Treatment of Helicobacter pylori infection: Current and future insights

Helicobacter pylori (H. pylori) is an important major cause of peptic ulcer disease and gastric malignancies such as mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma worldwide. H. pylori treatment still remains a challenge, since many determinants for successful therapy are involved such as individual primary or secondary antibiotics resistance, mucosal drug concentration, patient compliance, side-effect profile and cost. While no new drug has been developed, current therapy still relies on different mixture of known antibiotics and anti-secretory agents. A standard triple therapy consisting of two antibiotics and a proton-pump inhibitor proposed as the first-line regimen. Bismuth-containing quadruple treatment, sequential treatment or a non-bismuth quadruple treatment (concomitant) are also an alternative therapy. Levofloxacin containing triple treatment are recommended as rescue treatment for infection of H. pylori after defeat of first-line therapy. The rapid acquisition of antibiotic resistance reduces the effectiveness of any regimens involving these remedies. Therefore, adding probiotic to the medications, developing anti-H. pylori photodynamic or phytomedicine therapy, and achieving a successful H. pylori vaccine may have the promising to present synergistic or additive consequence against H. pylori, because each of them exert different effects.     

Treatment of Helicobacter pylori infection: A clinical practice update

Background

Helicobacter pylori infection is still frequent in the community and all infected subjects should be offered an eradication therapy. Nowadays physicians have to face the challenge of antibiotic resistance in treating Helicobacter pylori‐infected individuals.

Aim

This review provides an overview of current international guidelines and reports recent evidence from systematic reviews and clinical trials on the treatment of Helicobacter pylori infection and should help physicians to better treat their patients.

Results

General rules to optimize the management of Helicobacter pylori infection include: (i) considering previous patient's exposure to antibiotics; (ii) using high dose of proton‐pump inhibitors; and (iii) avoiding repeating the same regimen, if it has already failure. Bismuth quadruple therapy and concomitant therapy are the best first‐line empirical treatments in areas with high clarithromycin resistance and in individuals with previous use of macrolides; otherwise, the 14‐day clarithromycin‐containing triple therapy is a valid regimen. The sequential therapy is no longer a suggested treatment by international guidelines.

Conclusions

Current international guidelines are consistent in defining treatment strategies for Helicobacter pylori infection. The use of national registries to monitor the efficacy and tolerability of different regimens in the real world of clinical practice is now needed.     

Management of Helicobacter pylori infection

Helicobacter pylori is the cause of peptic ulcer, gastric cancer and gastric lymphoma. Diagnosis of H. pylori infection can be made using invasive and noninvasive tests. Invasive tests based on endoscopy, such as histology, are recommended when a gastric malignancy is suspected. Alternatively, noninvasive tests, such as the urea breath test and stool tests are useful for H. pylori diagnosis and follow-up. Triple therapy with either amoxicillin or metronidazole, clarithromycin and proton pump inhibitor given twice daily for 7–14 days is the recommended first-line treatment, after having checked the individual clarithromycin antimicrobial susceptibility. A triple therapy with levofloxacin, amoxicillin and proton pump inhibitor for 10–14 days should be used as second-line treatment, where the strains are susceptible to fluoroquinolone. Alternatively, bismuth-based quadruple therapy is recommended.     

Management of Helicobacter pylori infection

Helicobacter pylori is the cause of most peptic ulcer disease and a primary risk factor for gastric cancer. Eradication of the organism results in ulcer healing and reduces the risk of ulcer recurrence and complications. Testing and treatment have no clear value in patients with documented nonulcer dyspepsia; however, a test-and-treat strategy is recommended but for patients with undifferentiated dyspepsia who have not undergone endoscopy. In the office setting, initial serology testing is practical and affordable, with endoscopy reserved for use in patients with alarm symptoms for ulcer complications or cancer, or those who do not respond to treatment. Treatment involves 10- to 14-day multidrug regimens including antibiotics and acid suppressants, combined with education about avoidance of other ulcer-causing factors and the need for close follow-up. Follow-up testing (i.e., urea breath or stool antigen test) is recommended for patients who do not respond to therapy or those with a history of ulcer complications or cancer.     

Diagnosis of Helicobacter pylori infection

Peptic ulcer in elderly patients may be associated with Helicobacter pylori infection. Diagnosis for H. pylori infection should be needed in these patients. The test may be resulted in false negative in case of invasive diagnostic methods based gastric biopsy, because atrophic gastritis and intestinal metaplasia developed in patients may not be able to detect scarce infection of the bacterium. Urea breath test or stool antigen test are recommended for diagnosis of H. pylori infection in patients. It is suitable for patients, because of the non invasive nature of these diagnostic tests.     

Treatment strategies and preventive methods for drug-resistant Helicobacter pylori infection

The infection and drug resistance rates of Helicobacter pylori (H. pylori) are high and must be prevented and treated by better strategies. Based on recent research advances in this field as well as the results from our team and those on traditional Chinese medicine, we review the causes of drug resistance, and prevention and treatment strategies for drug-resistant H. pylori infection, with an aim to make suggestions for the development of new drugs, such as establishment of new target identification and screening systems, modification of existing drug structures, use of new technologies, application of natural products, and using a commercial compound library. This article may provide reference for eradication of drug-resistant H. pylori.     

Helicobacter pylori infection and eradication

H. pylori infection is associated with various gastroduodenal diseases such as gastritis, peptic ulcer, gastric cancer, gastric MALT lymphoma. H. pylori infection is suggested that it plays a role as protective factor not promoting factor for reflux esophagitis and GERD. Epidemiological studies showed lower prevalence of H. pylori infection in reflux esophagitis and Barrett's esophagus comparing the control. Increased occurrence of reflux esophagitis after curing of H. pylori infection was reported. However, the relationship between H. pylori infection and reflux esophagitis has not been actually made clear. Also the mechanism of reflux esophagitis occurrence after H. pylori eradication is not obscure.     

