Generalization of Helicobacter pylori eradication therapy and its future in Japan

After official acceptance of eradication therapy for Helicobacter pylori infected peptic ulcer disease in 2000, this treatment has been generalized as ulcer therapy in Japan. In 2003 the consensus statement of the Japanese Society for Helicobacter Research (JSHR) for Helicobacter pylori infection was presented. According to this statement MALT lymphoma was recommended to treat H. pylori infection because of the efficacy of its out come. Atrophic gastritis was also advised to treat H. pylori infection for the purpose of preventing gastric cancer development. The extra alimentary disease such as idiopathic thrombocytopenic purpura was still under evaluation. In diagnostic method the importance of drug susceptibility test is rising because of the increase of drug resistant H. pylori strain in Japan. The false positive case of urea breath test, the accuracy of new Japanese original serology tests and the stool antigen test are also under investigation. The standard regimen of H. pylori eradication therapy in Japan is proton pomp inhibitor (PPI) + amoxicilin (AMPC) + clarithromycin (CAM). The problem of this regimen is the decrease of eradication rate. The reason of this trend might be increase of CAM resistant strain. JSHR recommended a rescue regimen as PPI + AMPC + metronidazole for the patient whose first eradication therapy was unsuccessful result. The eradication of this second line regimen was reported as about 90%.     

Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report. European Helicobacter Pylori Study Group.

There is considerable confusion over the management of Helicobacter pylori infection, particularly among primary care physicians, and numerous European countries lack national guidelines in this rapidly growing area of medicine. The European Helicobacter Pylori Study Group therefore organised a meeting in Maastricht of H pylori experts, primary care physicians and representatives of National Societies of Gastroenterology from Europe to establish consensus guidelines on the management of H pylori at the primary care and specialist levels, and to consider general health care issues associated with the infection. As in previous guidelines, eradication therapy was recommended in all H pylori positive patients with peptic ulcer disease. Additionally, at the primary care level in dyspeptic patients < 45 years old and with no alarm symptoms, diagnosis is recommended by non-invasive means (13C urea breath test, serology) and if H pylori positive the patient should be treated. Moreover, at the specialist level the indications for eradication of H pylori were also broadened to include H pylori positive patients with functional dyspepsia in whom no other possible causes of symptoms are identified by the specialist (after a full investigation including endoscopy, ultrasound and other necessary investigations), patients with low grade gastric mucosa associated lymphoid tissue (MALT) lymphoma (managed in specialised centres) and those with gastritis with severe macro- or microscopic abnormalities. There was consensus that treatment regimens should be simple, well tolerated and achieve an eradication rate of over 80% on an intention to treat basis. It was strongly recommended, therefore, that eradication treatment should be with proton pump inhibitor based triple therapy for seven days, using a proton pump inhibitor and two of the following: clarithromycin, a nitroimidazole (metronidazole or tinidazole) and amoxycillin.     

Treatment of Helicobacter pylori

Triple therapy, consisting of two antibiotics, clarithomycin and amoxicillin or metronidazole in combination with a proton pump inhibitor (PPI) has become the first-line option for infection with Helicobacter pylori and has been recommended at several consensus conferences. In clinical practice, approximately 20% of patients will fail to obtain H. pylori eradication with the recommended treatment regimens. Major causes of treatment failure are insufficient patient compliance and antibiotic resistance. Because of antibiotic resistance, bismuth-based quadruple therapy has also become a first-line regimen in areas with exceedingly high rates of clarithromycin and metronidazole resistance, and is the preferred second-line option otherwise. Triple therapies based on levofloxacin and/or rifabutin mainly with combination of amoxicillin are options if multiple eradication failure occurs. However, following therapy failure beyond a second treatment attempt requires antibiotic resistance testing. New drugs and adjuvant agents have been reported but their efficacy needs further evaluation.     

