Recently studies showed that the eradication rate of H. pylori fail to exceed 80% and even falls into an unacceptable range. A major cause of treatment failure is associated with antibiotic resistance and poor patient compliance. However, the refractory infection of H. pylori is still existing, although patients have good compliance and receive standardized treatment. This phenomenon is likely attributed to the different ratio of sensitive and resistance in H. pylori, the difference of Amoxicillin resistance between in vivo and in vitro, the difference between phenotype and genotype or the influence of micro-environment in the stomach. In order to solve the refractory infection of H. pylori, investigators performed a muti-center study together with other 14 institutions. In this study, investigators will select the patients with refractory infection of H. pylori after two standardized treatment from patients with first eradication therapy of H. pylori infection. Then, investigators will perform a high-throughput sequencing for patients in groups. Finally, investigators will compare the differences between the patients with first successful eradication and patients with refractory infection of H. pylori, such as drug resistance gene mutation, phenotype and genotype, the mechanisms of Amoxicillin resistance and micro-environment in stomach.

Inclusion Criteria:

1. Age 18~70 years old, male or female, the first eradication therapy of H. pylori infection patients.
2. Symptoms of abdominal pain, bloating, acid efflux, belching, nausea, vomiting, heartburn, chest pain, vomiting, melena, etc.
3. Unused antibiotics, bismuth, H2 receptor antagonists or PPIs by nearly 4 weeks
4. 13C-labelled urea breath test positive.
5. Agreed to Helicobacter pylori culture and sensitivity testing taken by endoscopy gastric biopsy specimens,and the result of culture was positive.
6. Agreed to Helicobacter pylori eradication therapy and cooperate with the eradication efficacy follow-up survey.

Exclusion Criteria:

1. Severe heart, liver, kidney dysfunction.
2. Pregnant or lactating women.
3. Complications of bleeding, perforation, pyloric obstruction, cancer.
4. Esophageal,gastrointestinal surgery history.
5. Patients can not properly express their complaints,such as psychosis, severe neurosis.
6. Taking nonsteroidal antiinflammatory drugs (NSAIDs) or alcohol abusers.
7. Allergic to penicillin or either drugs of the 6 antibiotic tested by susceptibility testing.