Helicobacter pylori (H. pylori) is strongly associated with a variety of upper gastrointestinal diseases, as well as with extra-gastric diseases such as refractory iron deficiency anemia and immune thrombocytopenic purpura, and the problem of decreasing H. pylori eradication rates has become increasingly acute over time, with some patients failing eradication therapy even when given remedial treatment. The reasons for the failure of H.pylori eradication therapy are multiple, including the factors of the H.pylori strain itself, host factors, environmental factors, different clinical diseases and treatment methods. I. Bacterial factors 1. H. pylori resistance to antibiotics is the most important reason for eradication failure: H. pylori can be resistant to a variety of antibiotics through mutations in its own chromosomes, especially the widespread prevalence of H. pylori resistance to metronidazole and clarithromycin, which is an important factor leading to H. pylori eradication treatment failure. The results of our study of 10 consecutive years of monitoring H. pylori resistance to antibiotics in Beijing showed that the rate of H. pylori resistance to clarithromycin, metronidazole and levofloxacin was on the rise from 1999 to 2009. However, even when treated with antibiotics that are sensitive to all of H. pylori, some patients still fail treatment. About 50% of patients who fail H. pylori eradication therapy cannot be explained by H. pylori resistance, but are related to other causes. 2. Impact of H. pylori virulence factors on eradication therapy: The main virulence factors of H. pylori include vacuolar cytotoxin (VacA) and cytotoxin-associated protein (CagA), which play an important role in the pathogenesis of H. pylori and are closely related to the severity of clinical disease, and their impact on eradication therapy. The results of a study showed that CagA-negative strains are a risk factor for treatment failure, which may be related to the lower replication rate of strains than positive strains, which leads to their reduced susceptibility to antibiotics. 3, H. pylori colonization site on the eradication of treatment: the results of an animal study showed that the presence of H. pylori in the junction of the gastric sinus and gastric body may escape the action of antibiotics, which may be due to the junction of the tissue structure is different from the gastric sinus or gastric body, so that the biological behavior of H. pylori colonized in this area is also different from the sinus or gastric body of H. pylori. pylori in the junctional area may have a different biological behavior from that of H. pylori in the sinus or gastric body, which makes it insensitive to antibiotics and leads to treatment failure. It was also found that the number of H. pylori colonized in the gastric sinus decreased significantly when treated with acid inhibitors alone, while the number of H. pylori in the gastric body increased significantly, a phenomenon that may be related to the reduced efficacy of eradication therapy after pre-treatment with proton pump inhibitors (PPIs). . The effect of bacterial load on eradication therapy: When the bacterial load in the stomach is too high, it will easily lead to treatment failure of patients. The DOB value of 13C breath test can semi-quantitatively respond to the level of bacterial load, and when its detection value is 10 times higher than the upper limit of normal value, it suggests that the bacterial load may be too high. Second, host factors 1, the impact of intragastric pH on H. pylori eradication therapy: the pH of intragastric acidity can range from 2 to 7.2, while H. pylori can still survive and proliferate at pH 4-5 in the stomach. Most antibiotics have no significant activity against H. pylori in a low acid environment, such as amoxicillin and clarithromycin, and their minimum inhibitory concentration (MIC) against H. pylori is dependent on intragastric pH, which increases when the pH decreases, and general in vitro tests require a pH of 7.0 when determining the MIC of antibiotics. Therefore, PPI must be added to the regimen for the treatment of H. pylori infection in order to increase the pH in the stomach and thus improve the antibacterial activity of the antibiotic against H. pylori. The effect of host genotype on H. pylori eradication therapy: cytochrome P450 (CYP) 2C19 gene polymorphism affects the efficacy of PPI-containing eradication regimens, as PPI is metabolized mainly through the CYP2C19 pathway. mt), in addition to Hp resistance to antibiotics, the strong metabolic type of CYP2C19 is also an important reason for the failure of H. pylori eradication therapy. 3. Poor patient compliance is one of the main reasons for H. pylori eradication failure: In addition to bacterial resistance to antibiotics affecting patient outcomes when treated with the standard regimen recommended by consensus, poor patient compliance is also a common reason for treatment failure. One study showed that 10% of patients with poor adherence took less than 85% of the overall dose, leading to a lower eradication rate. Poor adherence not only leads to treatment failure, but also leads to drug resistance in H. pylori due to irregular dosing, making subsequent treatment more difficult. 4, host immune status on H.pylori eradication therapy: the body immune status on H.pylori eradication therapy also has a certain impact. One study showed that serum interleukin-4 (IL-4) levels were significantly lower in patients who failed H.pylori eradication therapy compared to those who successfully eradicated H.pylori or those with untreated H.pylori infection. Administration of a therapeutic H.pylori vaccine orally to mice chronically infected with H.pylori resulted in successful eradication of H.pylori through TH2 activation-mediated immune responses in the gastrointestinal mucosa. 5. Impact of gender and age on Hp eradication therapy: A US meta-study analyzed 3624 patients and found that female patients had significantly higher resistance rates to metronidazole and clarithromycin than males, leading to treatment failure. Older patients also contribute to eradication treatment failure because they are more likely to develop resistance to clarithromycin. In a Japanese study, the eradication success rate was higher in patients older than 50 years of age than in patients younger than 50 years of age when first-line therapy with lansoprazole combined with amoxicillin and clarithromycin was used, and the reason for this may be related to the high incidence of atrophic gastritis in older patients resulting in reduced gastric acid secretion. 