药敏试验在三联疗法根除幽门螺杆菌中的作用

背景：近年幽门螺杆菌（H．pylori）对硝基咪唑类和大环内酯类抗生素的耐药率快速增高,导致目前推荐的H．p？tori根除方案疗效降低。目的：观察体外实验中Hpylori对甲硝唑和克拉霉素的敏感性,评估药敏试验基础上的个体化治疗方案能否提高根除率。方法：对260例连续Hpylori阳性患者的内镜胃窦部活检标本行H．pylori培养和药敏试验。患者随机分为两组,A组（n=135）使用奥美托唑、甲硝唑和克拉霉素治疗10d,B组（n=125）在药敏试验的基础上接受10d个体化治疗。治疗结束1个月后．根据14C-尿素呼气试验结果评价根除率。结果：共248例患者（A组129例,B组119例）完成治疗和疗效评价,甲硝唑、克拉霉素单一和联合耐药率分别为31．0％、11．7％和3．6％。A组按方案（PP）分析和意向治疗（ITT）分析的H．pylori根除率分别为82．9％和79．3％,B组分别为98.3％和93．6％,B组根除率显著高于A组（P〈0．01）。结论：药敏试验基础上的个体化治疗可有效提高H．pylori的根除率。     

Comparison of the effectiveness of quadruple salvage regimen for Helicobacter pylori infection according to the duration of treatment]

BACKGROUND/AIMS: At present, triple therapy schemes are recommended by national and international consensus conferences for the treatment of Helicobacter pylori (H. pylori) infection. However, even with the most effective current treatment regimens, about 10-20% of patients fail to eradicate H. pylori, necessitating alternative strategy to eradicate H. pylori in primary treatment failure. Therefore, we performed this study to evaluate the efficacy of quadruple therapy and to compare 1 and 2-week quadruple regimen as a second-line therapy. METHODS: The hospital records of 155 patients who failed to the standard triple therapy (proton pump inhibitor, amoxicillin, clarithromycin) were reviewed retrospectively, and divided the 1 or 2 weeks OBMT regimen (omeprazole 20 mg bid, bismuth salt 120 mg qid, metronidazole 500 mg tid, tetracycline 500 mg qid). Presence of H. pylori infection and side-effects of the treatment regimen were assessed 4 weeks after the cessation of treatment. RESULTS: One hundred and eight male and 47 female (mean age, 52.2+/-15.4) patients were enrolled. The overall eradication rate of H. pylori with quadruple therapy was 83.9% and the eradication rate was similar between 1 and 2 weeks of OBMT regimen (76.8% in OBMT 1 week, 87.9% in OBMT 2 weeks, respectively p=0.110). CONCLUSIONS: Quadruple therapy is an effective salvage regimen for H. pylori eradication after the failure of standard triple therapy. One week quadruple therapy is not significantly different from 2-weeks regimen as the second-line option for H. pylori eradication.     

Relationship between eradication therapy and clarithromycin-resistant Helicobacter pylori in Japan

Since clarithromycin is expected to be widely used to treat Helicobacter pylori infection in the near future, it is important to investigate the relationship between resistance to clarithromycin and the regimens of eradication therapy. We investigated: (1) the usefulness of susceptibility tests prior to eradication therapy, and (2) the rate of acquisition of H. pylori resistance to clarithromycin after treatment failure. Drug susceptibility tests to clarithromycin and amoxicillin were conducted by Dry Plate Test or E-test. The subjects in the first part of this study included 112 patients with H. pylori infection who received triple therapy with various combinations of drugs, including clarithromycin. The eradication rate in patients with clarithromycin-susceptible H. pylori was significantly higher than that in patients with clarithromycin-resistant H. pylori. The second part of this study included 21 patients in whom H. pylori was not eradicated by triple therapy and 12 patients in whom H. pylori was not eradicated with dual therapy including clarithromycin. Of the 33 patients showing non-eradication. 90.9% of those treated with dual therapy and 35.7% of those treated with triple therapy acquired secondary resistance of H. pylori to clarithromycin. We conclude that it is important to conduct drug susceptibility tests prior to treatment of H. pylori infection. Since the incidence of acquiring clarithromycin resistance was significantly higher in the patients showing non-eradication, it is important to choose a regimen with a higher eradication rate, such as triple therapy.     

Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report

BACKGROUND: Guidelines on the management of Helicobacter pylori, which cover indications for management and treatment strategies, were produced in 2000. AIMS: To update the guidelines at the European Helicobacter Study Group (EHSG) Third Maastricht Consensus Conference, with emphasis on the potential of H pylori eradication for the prevention of gastric cancer. RESULTS: Eradication of H pylori infection is recommended in (a) patients with gastroduodenal diseases such as peptic ulcer disease and low grade gastric, mucosa associated lymphoid tissue (MALT) lymphoma; (b) patients with atrophic gastritis; (c) first degree relatives of patients with gastric cancer; (d) patients with unexplained iron deficiency anaemia; and (e) patients with chronic idiopathic thrombocytopenic purpura. Recurrent abdominal pain in children is not an indication for a "test and treat" strategy if other causes are excluded. Eradication of H pylori infection (a) does not cause gastro-oesophageal reflux disease (GORD) or exacerbate GORD, and (b) may prevent peptic ulcer in patients who are na?ve users of non-steroidal anti-inflammatory drugs (NSAIDs). H pylori eradication is less effective than proton pump inhibitor (PPI) treatment in preventing ulcer recurrence in long term NSAID users. In primary care a test and treat strategy using a non-invasive test is recommended in adult patients with persistent dyspepsia under the age of 45. The urea breath test, stool antigen tests, and serological kits with a high accuracy are non-invasive tests which should be used for the diagnosis of H pylori infection. Triple therapy using a PPI with clarithromycin and amoxicillin or metronidazole given twice daily remains the recommended first choice treatment. Bismuth-containing quadruple therapy, if available, is also a first choice treatment option. Rescue treatment should be based on antimicrobial susceptibility. CONCLUSION: The global burden of gastric cancer is considerable but varies geographically. Eradication of H pylori infection has the potential to reduce the risk of gastric cancer development.     

Helicobacter pylori eradication therapy in Korea

Helicobacter pylori (H. pylori) is known to be associated with many gastrointestinal diseases including peptic ulcer. In Korea, eradication of H. pylori is recommended for peptic ulcer disease, low grade gastric mucosa-associated lymphoid tissue lymphoma, and early gastric cancer. Standard triple therapy using proton pump inhibitor, clarithromycin, and amoxicillin and bismuth-containing quadruple therapy have been the main first-line and second-line therapy for H. pylori in Korea. Although eradication rate of second-line quadruple therapy remains similar to that of the past, the success rate of eradication with triple therapy has decreased with increasing antimicrobial resistance to H. pylori. There is no standard third-line therapy, and some regimens that incorporate levofloxacin, moxifloxacin, and rifabutin can be used. New regimens such as sequential or concomitant therapy are suggested as alternative treatment for H. pylori. We need more well designed randomized controlled studies to choose proper treatment for H. pylori infection.     

Second Asia–Pacific Consensus Guidelines for Helicobacter pylori infection

The Asia–Pacific Consensus Conference was convened to review and synthesize the most current information on Helicobacter pylori management so as to update the previously published regional guidelines. The group recognized that in addition to long-established indications, such as peptic ulcer disease, early mucosa-associated lymphoid tissue (MALT) type lymphoma and family history of gastric cancer, H. pylori eradication was also indicated for H. pylori infected patients with functional dyspepsia, in those receiving long-term maintenance proton pump inhibitor (PPI) for gastroesophageal reflux disease, and in cases of unexplained iron deficiency anemia or idiopathic thrombocytopenic purpura. In addition, a population 'test and treat' strategy for H. pylori infection in communities with high incidence of gastric cancer was considered to be an effective strategy for gastric cancer prevention. It was recommended that H. pylori infection should be tested for and eradicated prior to long-term aspirin or non-steroidal anti-inflammatory drug therapy in patients at high risk for ulcers and ulcer-related complications. In Asia, the currently recommended first-line therapy for H. pylori infection is PPI-based triple therapy with amoxicillin/metronidazole and clarithromycin for 7 days, while bismuth-based quadruple therapy is an effective alternative. There appears to be an increasing rate of resistance to clarithromycin and metronidazole in parts of Asia, leading to reduced efficacy of PPI-based triple therapy. There are insufficient data to recommend sequential therapy as an alternative first-line therapy in Asia. Salvage therapies that can be used include: (i) standard triple therapy that has not been previously used; (ii) bismuth-based quadruple therapy; (iii) levofloxacin-based triple therapy; and (iv) rifabutin-based triple therapy. Both CYP2C19 genetic polymorphisms and cigarette smoking can influence future H. pylori eradication rates.     

Treatment of Helicobacter pylori infection. Indications and regimens: an update.

