Attitude facing a patient suffering from Helicobacter pylori infection resistant to a triple therapy.

Even with the current most effective treatment regimens, about 10-20% of patients will fail to eradicate H. pylori infection. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final (over-all) eradication rate. The choice of a second-line treatment depends on which treatment was used initially, as retreatment with the same regimen is not recommended. In this respect, the first therapy should not be a regimen that combines clarithromycin and metronidazole in the same regimen, because of the problem of resistance against both antibiotics. Therefore, it seems that performing culture after a first eradication failure is not necessary and assessing H. pylori sensitivity to antibiotics only after failure of the second treatment may be suggested in clinical practice. Different possibilities of empirical treatment are suggested. After failure of proton pump inhibitor (PPI)-amoxicillin-clarithromycin, quadruple therapy has been generally used. More recently, replacing the PPI and the bismuth compound by ranitidine bismuth citrate (RBC) has also achieved good results. After PPI-amoxicillin-nitroimidazole failure, retreatment with PPI-amoxicillin-clarithromycin has proved to be effective. Finally, rifabutin-based rescue therapies have shown to constitute an encouraging strategy for eradication failures, as they are effective for H. pylori strains resistant to antibiotics.     

Efficacy of quadruple therapy for Helicobacter pylori eradication after failure of proton pump inhibitor‐based triple therapy in Singapore

BACKGROUND: Helicobacter pylori eradication is the mainstay in the treatment of H. pylori‐associated peptic ulcer disease. Current standard eradication therapy consists of 1 week of treatment with a proton pump inhibitor (PPI) and two antibiotics selected from amoxicillin, metronidazole and clarithromycin. In this study we aimed to assess the efficacy of quadruple therapy consisting of a PPI, bismuth, tetra‐cycline and metronidazole in patients for whom initial H. pylori eradication using a triple therapy regimen consisting of a PPI, amoxicillin and clarithromycin was unsuccessful. METHODS: Consecutive patients with H. pylori‐associated peptic ulcer disease, in whom H. pylori with triple therapy had been unsuccessful, were included in the study. These patients had been treated with a regimen that included a PPI (standard dose twice daily), amoxicillin (1 g twice daily) and clarithro­mycin (500 mg twice daily) for 1 week during 1997?2001. Diagnosis of peptic ulcer disease was made at esophagogastroduodenoscopy. Helicobacter pylori infection was considered to be present on the basis of either a positive rapid urease test, positive histo­logical identification of H. pylori or both. Failure of initial H. pylori eradication was established with either a rapid urease test, a ¹³C urea breath test or histology. Quadruple therapy consisted of a PPI (standard dose twice daily), metronidazole (400 mg three times daily), tetracycline (500 mg four times daily) and bismuth subcitrate (240 mg twice daily). Failure of quadruple therapy was diagnosed on the basis of a positive ¹³C urea breath test. RESULTS: Fifty‐three patients received quadruple therapy. The median age was 52 years (range 20?74) and the male to female ratio was 42 : 11. On an intent‐to‐treat basis, the eradication rate was 69.8%, whereas on a per‐protocol basis, the eradication rate was 82.2%. CONCLUSION: We conclude that a 1‐week quadruple therapy regime consisting of a PPI, bismuth, tetracycline and metronidazole was effective in 82.2% of patients who experienced an unsuccessful initial H. pylori eradication attempt with PPI, amoxicillin and clarithromycin.     

Susceptibility-Guided vs. Empiric Retreatment of Helicobacter pylori Infection After Treatment Failure

Successful eradication of Helicobacter pylori after failure of standard triple therapy is difficult because of the higher resistance to metronidazole and clarithromycin. We evaluated the efficacy of susceptibility-guided vs. empiric retreatment for H. pylori after at least one treatment failure and determined the prevalence of posttreatment antibiotic resistance. Forty-nine patients in whom at least one treatment regimen for H. pylori eradication had failed underwent gastric biopsy and culture and were retreated according to the in vitro susceptibility results. Findings were compared with those for 49 control patients referred to our center for a ¹³C-urea breath test. H. pylori eradication was assessed by urea breath test at least 6 weeks after retreatment in both groups. Susceptibility-guided retreatment was associated with better eradication rates than empiric treatment. The difference remained significant in stratified and multivariate analysis. Susceptibility-guided retreatment appears to be significantly more effective than empiric retreatment in eradicating H. pylori after at least one previous treatment failure.     

