H. pylori infection is one of the most common chronic infections, and its associated gastroduodenal diseases such as chronic active gastritis, peptic ulcer, MALT lymphoma, and gastric cancer seriously affect people’s health. as research has intensified, various testing methods have become popular and multiple guidelines have been formed, a unified understanding of H. pylori has been reached and a consensus on its treatment has been formed. October 3, 2005 Barry Marshall and Robin Warren were awarded the 2005 Nobel Prize in Physiology and Medicine. However, the success rate of drug eradication of H. pylori has decreased significantly in recent years, and the problem of drug resistance of H. pylori is becoming more and more prominent. Why is it resistant? How to counteract it after it is resistant? All worth our research. 1, the difficulty of H. pylori eradication is an important reason for the formation of drug resistance H. pylori colonized in the gastric mucus, and can produce “ammonia cloud” self-protection, coupled with the impact of gastric acid in the stomach on the effectiveness of antimicrobial agents and other factors that determine the difficulty of H. pylori eradication, must be combined with drugs, usually proton pump inhibitors or bismuth as The “triple therapy” based on proton pump inhibitors or bismuth can only reach about 80%, and the low eradication rate itself increases the chance of drug resistance. In addition, even with the application of antibiotics that are sensitive to Hp, some patients still fail treatment, and about 50% of eradication cases cannot be explained by Hp resistance to antibiotics. Rather, it may be related to Hp virulence factors and bacterial colonization sites. Vacuole-forming cytotoxin (VacA) and cytotoxin-associated protein (CagA) play an important role in the pathogenesis of Hp and correlate with clinical disease severity, but the exact relationship between them and Hp resistance needs further study. An animal study showed that Hp present at the junction of the gastric sinus and body may escape the action of antibiotics. The reason for this may be that the tissue structure of the sinusoidal junction is different from that of the sinus or gastric body. The biological behavior of Hp colonized in this area is also different from that of those colonized in the sinus or gastric body, which makes them insensitive to antibiotics and leads to failure of eradication therapy. 2, H. pylori resistance to increase the human factor (1) the abuse of antimicrobial agents is an important reason for drug resistance. The H p resistance to metronidazole is global, it is reported that the H p resistance rate to metronidazole in developing countries is 50%-80%. It is significantly higher than the 9%-12% in developed countries; the resistance rate of clarithromycin is also increasing. Amoxicillin and tetracycline resistance is relatively rare. In Beijing, the resistance of H p to antibiotics was 36.3% for metronidazole and 14.5% for clarithromycin in 1999, and rose to 43.1% for metronidazole and 18.3% for clarithromycin in 2000-2001. In Shanghai, China, the rate of H p resistance is also increasing from 1995 to 1999, the rate of metronidazole resistance increased from 42% to 70%, and the rate of clarithromycin increased from 0 to 10%. The eradication rates of H p strains sensitive to both metronidazole and clarithromycin were 91, 7% and 80% for the one-week triple and 3-day quadruple regimens, respectively, while the eradication rates of metronidazole-resistant strains were only 57.1% and 33.3%, respectively (2) The popularity of methods to detect H. pylori is one of the reasons for the increase in drug resistance. Because of the widespread use of various H. pylori detection methods, especially non-invasive detection methods, more easily accepted by the general public, some units even H. pylori detection as a routine physical examination program, the results of H. pylori-positive patients, including some normal people, including many of those who do not need to eradicate the random treatment, increasing the chance of drug-resistant strains. Although screening and eradication of H. pylori, so-called “test-and-treat”, has been proposed in areas with a high incidence of gastric cancer in order to reduce the incidence of gastric cancer, it should not be advocated in the general population. (3) The arbitrary nature of treatment increases the development of secondary drug resistance. Many consensus and guidelines have been developed for the treatment of H. pylori, which further clarify the indications and protocols for treatment, such as peptic ulcer, MALT lymphoma, postoperative gastric cancer, and family