The management of Helicobacter pylori infection is still surrounded by controversy and uncertainties. Indications and correct application of current regimens for Helicobacter pylori infection are still considered a matter of debate. Regarding indications, only peptic ulcer and mucosa associated lymphoid tissue lymphoma are considered clear indications for treatment. In other conditions, such as atrophic gastritis, post gastric cancer resection, first-degree relatives of gastric cancer patients, dyspeptic patients, patients with gastro-oesophageal reflux disease and non-steroidal anti-inflammatory drug users, the value of Helicobacter pylori eradication is still controversial. The regimens for first-line and second-line treatment of Helicobacter pylori infection have been recommended by the Maastricht 2 Consensus Report. Although all the treatments are considered to be effective, physicians still do not agree on what first-line regimen should be used. Furthermore, a consensus on the duration of the antibiotic treatment is still lacking, although Maastricht guidelines for treatment of Helicobacter pylori infection recommend a one-week therapy. Also regimens, as a third-line treatment, and methods to improve compliance and clinical outcome are still a matter of debate. All these points will be considered in the present review     

Cost-Effectiveness of Treatment Regimens for the Eradication of Helicobacter pylori in Duodenal Ulcer

Background: Eradication of Helicobacter pylori with antimicrobials was recommended by a recent NIH consensus panel for all infected patients with peptic ulcer disease. The precise regimen that should be used for eradication of the infection remains uncertain because of the variety of regimens described, variable results with the regimens, and difficulties in predicting drug compliance outside clinical trials. Methods: A decision analysis tree was developed with three regimens that are widely used regimens for the eradication of H. pylori: 1 ) 2-wk triple drug therapy (metronidazole, bismuth, tetracycline with H2 receptor antagonist), 2) 2-wk omeprazole and amoxicillin, and 3) 2-wk omeprazole and clarithromycin. Traditional H2 receptor antagonist therapy was used for comparison. A 2-yr time period was chosen for study to allow sufficient time for relapse and to evaluate its effect on the treatment strategy. Probabilities for eradication, compliance, and metronidazole resistance were determined from published data, and assumptions were tested by sensitivity analysis. Results: Standard 2-wk triple drug therapy was the least expensive strategy ($720), and conventional H2 receptor antagonist therapy was the most expensive ($1791). Costs with 2-wk therapy with omeprazole and clarithromycin ($768) were lower than with omeprazole and amoxicillin ($1028). Conclusions. Treatment to eradicate H. pylori in infected patients with duodenal ulcer is a less expensive strategy than traditional therapy with H2 receptor antagonists. Triple drug therapy is the optimal regimen in areas where metronidazole resistance rates are <36% and compliance is >53%. Omeprazole and amoxicillin is not cost-effective unless eradication rates are greater than 74%. Dual drug therapy with omeprazole and clarithromycin is effective in regions where metronidazole resistance is high or where it is anticipated that there would be poor compliance with the more complicated triple drug therapy regimen.     

Antimicrobial susceptibility of Helicobacter pylori isolates of dyspeptic Nigerian patients.

The resistance of Helicobacter pylori to antibiotic treatment is a growing global concern, but this has not been well studied in our environment. This study sought to determine: the susceptibility of the organism to common antimicrobial agents used in its eradication therapy. Twenty H. pylori isolates from dyspeptic patients were subjected to standard procedures for sensitivity testing and the determination of minimum inhibitory concentration against amoxycillin, ciprofloxacin, clarithromycin, erythromycin, metronidazole, rifampicin and tetracycline. The study showed marked in vitro multiple antimicrobial resistance to the commonly used eradication agents. All twenty isolates were however sensitive to ciprofloxacin. The findings of marked antimicrobial resistance may affect the effectiveness of currently recommended eradication regimes. In our environment, incorporating ciprofloxacin into the existing H. pylori antimicrobial therapy may improve the outcome of eradication.     

Ranitidine bismuth citrate.

Recognition of the relationship between Helicobacter pylori infection and the development of gastroduodenal disease has increased greatly in recent years. To avoid complications of H pylori infection, such as the development of recurrent duodenal and gastric ulcers, effective therapies are required for eradication of the infection. This article reviews ranitidine bismuth citrate (RBC), a novel complex of ranitidine, bismuth and citrate, which was developed specifically for the purpose of eradicating H pylori. Dual therapy with RBC in combination with clarithromycin for 14 days yields eradication rates of 76%. Triple therapy bid for one week with a proton pump inhibitor, clarithromycin and either amoxicillin or a nitroimidazole (tinidazole or metronidazole) is advocated as the treatment of choice for H pylori eradication. Analogous regimens with RBC in place of proton pump inhibitors show effective eradication rates in comparative studies and with pooled data. RBC, used alone or in combination with other antibiotics, appears to be a safe and effective drug for the treatment of H pylori infection. Bismuth levels do not appear to rise to toxic levels.     

Future candidates for indications of Helicobacter pylori eradication: Do the indications need to be revised?