Update on therapeutic options for <Emphasis Type="Italic">Helicobacter pylori</Emphasis>-related diseases

Triple therapy including clarithromycin, amoxicillin, and a proton pump inhibitor (PPI) has been recommended as the treatment of choice for Helicobacter pylori eradication. This regimen is now challenged by an increasing level of clarithromycin resistance that jeopardizes the treatment success. When clarithromycin resistance has been detected, or when its rate is known to be high in the geographic area, this drug cannot be used. It can be replaced by metronidazole, the resistance of which has a limited clinical relevance. Another option is to prescribe tetracycline and metronidazole with a PPI or ranitidine bismuth citrate. New antibiotics such as levofloxacin or rifabutin can also be used in combination with amoxicillin and a PPI. Probiotics can be added to all of these regimens to improve compliance by decreasing adverse events. But some authors advocate a quadruple therapy as a first-line treatment. Solutions to improve the limitations of this last regimen are now being proposed. Clarification of the controversial treatment indications such as gastroesophageal reflux disease or prevention of nonsteroidal anti-inflammatory drug gastroduodenal symptoms has been made. The question of prevention of gastric carcinoma by H. pylori eradication remains unanswered.     

How to proceed in Helicobacter pylori-positive chronic gastritis refractory to first- and second-line eradication therapy

Helicobacter pylori is a widespread disease causing most of the peptic ulcer diseases and low-grade mucosa-associated lymphoreticular tissue (MALT) lymphoma. Moreover, H. pylori is a proven environmental risk factor for gastric carcinoma and it has been recognized as a type 1 carcinogen factor. A combination of drugs has been proposed, using a proton pump inhibitor (PPI), amoxicillin, clarithromycin, metronidazole and tetracycline to treat the infection. Since 1996, according to the European guidelines, the first-line approach using PPI, amoxicillin and clarithromycin or metronidazole has been suggested. Seven days of quadruple therapy with PPI (or ranitidine), tetracycline, bismuth salts and metronidazole has been reserved as second-line treatment. To improve the eradication rate of the triple therapy, a different combination of the available antibiotics has been proposed, consisting of a 10-day sequential regimen. A second-line levofloxacin-amoxicillin-based triple therapy given for 10 days has been proposed, obtaining a high eradication rate, suggesting this regimen to be a suitable retreatment option in eradication failure. A third-line treatment with rifabutin-based regimen has been proposed.     

'Rescue' therapies for the management of Helicobacter pylori infection

Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer and gastric cancer and should be considered as a major public health issue. According to several international guidelines, first-line therapy for treating H. pylori infection consists of proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) with any two antibiotics of amoxicillin, clarithromycin or metronidazole given for 7-14 days. However, even with the recommended treatment regimens, approximately 20% of patients will fail to obtain H. pylori eradication. The proportion of patients with first-line H. pylori therapy failure may be higher in clinical practice and it may increase thanks to diffusion of H. pylori treatment. The recommended second-line therapy is the quadruple regimen composed by tetracycline, metronidazole, bismuth salts and a PPI. However, the efficacy of this regimen is limited by poor patient's compliance due to its side effects, number of tablets per day, and long duration. Moreover, bismuth and metronidazole are not available in all countries. Alternatively, a longer-lasting (i.e. 10-14 days) PPI or RBC triple therapy with two antibiotics has generally been used. In an empirical strategy, the choice of second line depends on the treatment initially used. If a clarithromycin-based regimen was administered in first line, a quadruple regimen or PPI (or RBC) triple therapy with metronidazole and amoxicillin (or tetracycline) should be suggested as a second line. In case of second-line treatment failure, the patient should be evaluated by a case-by-case approach. A susceptibility-guided strategy, if available, is recommended in order to choose the best third-line treatment. Culture can reveal the presence of H. pylori-sensitive strains to clarithromycin (the best effective) or other antimicrobials (such as amoxicillin, metronidazole and tetracycline). Conversely, in an empirical strategy, a third-line not yet used therapy, can reach a high success rate. PPI or RBC, amoxicillin and a new antimicrobial (e.g. rifabutin, levofloxacin or furazolidone) could be used. Several studies have obtained relatively good results with triple therapy combining PPI, rifabutin, and amoxicillin, although a reversible myelotoxicity as leukopenia and thrombocytopenia has been described. Preliminary good results were also achieved with triples PPI regimens combining levofloxacin and amoxicillin without important adverse effects. Furazolidone has also shown efficacy for H. pylori eradication, although untoward reactions could limit its use, especially when high doses are employed. Finally, in more than one H. pylori treatment failure, non-antimicrobial add-on medications (such as lactoferrin, probiotics and others) could be used with the aim either to improve the eradication rate or to minimize side effects.     