history of gastric cancer are highly recommended for eradication, but general gastritis and functional dyspepsia do not support eradication. The polymorphism of H. pylori genome structure determines the difference of pathogenicity and virulence (10), which provides a theoretical basis for us to differentiate H. pylori infection in different diseases. The triple therapy based on proton pump inhibitor and bismuth plus two antimicrobials has been advocated in the treatment protocol (2). However, the fact that some doctors, especially non-specialists, are still confused and very arbitrary in whether they should treat and what regimen to choose, such as using a single antimicrobial agent or using the same regimen repeatedly and unchangingly, undoubtedly increases the occurrence of secondary drug resistance. (4) Host factors: host factors mainly include host genotype, intragastric pH, patient compliance, host immune status, gender, age, smoking and mixed infection with different Hp strains, and poor patient compliance not only lead to failure of eradication therapy, but also Hp resistance due to irregular dosing. A US meta-study analyzing 3624 patients found that female patients had significantly higher rates of resistance to metronidazole and clarithromycin than males, and older patients were more likely to develop resistance to clarithromycin. In mixed infections with different genotypic Hp strains. Bacterial resistance to antibiotics is of particular clinical importance. Mixed infections of different MIC strains can exist in the same patient, and mixed infections of metronidazole-resistant strains are common. It is suggested that the drug resistance of Hp may have some correlation with some specific strains of infection or mixed infection. 3, H. pylori drug-resistant countermeasures (1) remedial therapy. H. pylori eradication failure should be adjusted after the program. Recent studies have confirmed that metronidazole and clarithromycin resistance has increased significantly, while amoxicillin is relatively small, so in the initial treatment cases, as long as the penicillin is not allergic, should try to use the program containing amoxicillin. And in cases of treatment failure, which we might call retreatment cases, we can take remedial treatment. ①Adjust the dose and course of the original regimen. If the antimicrobial dose is insufficient, the dose should be increased; or the one-week course of treatment should be extended to two weeks. ② Adopt a new regimen. If the antimicrobial agent in the original regimen is replaced, choose an antimicrobial agent not used in the original regimen among the commonly used metronidazole, clarithromycin, amoxicillin, and furazolidone instead. Recently, it has been found that levofloxacin has better anti-H. pylori effect, and we have used esomeprazole 40mg,qd, amoxicillin 1, 0, bid, and levofloxacin 0, 2, bid as remedial regimen in clinical practice with better efficacy. In addition, some studies have shown that bismuth is rarely resistant to H. pylori, so adding bismuth to the original triple therapy can reduce the occurrence of drug resistance; and continuing the use of bismuth for 4-6 weeks after the course of treatment can also improve the success rate of eradication.3 Those who have the conditions can conduct drug sensitivity tests to select the use of sensitive antimicrobial agents. Due to the high condition of H. pylori culture, it is often difficult to be widely used in clinical practice. Also look for new antibiotics that are less likely to develop resistance. Aminoacetic acid is a simple amino acid. It is a metabolite of some bacteria. Excess of aminoacetic acid can inhibit bacterial growth. Therefore it is used as a low toxicity non-specific antibacterial agent in animals. In vitro studies have shown that aminoacetic acid has a significant inhibitory effect on Hp, as well as on clarithromycin-resistant strains, so it is expected to be a new Hp drug. The broad-spectrum antibiotic rifaximin can be concentrated in the gastrointestinal tract, and in vitro experiments have shown that it has high anti-Hp activity. It is also expected to be a new anti-Hp drug but whether these drugs can be used for Hp eradication therapy is yet to be confirmed by further studies. (2) Learn to give up. H. pylori eradication failure is not lacking in general gastritis, functional dyspepsia, etc. does not support eradication, in some of these cases even repeated use of many programs have failed, some patients even produce depression, anxiety, why we can not tell the patient can be put on hold? The harm of H. pylori should not be exaggerated, not to mention that H. pylori is the main but not the only