Since the discovery of Helicobacter pylori in 1982, the development of several treatment guidelines has allowed a consensus on the indications for H. pylori eradication. Beyond these currently accepted indications, including various upper gastrointestinal disorders and extragastric diseases, a significant amount of new information regarding H. pylori eradication is emerging. Certain types of acute gastritis, such as nodular gastritis, hypertrophic gastritis, Ménétrier's disease, hemorrhagic gastritis, and granulomatous gastritis are reversible after H. pylori eradication. Further, for chronic gastritis, closed-type atrophic gastritis and complete-type intestinal metaplasia appear to be more reversible after H. pylori eradication than open-type atrophic gastritis and incomplete-type intestinal metaplasia. Eradication can also be considered in subjects younger than 40 years who have a family history of gastric cancer and in subjects with long-term medications that might lead to bleeding (antiplatelet agents) or atrophy (proton pump inhibitors). Emerging evidence indicates that H. pylori eradication could be an effective treatment for some extragastric diseases that are unresponsive to conventional therapy. In such conditions, routine screening for eradication of H. pylori has not previously been recommended; a "test-and-treat" approach is suggested in the aforementioned situations. Given that H. pylori eradication is effective when the gastritis is reversible, future indications should be expanded to include acute gastric lesions that show marked improvement upon H. pylori eradication rather than just focusing on chronic gastric lesions. Future indications for H. pylori eradication should focus more on reversible lesions before preneoplastic conditions develop.     

Helicobacter pylori treatment: a practical approach

The treatment of Helicobacter pylori infection has become complicated by the lack of new treatment regimens and the emergence of drug resistant strains of H. pylori. Metronidazole and clarithromycin resistance are common in developed countries. Eradication rates have been falling in trials and in clinical practice around the world. A practical approach to the treatment of patients with H. pylori infection and those who fail initial eradication therapy is discussed.     

Update on the role of H pylori infection in gastrointestinal disorders.

Infection with Helicobacter pylori is accepted as the primary cause of peptic ulcer disease, and there is evidence to suggest its role in other gastrointestinal disorders. An estimated 20% to 40% of the Canadian population is infected with H pylori; however, clinically relevant disease is present in only approximately 10% to 20% of these individuals. Therefore, it is crucial to identify the diseases for which eradication of H pylori is beneficial to ensure that patients do not receive unnecessary treatment. In patients with ulcers induced by long term treatment with nonsteroidal anti-inflammatory drugs, preliminary results suggest that eradication of H pylori may reduce the risk of peptic ulcer bleeding. Furthermore, a benefit has been observed for the eradication of H pylori before patients commence therapy with a nonsteroidal anti-inflammatory drug. An association between the presence of H pylori and specific dyspeptic symptoms has yet to be established; however, there may be a subset of patients with functional dyspepsia who benefit from the eradication of H pylori. The relationship between gastroesophageal reflux disorder and H pylori infection remains unclear. In Canada, the recommended therapy for the eradication of H pylori is seven days of twice-daily treatment with a proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole. Although the proton pump inhibitors are treated as a class for use in these regimens, there is suggestion that a faster onset of action may lead to a higher rate of eradication.     

Recent success of pantoprazole -or lansoprazole- based clarithromycin plus amoxicillin treatment in the eradication of Helicobacter pylori.

BACKGROUND/AIMS: There are some reports showing that resistance of Helicobacter pylori (H. pylori) to clarithromycin has increased in recent years. We aimed to investigate the current success of a most popular first-line eradication regimen by using two different proton pump inhibitors: lansoprazole and pantoprazole. METHODS: Ninety patients with H. pylori-positive functional dyspepsia were randomized to receive pantoprazole 40 mg b.i.d. or lansoprazole 30 mg b.i.d. in addition to amoxicillin 1,000 mg and clarithromycin 500 mg twice daily for 14 days in a multicenter study. H. pylori infection was determined by histological examination and a rapid urease test. A follow-up endoscopy was performed to assess the H. pylori eradication six weeks after the end of therapy. RESULTS: Seventy-nine patients completed the study protocol properly. The H. pylori eradication rates according to per protocol analysis were 70% in group pantoprazole, amoxicillin and clarithromycin (28/40) and 69.2% in group pantoprazole, amoxicillin and clarithromycin (27/39). The eradication rates according to intention to treat analysis were 62.2% and 60% in lansoprazole, amoxicillin, clarithromycin, pantoprazole, amoxicillin, clarithromycin groups, respectively. The eradication rates were similar in both protocols (p>0.05). CONCLUSIONS: The most popular first-line eradication protocols of H. pylori achieved only a moderate success in the current study. Alternative therapy options are needed instead of clarithromycin-based triple treatment for eradication of H. pylori. The choice of proton pump inhibitor is not important in the eradication rate of H. pylori.     