Treatment of Helicobacter pylori infection:Current status and future concepts

Helicobacter pylori(H.pylori)infection is highly associated with the occurrence of gastrointestinal diseases,including gastric inflammation,peptic ulcer,gastric cancer,and gastric mucosa-associated lymphoid-tissue lymphoma.Although alternative therapies,including phytomedicines and probiotics,have been used to improve eradication,current treatment still relies on a combination of antimicrobial agents,such as amoxicillin,clarithromycin,metronidazole,and levofloxacin,and antisecretory agents,such as proton pump inhibitors(PPIs).A standard triple therapy consisting of a PPI and two antibiotics(clarithromycin and amoxicillin/metronidazole)is widely used as the first-line regimen for treatment of infection,but the increased resistance of H.pylori to clarithromycin and metronidazole has significantly reduced the eradication rate using this therapy and bismuth-containing therapy or 10-d sequential therapy has therefore been proposed to replace standard triple therapy.Alternatively,levofloxacin-based triple therapy can be used as rescue therapy for H.pylori infection after failure of first-line therapy.The increase in resistance to antibiotics,including levofloxacin,may limit the applicability of such regimens.However,since resistance of H.pylori to amoxicillin is generally low,an optimized high dose dual therapy consisting of a PPI and amoxicillin can be an effective first-line or rescue therapy.In addition,the concomitant use of alternative medicine has the potential to provide additive or synergistic effects against H.pylori infection,though its efficacy needs to be verified in clinical studies.     

High antibiotic resistance rate: A difficult issue for Helicobacter pylori eradication treatment

Helicobacter pylori (H. pylori) infection is associated with a variety of upper gastrointestinal diseases, including gastric cancer. With the wide application of antibiotics in H. pylori eradication treatment, drug-resistant strains of H. pylori are increasing. H. pylori eradication treatment failure affects the outcome of a variety of diseases of the upper gastrointestinal tract. Therefore, antibiotic resistance that affects H. pylori eradication treatment is a challenging situation for clinicians. The ideal H. pylori eradication therapy should be safe, effective, simple, and economical. The eradication rate of triple antibiotic therapy is currently less than 80% in most parts of the world. Antibiotic resistance is the main reason for treatment failure, therefore the standard triple regimen is no longer suitable as a first-line treatment in most regions. H. pylori eradication treatment may fail for a number of reasons, including H. pylori strain factors, host factors, environmental factors, and inappropriate treatment.     