causative factor of peptic ulcer and other diseases, and the relationship between H. pylori as a carcinogen and gastric cancer is still to be studied in depth. For those who fail in consecutive treatments, it is recommended to perform eradication treatment at an interval of 3-6 months. Because repeated treatment will cause Hp to spherical change and thus become more and more insensitive to antibiotics. (3) Combination of Chinese and Western medicine. Chinese medical theory has confirmed (14) that H. pylori is a “damp-heat poisonous evil”, wet and sticky, which determines the difficulty of its eradication, and the deficiency of evil is also a factor leading to drug resistance. In recent years, due to the increase of drug resistance of H. pylori, the research of new anti-H. pylori drugs has become an important research topic. Scholars at home and abroad have started to screen new anti-H. pylori active substances from natural products in the hope of opening a new avenue for the treatment of H. pylori infection. For example, garlic, tea, wine, honey, polysaccharide, ginseng and many other natural products have good anti-H. pylori effects. Previous studies have confirmed (15) that Chinese herbal medicines such as Scutellaria baicalensis, Huanglian, Rhubarb, Honeysuckle, Dandelion, Phellodendron, Ocimum sanctum, Tigris, Atractylodes, Cinnamomum, Gaultheria, Zingiber officinale, Qinpi, Xuanhu, Panax notoginseng, Chebulan, and Baiguo all have good anti-H. pylori effects. In vitro experiments of the compound herbal medicine showed that the oral solution of monkey head mushroom could inhibit Hp-stimulated TNF- production and had antioxidant ability against lipid peroxidation caused by this bacterium, thus protecting gastric epithelial cells and promoting healing of gastritis. In addition, the oral solution also has a certain effect of stimulating lymphocytes, thus enhancing the immune function of the body to some extent, and ultimately acting as an anti-Hp infection. Xu Yi et al. (17) conducted antibacterial tests on the commonly used formulae for spleen and stomach and the Qing Yu Nourishing Stomach Formula, and the results showed that the highly sensitive Zuo Jin Wan had a minimum inhibitory concentration (MIC) of 1:320, and the moderately sensitive Xiang Lian Wan and Qing Yu Nourishing Stomach Formula had MICs of 1:80 and 1:20, respectively. The results showed that both herbal preparations had certain killing effect on Hp in the selected concentration range, and the bactericidal effect was enhanced with the increase of concentration. Tan Sheng’e, Yu Wenqing, Chu Min, Du Pinghua, Xie Zhenjia, etc.19–23 all conducted experiments on Hp inhibition using Chinese patent medicines. The results showed that these Chinese patent medicines: Ulcers and pain relieving tablets, gastric kang capsules, gastric cure, gastric lingsuo and gastric kang gum pills all had strong Hp inhibitory effects, suggesting that Hp inhibition may be an important mechanism of action in the treatment of Hp-associated gastric diseases. Wang Fang et al.24 investigated the inhibitory effect of Sihuang Tongguang on Hp adhesion, and this experiment showed that Sihuang Tongguang could not only effectively inhibit Hp, but also block the adhesion process of Hp to the epithelial cells of gastric mucosa; it is an excellent formula for the treatment of Hp-related gastric diseases, and also can effectively prevent the infection and recurrence of Hp, which has opened up new ideas and methods for the study of the mechanism of anti-Hp in Chinese medicine. The experiment of Hp inhibition by Chinese herbal medicine compounded by Jiang Zhenming et al. showed that both the stomach-clearing punch and Shuanghuanglian oral solution had antibacterial effects on Hp at certain concentrations (1:1, 1:2, 1:4). Both of the two herbal compounds, which are mainly purgative, have antibacterial effects, which provides a basis for further clinical studies on anti-Hp. We25 achieved better efficacy in the treatment of drug-resistant H. pylori infection clinically by using variant triple therapy plus Chinese herbal medicine to benefit qi and support correctness and clear heat and dampness agents. The combination of Chinese and Western medicine can not only improve the success rate of H. pylori eradication, but also reduce the side effects in Western medicine treatment, which is worth further study. In conclusion, H. pylori is a major killer of human health, but its drug resistance has become more and more prominent in recent years, bringing great difficulties to the eradication of H. pylori, how to control the spread of H. pylori and find more effective eradication methods is still a long way to go.