Cochrane Database Syst Rev. 2004;(2):CD004062.
  33. Tong JL, Ran ZH, Shen J, et al. Meta-analysis: the effect of supplementation with probiotics on eradication rates and adverse events during Helicobacter pylori eradication therapy. Aliment Pharmacol Ther.2007;25:155-168.

Back to Top


  Take Test  |  View Questions