Helicobacter pylori therapy: first-line options and rescue regimen

In the present paper, several points regarding Helicobacter pylori treatment are reviewed, with the following conclusions: (1) all different proton pump inhibitors (PPIs) are equivalent when prescribed with antibiotics; (2) ranitidine bismuth citrate is equal to or, in some cases with antibiotic resistance, more effective than PPI; (3) previous treatment with PPI does not seem to affect the rate of eradication obtained with PPI plus two antibiotics; (4) just 1 week of PPI is enough to obtain duodenal ulcer healing, provided that H. pylori eradication is achieved; (5) the eradication rates seem to be higher in peptic ulcer than in nonulcer dyspepsia; (6) in areas where the prevalence of metronidazole resistance is high, triple therapy including a PPI, clarithromycin, and amoxicillin is the best option, and (7) quadruple therapy (PPI, bismuth, tetracycline, and metronidazole) is the recommended second-line therapy after PPI-clarithromycin-amoxicillin failure, although replacing the PPI and the bismuth compound by ranitidine bismuth citrate achieves also good results.     

Efficacy of a 7-day course of furazolidone, levofloxacin, and lansoprazole after failed Helicobacter pylori eradication

Background  

Increasing resistance to clarithromycin and nitroimidazole is the main cause of failure in the Helicobacter pylori eradication. The ideal retreatment regimen remains unclear, especially in developing countries, where the infection presents high prevalence and resistance to antibiotics. The study aimed at determining the efficacy, compliance and adverse effects of a regimen that included furazolidone, levofloxacin and lansoprazole in patients with persistent Helicobacter pylori infection, who had failed to respond to at least one prior eradication treatment regimen.     

Diagnosis and treatment of <Emphasis Type="Italic">Helicobacter pylori</Emphasis>

Opinion statement Helicobacter pylori infection remains a ubiquitous infection, especially in populations with poor socioeconomic conditions. Severe clinical outcomes of chronic infection include peptic ulcer disease and gastric cancer. Consensus meetings have developed guidelines for diagnosis, treatment, and management of H. pylori infection and related disorders in various populations. Clear benefits are obtained for H. pylori eradication in peptic ulcer disease and gastric mucosa-associated lymphoid tissue lymphoma. Most authorities agree that first-degree relatives of gastric cancer patients should undergo testing for H. pylori infection. H. pylori eradication in dyspepsia remains controversial. Global investigations continue to identify specific host and bacterial factors that are responsible for H. pylori-related inflammatory processes and development of clinical disease. Effective eradication regimens have been identified. The proton pump inhibitor (PPI)-based triple therapies are considered first-line therapy because of high patient compliance and good eradication rates. “Quadruple therapy” with bismuth-metronidazoletetracycline plus a PPI is another first-line therapy with a similar eradication rate. This therapy is preferred in patients with penicillin allergy or prior exposure to clarithromycin. Rescue regimens are being developed because of rising antimicrobial resistance to metronidazole and clarithromycin in H. pylori strains. Emerging rescue combination therapies include furazolidone, rifabutin, and quinolones. These combination regimens are still preliminary and should be reserved for patients who have failed first-line therapies. Vaccine development remains elusive.     

Rescue therapy after Helicobacter pylori eradication failure

Despite the use of currently-recommended therapies, at least 20% of patients remain infected after a first attempt at Helicobacter pylori eradication. Therefore, when designing a therapeutic strategy, rather than focus exclusively on the result of the first eradication therapy, from the outset physicians should plan the sequence of consecutively administered combinations with the highest possibility of achieving a 100% success rate. The choice of rescue therapy depends on the drugs used in the first eradication attempt, since repeating the same antibiotic is not recommended. Systematic bacterial culture after a first H. pylori eradication failure does not seem to be required in clinical practice and this technique can be reserved for patients with a second failed attempt. There are several possibilities for empirical rescue therapy (without knowing the bacterial sensitivity). After failure of the combination of a proton pump inhibitor (PPI), amoxicillin and clarithromycin -the most widely used combination in Spain-, quadruple therapy (PPI-bismuth-tetracycline-metronidazole) has been the most widely used treatment. More recently, levofloxacin (together with amoxicillin and a PPI) is as effective as quadruple therapy, or more so, and has the advantage of being simpler and better tolerated. In addition, rescue therapy with levofloxacin is a promising third-line alternative after failure of two eradication therapies containing key antibiotics such as amoxicillin, clarithromycin, metronidazole and tetracycline. Finally, rifabutin-based therapies have achieved promising results and are even effective in patients with multiple failures or multiple antibiotic resistance.     