Treatment of Helicobacter pylori infection]

Significant progress and new insights have been gained since Helicobacter pylori was found in 1982. Even with currently most effective treatment regimen, about 10-20% of patients will fail to obtain the eradication of H. pylori infection. This review will focus on the empirical treatment for H. pylori infection in Korea. Seven days triple therapy (proton pump inhibitor, amoxicillin and clarithromycin) has been the main first line therapy for H. pylori infection in Korea after the recommendation by Korean H. pylori study group in 1998. Such triple therapy has been the effective regimen for eradication of H. pylori infection. However, the efficacy of 7 days proton pump inhibitor-amoxicillin-clarithromycin therapy becomes lower and various eradication rates probably reflects the increase in antimicrobial resistance, recently. The recent multi-center prospective randomized study and meta-analysis showed 14 days proton pump inhibitor-amoxicillin-clarithromycin therapy is more effective than 7 days or 10 days therapy. In the case of failure, quadruple therapy (proton pump inhibitor, a bismuth salt, metronidazole and tetracycline) is a very effective second-line regimen. After the failure of two or more eradication treatments, bacterial resistance to antibiotics should be evaluated and the regimen of third-line therapy should be selected according to each antimicrobial susceptibility. The empirical third-line therapies, recommended in the cases that antimicrobial susceptibility test is unavailable, are unclear of its validity at present in Korea. The triple therapies including rifabutin, moxifloxacin, or levofloxacin or dual therapy including high dose proton pump inhibitor and amoxicillin are needed to be proven as possible candidates for the empirical third-line therapy. Multiple eradication failures should be handled on a case-by-case basis by specialists.     

Canadian Helicobacter Study Group Consensus Conference: Update on the management of Helicobacter pylori--an evidence-based evaluation of six topics relevant to clinical outcomes in patients evaluated for H pylori infection.

As an update to previously published recommendations for the management of Helicobacter pylori infection, an evidence-based appraisal of six topics was undertaken in a consensus conference sponsored by the Canadian Helicobacter Study Group. The issues addressed and recommendations made were: bismuth-containing quadruple therapy is appropriate as an alternative first-line eradication strategy for H pylori infection; searching for and treating H pylori infection is warranted in patients considered to be at high risk for gastric cancer; H pylori infection should be eradicated before initiating long-term treatment with nonsteroidal anti-inflammatory drugs or acetylsalicylic acid; the stool antigen test has a limited role in the diagnosis of H pylori infection; the benefits of H pylori eradication in patients on long-term proton pump inhibitor therapy are not sufficient to warrant recommending a strategy of searching for and eradicating the infection among these patients; and a strategy of "test and eradicate" for H pylori infection in patients with uninvestigated dyspepsia is cost-effective in Canada relative to a trial of proton pump inhibitor therapy. The goal was to establish guidelines on the best evidence using the same structure to address and formulate recommendations for each issue. The degree of consensus for each issue is presented.     

Third-line rescue therapy for Helicobacter pylori infection

H pylori gastric infection is one of the most prevalent infectious diseases worldwide. The discovery that most upper gastrointestinal diseases are related to H pylori infection and therefore can be treated with antibiotics is an important medical advance. Currently, a first-line triple therapy based on proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) plus two antibiotics (clarithromycin and amo-xicillin or nitroimidazole) is recommended by all consensus conferences and guidelines. Even with the correct use of this drug combination, infection can not be eradicated in up to 23% of patients. Therefore, several second line therapies have been recommended. A 7 d quadruple therapy based on PPI, bismuth, tetracycline and metronidazole is the more frequently accepted. However, with second-line therapy, bacterial eradication may fail in up to 40% of cases. When H pylori eradication is strictly indicated the choice of further treatment is controversial. Currently, a standard third-line therapy is lacking and various protocols have been proposed. Even after two consecutive failures, the most recent literature data have demonstrated that H pylori eradication can be achieved in almost all patients, even when antibiotic susceptibility is not tested. Different possibilities of empirical treatment exist and the available third-line strategies are herein reviewed.