6, the impact of smoking on H.pylori eradication treatment: most studies have shown that smoking reduces the eradication rate of H.pylori, and some studies suggest that the eradication rate of H.pylori in patients with duodenal ulcer (DU) who smoke is significantly lower than that of nonsmoking patients. The impact of different clinical conditions on H.pylori eradication treatment The eradication rate of H.pylori is generally higher in patients with DU than in patients with non-ulcer dyspepsia (NUD). In a French meta-analysis study of 2751 patients, 25.8% of whom failed eradication, the H.pylori eradication failure rate in DU patients was 21.9% significantly lower than that in NUD patients, 33.7% (P < 10-6), and drug sensitivity tests suggested that the resistance rate to clarithromycin was significantly lower in DU patients than in NUD patients, which may This may be the main reason for the lower eradication rate of H. pylori in NUD patients. In addition, if patients present with coexisting sinusitis and gastritis, their H.pylori infection is easily eradicated. A meta-analysis that included 966 patients from 8 studies showed that diabetes is a risk factor for failure of H.pylori eradication, and for diabetic patients, a longer course of treatment may be needed in the treatment of H.pylori infection and new treatment regimens have yet to be developed. Environmental factors It is generally recommended that patients be examined at least 4 weeks after the completion of H.pylori eradication therapy to determine whether their H.pylori has been eradicated, but there is a risk that patients may have relapsed or become reinfected while they are waiting to be reexamined. This suggests that the important transmission route of H.pylori is person-to-person transmission, and that factors such as poor economic status and hygiene, low literacy, crowded housing, and non-tap water sources are all high-risk factors for H.pylori infection or reinfection. Fifth, the impact of the treatment plan 1, the choice of antibiotics on the eradication of H. pylori treatment: the choice of initial treatment or repeated selection of antibiotics that have become resistant to H. pylori when retreatment is one of the important reasons for treatment failure, such as repeated selection of antibiotics prone to secondary resistance in remedial treatment (such as clarithromycin, metronidazole and levofloxacin) is an important cause of remedial The choice of antibiotics prone to secondary resistance (e.g., clarithromycin, metronidazole, and levofloxacin) in remedial therapy is an important cause of treatment failure. The combination of PPI, bismuth preparation and antibiotics can not only reduce the production of resistant strains of H.pylori, but also increase the activity of antibiotics and the concentration of antibiotics in the stomach, thus improving the efficacy of eradication of H.pylori. 2, the impact of the course of treatment on the eradication of H. pylori: in the selection of standard H. pylori eradication treatment regimen, insufficient course of treatment is also a cause of treatment failure. An adequate or appropriately prolonged course of treatment not only improves the eradication rate of H. pylori but also reduces the development of antibiotic resistance to H. pylori. Early international consensus has recommended that either first-line or second-line treatment regimens should not be less than 7 days, and with the change of time, new consensus at home and abroad suggests that in areas with severe bacterial resistance can be improved by extending the course of treatment to 10-14 days. 3, the impact of adverse drug reactions on eradication therapy: due to adverse drug reactions, such as patients are allergic to drugs or can not tolerate, so that patients are forced to stop the drug, can not complete the treatment, is also one of the important reasons for the failure of H. pylori eradication therapy. Sixth, how to improve the eradication rate of H. pylori Individualized and rational selection of treatment options: in the selection of treatment options, pay attention to the patient's previous history of antibiotic application, to avoid repeated selection of antibiotics that can easily lead to secondary resistance; for 2 times by the regular program of treatment failure, the patient needs to be re-evaluated, for patients who need to receive treatment, drug sensitivity testing can be considered to select sensitive antibiotic therapy. Improve patient compliance: when selecting treatment regimens, attention should be paid to the patient's age, history of comorbid diseases, history of drug use, history of drug allergy, etc., attention should be paid to avoid drug interactions, individualized selection of reasonable treatment regimens to reduce adverse reactions; prior to treatment, adequate communication with the patient, informing him/her of the detailed method of taking the drug and its possible adverse reactions in treatment, can improve patient compliance and reduce the risk of treatment failure. Adjuvant therapy: With the growing problem of antibiotic resistance in H. pylori, non-antibiotic adjuvant therapies are beginning to receive attention from researchers. Adding probiotics to the regimen can reduce the incidence of adverse effects, especially diarrhea, and thus improve patient compliance with treatment. The inclusion of herbal medicines in treatment regimens has also been one of the hot topics of research in recent years. The development of antibacterial phytopharmaceuticals has been a hot research topic in recent years. A variety of phytoconstituents have been found to have antibacterial activity against H. pylori, and their combination with antibiotics has reduced bacterial resistance to antibiotics and synergistic antibacterial effects. The search for new non-antibiotic drugs and the development of vaccines to improve the efficacy of H. pylori eradication, reduce the pathogenicity of H. pylori or reduce the adverse effects in treatment is a trend of future research.