Helicobacter pylori:Management in 2013

Helicobacter pylori(H.pylori)is a prevalent,worldwide,chronic infection.Choice of treatment can be modified according to antibiotic-resistance rates of H.pylori.The ideal therapeutic regimen for H.pylori infection should achieve an eradication rate of≥80%.In some countries,triple therapy with a proton-pump inhibitor(PPI),clarithromycin,and amoxicillin or metronidazole is still the best option.Bismuth-containing quadruple therapy consisting of bismuth salts,tetracycline,metronidazole and PPI,may be the preferred option in countries with clarithromycin resistance>20%.Sequential therapy including a PPI and amoxicillin given for the first 5 d,followed by triple therapy including a PPI,clarithromycin,and nitroimidazole antimicrobial(all twice daily)for the remaining 5 d,can be another option for the first-line treatment of H.pylori.Recent data suggest that treatment with PPI,levofloxacin,and amoxicillin for 10 d is a good choice for second-line therapy.Concomitant therapy consisting of PPI,amoxicillin,clarithromycin and metronidazole is another option for second-line treatment.If second-line treatment also fails,it is recommended to culture H.pylori from biopsy specimens and perform antimicrobial susceptibility testing.Rescue treatment should be based on antimicrobial susceptibility.     

Comparison of three different second-line quadruple therapies including bismuth subcitrate in Turkish patients with non-ulcer dyspepsia who failed to eradicate Helicobacter pylori with a 14-day standard first-line therapy

Background and Aim: Many studies have reported poor results with standard first‐line treatment for Helicobacter pylori. Second‐line regimens that may overcome bacterial resistance can minimize side‐effects and optimize compliance. The aim of this study was to evaluate the efficacy of proton pump inhibitor (PPI) and bismuth subcitrate‐based quadruple therapy, after failure of a PPI plus clarithromycin and amoxicillin as first‐line therapy. Methods: Patients who failed to eradicate the infection after initial therapy were randomly separated into three groups. The first group received lansoprazole, bismuth subcitrate, metronidazole and amoxicillin (LBMA); in the second group metronidazole was replaced by tetracycline (LBTA); and the third group was given metronidazole and tetracycline in addition to same doses of lansoprazole and bismuth subcitrate (LBMT). Results: In the LBMA group, the eradication rate was 74.7% and was significantly related to sex, with no relationship to age. In the LBTA group the eradication rate was 81.5% with similar rates in males and females. No relation to sex or age was observed. In the LBMT group the eradication rate was 82.1% with no difference between women and men and it was not related to age, either. Eradication rates in study groups were similar (P > 0.05). Conclusion: A‐14‐day regimen of lansoprazole, bismuth subcitrate and antibiotic pairs, tetracycline–amoxicillin and tetracycline–metronidazole, is an effective quadruple therapy after one failed course of standard triple therapy. The evaluation of tolerability of and compliance with quadruple therapy needs further studies.     

Comparison of the efficacy of 1‐day high‐dose quadruple therapy versus 7‐day triple therapy for treatment of Helicobacter pylori infection