Helicobacter pylori infection in Finland

Helicobacter pylori causes chronic gastritis worldwide and it is the most important single factor in peptic ulcer disease. Up to half of H. pylori infected individuals develop atrophic gastritis over years and decades. H. pylori infection has also been classified as a class I carcinogen in human gastric cancer. Most infections are obtained in childhood, in Finland mainly before the age of 7 years but the exact transmission routes are not known. The infection shows an age-dependent pattern, the infection being rare among children but gradually becoming more prevalent among older age groups. As new infections are few in adults and the infection only rarely disappears without effective anti-microbial therapy, the occurrence of the infection in the old actually reflects the prevalence of the infection in their childhood. In developed countries, such as Finland, a rapid decline of H. pylori prevalence rate has been demonstrated. In order to speed up this natural decline of the infection, a unique population based 'screen and treat' project was started in Vammala, a semiurban south-western community in Finland. In this survey, young inhabitants were offered diagnosis and treatment for H. pylori.     

Helicobacter pylori infection and GERD

Helicobacter pylori (H. pylori) is an important pathogen that is known to be associated with gastritis, peptic ulcer diseases, and gastric cancer. The association between H. pylori infection and gastro-esophageal reflux disease (GERD) is, however, uncertain. Recent studies indicate that the prevalence of H. pylori is significantly lower in patient with GERD from East Asia than in patients from Western Europe and North America, and that H. pylori might protect against GERD. The frequency of hypochlorhydria might due to atrophic gastritis induced by H. pylori infection is associated with the low prevalence of GERD in Japan.     

Helicobacter pylori infection in Finland

Helicobacter pylori causes chronic gastritis worldwide and it is the most important single factor in peptic ulcer disease. Up to half of H. pylori infected individuals develop atrophic gastritis over years and decades. H. pylori infection has also been classified as a class I carcinogen in human gastric cancer. Most infections are obtained in childhood, in Finland mainly before the age of 7 years but the exact transmission routes are not known. The infection shows an age‐dependent pattern, the infection being rare among children but gradually becoming more prevalent among older age groups. As new infections are few in adults and the infection only rarely disappears without effective antimicrobial therapy, the occurrence of the infection in the old actually reflects the prevalence of the infection in their childhood. In developed countries, such as Finland, a rapid decline of H. pylori prevalence rate has been demonstrated. In order to speed up this natural decline of the infection, a unique population based ‘screen and treat’ project was started in Vammala, a semiurban south‐western community in Finland. In this survey, young inhabitants were offered diagnosis and treatment for H. pylori.     

Helicobacter pylori infection and migraine

The study is aimed to ascertain whether the Helicobacter pylori (Hp) infection is responsible for the vulnerability to oxidative stress observed in migraineurs. Hp serological positivity was assessed by ELISA evaluation of specific IgA and IgG antibodies in 30 subjects (11 males and 19 females) suffering from migraine without aura during the headache-free period. The Hp infection was detected in 16.7% of migraineurs. Plasma accumulation of peroxidative substances (TBA-RS), an index of systemic oxidative status, was increased in migraineurs without Hp infection with respect to controls (P< 0.001), while no significant differences of TBA-RS were found in migraineurs with or without Hp infection. Unmodified values of plasma nitrite/nitrate concentrations, expression of systemic nitric oxide (NO), were obtained in migraineurs in comparison to controls indicating that Hp infection does not modify the plasma oxidative status and the systemic NO bioavailability of migraineurs. In conclusion, our results do not support any specific correlation between Hp infection and migraine.     

Treatment of Helicobacter pylori infections

The available literature on the relationship between severaldiseases and Helicobacter pylori (H. pylori) is reviewed. Duodenalulcer, gastric ulcer, complicated peptic ulcer, abdominal symptomsand gastroduodenal mucosal damage during the use of non-steroidalanti-inflammatory drugs (NSAIDs), non-ulcer dyspepsia (NUD)and gastric malignancy are discussed. The case for and againsteradication is critically discussed. Eradication of H. pylorishould be pursued in all patients with peptic ulcer disease,whether they are using NSAIDs or not. Eradication of H. pyloriin the treatment of NUD should be considered experimental. Treatmentaimed at the eradication of H. pylori should be considered inall patients with low-grade malignant mucosaassociated lymphoidtissue (MALT) lymphoma and in all patients with Menetrier'sdisease. Finally, this treatment should be considered in a subsetof H. pylori-infected patients who possibly are at an increasedrisk of gastric cancer: patients with a strong family historyof gastric carcinoma and patients in need of long-term treatmentwith a proton-pump inhibitor. In view of the importance of patientcompliance, the risk of side-effects and the possibility ofinducing metronidazole resistance when treatment with a metronidazole-containingregimen is used, treatment aimed at the eradication of H. pylorishould be carefully implemented and monitored.     

Serological diagnosis of Helicobacter pylori infection

H. pylori gastritis elicits both a local and a systemic immune response. Although multiple invasive tests are available for the diagnosis of H. pylori infection, serum testing for anti-H. pylori antibodies is a minimally invasive test available to diagnose this infection. Latex agglutination is available, but most kits use ELISA. The sensitivities and specificities of many commercial kits were more than 90%. However, most of these serologic detection kits were made in Western countries. There might been the influence of geographical differences on test results. Recently, serological test has been reported about of usefulness in monitoring after eradication therapy at long-term period.