BACKGROUND: The proton pump inhibitor (PPI)‐based 7‐day triple therapy is the regimen with the highest cure rates for eradication of Helicobacter pylori infection and has been recommended as the first‐line regimen in the world. It had been reported that a 1‐day quadruple therapy could also successfully cure 95% of the H. pylori infected patients. OBJECTIVES: To observe the efficacy of 1‐day high‐dose quadruple therapy versus 7‐day triple therapy for treatment of H. pylori infection, and to observe side‐effects of the two different regimens. METHODS: This randomized, open, parallel‐controlled study was conducted at Renji Hospital between November 2004 to March 2005. A total of 80 consecutive patients with non‐ulcer dyspepsia, who were H. pylori positive proven by both rapid urease test and histology were included and randomly assigned to 1‐day quadruple therapy or 7‐day triple therapy. Thirty‐nine patients were administered with 1‐day high‐dose quadruple therapy including esomeprazole 40 mg b.i.d., colloidal bismuth subcitrate 440 mg q.i.d., amoxicillin 2 g q.i.d. and metronidazole (400 mg q.i.d.) for 1 day. Forty‐one patients received a standard 7‐day triple therapy consisting of esomeprazole 20 mg b.i.d., clarithromycin 500 mg b.i.d. and amoxicillin 1 g b.i.d. for 7 days. The eradication rates were evaluated by the ¹³C‐urea breath test at least 4 weeks after completion of a course treatment. RESULTS: Seventy‐seven patients completed the trial and three patients dropped out. The eradication rates in the 1‐day therapeutic group and the 7‐day therapeutic group were 39.5% (15/38) and 84.6% (33/39), respectively. There was a statistically significant difference between the two groups (P < 0.0001). Short‐lasting and self‐limiting side effects including thirst, a metallic taste, diarrhea and abdominal pain were reported in three patients (7.9%) in the 1‐day group and seven patients (18%) in the 7‐day group (P = 0.31). CONCLUSIONS: A 1‐day high‐dose quadruple therapy with amoxicillin, metronidazole, bismuth salt, and esomeprazole is not effective for eradication of H. pylori compared with the standard 7‐day triple therapy.     

10 Eradication of Helicobacter pylori

Although there are numerous publications reporting eradication results, the general picture is confused by the bewildering multiplicity of treatment schedules employed by the various workers. The over-riding need now is for large scale trials, and more especially for direct comparisons of different treatment regimens in the same populations of patients. Such data are entirely absent from the literature at present. Standardization of definitions and of methodology pertaining to diagnosis of eradication, recording of side effects, measurement of compliance and determination of recurrence or of reinfection, is badly needed. As the definition of eradication remains arbitrary, it is important to include genome fingerprinting techniques in the long-term follow-up for recurrence, so that the question of reinfection versus recrudescence can be examined (Bell et al, 1993b; Xia et al, 1994).Because of the wide differences in the agents used in H. pylori eradication therapies, proper double-blinding of treatment trials remains a difficult problem. This can be dealt with to some extent by ensuring that the interpretation of tests for H. pylori eradication is performed by personnel unaware of the clinical details.Review of the existing data on eradication of H. pylori indicates that clinically useful results can be achieved in some 70 to 95% of patients, on an intention to treat basis. Compliance, side effects and resistance to metronidazole remain the limiting factors. Efficacy, freedom from side effects, simplicity and low cost will determine the success of any regimen in the future. At present, it is not possible to make firm recommendations in favour of one regimen over another, but it seems reasonable to forecast that dual therapies consisting of a PPI and an antibiotic will receive much attention. Preparations consisting of an H₂RA associated with a bismuth compound, which are used together with an antibiotic are an interesting approach. Compliance should be as good as with a normal dual therapy and the eradication results look promising (Wyeth et al, 1994; Webb et al, 1994).The advantages of dual therapies that include a PPI lie in their simplicity, in not relying on imidazole for their anti-H. pylori effect but on the profound inhibition of acid output produced by the PPI. Thus PPI based dual therapy can probably evoke better compliance than the more complicated regimens.The use of PPIs has other advantages in addition to decreasing the MIC₉₀ of the antibiotic combined with it. This is because administration of a powerful inhibitor of gastric acid secretion, such as a PPI, will aid the rapid healing of an ulcer crater and will rapidly relieve the symptoms of peptic ulceration. Gastrin releasing peptide-stimulated acid secretion is raised in duodenal ulcer patients to approximately sixfold over control levels according to El-Omar et al (1993b), and although it returns to normal following the eradication of H. pylori, this process takes time to become effective (El-Omar et al, 1993a). Suppression of acid output provides an immediate therapeutic shield, while the decrease in inflammation and acid output secondary to H. pylori eradication can be established.The most widespread resistance to antibiotics exhibited by H. pylori is with respect to imidazoles. The prevalence of metronidazole resistance is widespread in the emergent countries (Glupczynski et al, 1990), but it is also appreciable in the West, especially in women, who may have been given metronidazole in the treatment of pelvic infections (Rautelin et al, 1992; Banatvala et al, 1994). Moreover, H. pylori becomes resistant to metronidazole very easily and often as a result of treatment which includes an imidazole compound (Malfertheiner, 1993; Banatvala et al, 1994). On the other hand, H. pylori resistance to macrolides is not widespread and does not develop easily during their administration. It is difficult to forecast which antibiotic will be the most widely used agent in combination with a PPI. Amoxycillin seems quite effective when combined with a PPI administered twice daily, while clarithromycin leads the macrolides in its in vitro anti-H. pylori activity.Bismuth-based triple regimens have the advantage of familiarity. Ensuring compliance is the duty of the physician initiating the treatment. The incidence of eradication with these regimens differs in different centres (Logan et al, 1991a; Bell et al, 1993a) and the reasons for these discrepancies need to be investigated.One week, low dose triple therapy with omeprazole, clarithromycin and tinidazole or metronidazole appears highly effective, with few side effects and good compliance (Bazzoli et al, 1994; Jaup and Norrby, 1994; Moayyedi and Axon, 1994; Labenz et al, 1995). However, data is not available on the pretreatment sensitivity to nitroimidazoles of H. pylori from the patients studied, or of the development of resistant strains during treatment. Further studies are needed to confirm these encouraging results in different populations and with pre-treatment H. pylori sensitivities.The ideal regimen for the eradication of H. pylori does not exist at present. Moreover, note has to be taken of epidemiology of the bacterium in different parts of the world. Eradication strategies may be confounded in the emergent countries, where prevalence and resistance patterns to antibiotics are so different from the first world.     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> and gastroesophageal reflux disease

Opinion statement Since the rediscovery of Helicobacter pylori two decades ago, it has become increasingly clear that the true relationships between this organism and diseases of the upper gastrointestinal tract are highly complex. H. pylori colonization is a strong risk factor for peptic ulceration and distal gastric cancer; however, gastritis has no adverse consequences for most hosts, and the prevalence of H. pylori is inversely related to gastroesophageal reflux disease (GERD) and its sequelae, which include Barrett’s esophagus and esophageal adenocarcinoma. One clinical implication stemming from these data is that H. pylori eradication may not be appropriate in certain human populations due to potential beneficial effects conferred by persistent gastric inflammation. However, the majority of published intervention trials indicate that H. pylori treatment neither leads to the development of clinically significant de novo esophagitis nor exacerbates existing reflux disease. Superimposed upon these observations are reports that long-term acid suppression induced by proton-pump inhibitors (PPIs) in conjunction with H. pylori colonization may enhance the development of atrophic gastritis, a well-recognized histologic step in the progression to intestinal-type gastric cancer. Therefore, current evidence-based recommendations regarding management of H. pylori-positive individuals with GERD include the following. H. pylori should not be treated with the intent to either improve reflux symptoms or prevent the development of reflux complications. However, if patients are to receive long-term acid suppressive therapy, they should be tested for H. pylori and treated if positive, due to the potential for PPIs to accelerate atrophy within H. pylori-infected mucosa. Optimal first-line regimens in this country consist of a PPI in combination with clarithromycin and either amoxicillin or metronidazole (triple therapy) for at least 7, but preferably 10, days. Because the most effective second-line regimens contain metronidazole, it is advisable to use amoxicillin instead of metronidazole as first-line therapy in order to optimize results should subsequent therapy be required. If first-line regimens fail to eliminate H. pylori, patients should receive quadruple therapy consisting of a PPI, bismuth subsalicylate, metronidazole, and tetracycline for 14 days. Due to the availability and accuracy of noninvasive diagnostic tests for H. pylori, it is recommended that successful cure be confirmed after intervention.     

The influence of pretreatment with PPI on Helicobacter pylori eradication: A systematic review and meta-analysis

Background:In this meta-analysis, we aimed to comprehensively investigate the impact of pretreatment with proton pump inhibitor (PPI) on Helicobacter pylori (H. pylori) eradication and provide novel inspiration to clinical practice.Methods:Relevant studies were selected through PubMed, Embase, and Cochrane Library from inception to March 2021. Two reviewers performed the selection independently. The primary outcome of the meta-analysis was the eradication rate. A modified Jadad scale was used to evaluate literature quality quantitatively.Results:Ten studies were included in this research. The results showed no significant difference between PPI pretreatment and standard treatment on eradication of H. pylori [relative risk (RR): 1.17, 95% confidence interval (95% CI): 0.0.73–1.88]. There was no significant difference between the PPI pretreatment group and the standard therapy group for conventional triple therapy, PPI and amoxicillin and clarithromycin (RR: 1.29, 95% CI: 0.60–2.77). Similar results were obtained in the therapy strategy of PPI and amoxicillin and metronidazole (RR: 3.01, 95% CI: 0.62–14.74). Interestingly, for the therapy regimen of PPI and clarithromycin and metronidazole, PPI pretreatment indicated superiority on H. pylori eradication rate (RR: 0.48, 95% CI: 0.23–0.97, P < .05).Conclusion:PPI pretreatment did not affect the H. pylori eradication rates, regardless of the various types of bacteriostatic antibiotic, except the therapy regimen of PPI and clarithromycin and metronidazole.     

Probiotics as an adjuvant treatment in Helicobacter pylori eradication therapy

Over 80% of individuals infected with Helicobacter pylori (H. pylori) are asymptomatic. Increased resistance to antibiotics and decreased compliance to the therapeutic regimens have led to the failure of eradication therapy. Probiotics, with direct and indirect inhibitory effects on H. pylori in both animal models and clinical trials, have recently been used as a supplementary treatment in H. pylori eradication therapy. Probiotics have been considered useful because of the improvements in H. pylori eradication rates and therapy‐related side effects although treatment outcomes using probiotics are controversial due to the heterogeneity of species, strains, doses and therapeutic duration of probiotics. Thus, despite the positive role of probiotics, several factors need to be further considered during their applications. Moreover, adverse events of probiotic use need to be noted. Further investigations into the safety of adjuvant probiotics to H. pylori eradication therapy are required.     

Ten-day sequential therapy is more effective than proton pump inhibitor-based therapy in Korea: a prospective, randomized study

Background and Aims: The eradication rate of proton pump inhibitor (PPI)‐based triple therapy for Helicobacter pylori (H. pylori) infection has decreased, mainly due to increasing antibiotic resistance, especially against clarithromycin. It has been reported that a 10‐day sequential strategy can produce good outcomes. The aim of this prospective study was to assess the efficacy of sequential therapy as the first‐line treatment for the eradication of H. pylori in Korea. Methods: A total of 116 patients with proven H. pylori infection received 10‐day sequential therapy (20 mg rabeprazole and 1 g amoxicillin, twice daily for the first 5 days, followed by 20 mg rabeprazole, 500 mg clarithromycin, and 500 mg metronidazole, twice daily for the remaining 5 days); 130 patients received 7‐day triple therapy (20 mg rabeprazole, 500 mg clarithromycin, and 1 g amoxicillin, twice daily for 7 days). Eradication was evaluated by the ¹³C‐urea breath test, 4 weeks after the completion of treatment. Compliance and adverse events were assessed. Results: The eradication rates of 10‐day sequential therapy and PPI‐based triple therapy were 79.3% (92/116) and 63% (82/130) by intention‐to‐treat analysis, respectively (P = 0.005), and 81.9% (91/111) and 64.5% (82/127) by per protocol analysis, respectively (P = 0.003). Mild adverse events occurred in both therapy groups (27.5% vs 23.8%), but both treatments were well tolerated. Conclusion: The eradication rate of the 10‐day sequential therapy regimen was significantly higher than that of PPI‐based triple therapy in the Korean population. Ten‐day sequential therapy might be effective as a first‐line treatment for H. pylori infection in Korea.