A Randomized Controlled Trial: Efficacy and Safety of Azithromycin,Ofloxacin, Bismuth,and Omeprazole Compared With Amoxicillin,Clarithromycin, Bismuth,and Omeprazole as Second‐Line Therapy in Patients With Helicobacter pylori Infection

Background: Helicobacter pylori infection of the stomach is widespread among human populations and is considered to play a major role in the pathogenesis of various diseases such as peptic ulcer, adenocarcinoma, and mucosa associated lymphoid tissue (MALT) lymphoma of the stomach. To increase H. pylori eradication rate without increasing bacterial resistance, various regimens have been recommended. Commonly the association of at least two antibiotics with a proton‐pump inhibitor is used. The treatment regimens for second‐line therapy, suggested in studies from the western world may not be ideal in Iran. Aim: In this study, we evaluated the safety and efficacy of a new quadruple therapy regimen and compared it with the standard second‐line treatment for H. pylori eradication. Methods: We selected 220 H. pylori positive patients, with a clear indication of eradication therapy, who did not respond to a 2 weeks treatment with metronidazole, amoxicillin, omeprazole, and bismuth. They were randomized into two groups. Group A (n = 110) were treated with azithromycin, ofloxacin, bismuth, and omeprazole and group B (n = 110) with amoxicillin, clarithromycin, bismuth, and omeprazole for 2 weeks. Four weeks after the end of treatment, urea breath test was performed for all subjects to confirm eradication. Results: In intention‐to‐treat analysis, the rate of H. pylori eradication in groups A and B was 77.3% (85/110) and 64.5% (71/110) respectively (p = .027). In per‐protocol analysis, the rate of H. pylori eradication in groups A and B was 86.7 and 74.7%, respectively (p = .026). The incidence of poor compliance was lower, although not significantly so, in group A than group B (3.5 vs 4.3%). No major adverse events occurred in both groups. Conclusion: Two weeks of treatment with ofloxacin, azithromycin, omeprazole, and bismuth is an effective and safe regimen for H. pylori eradication as second‐line therapy.     

Quadruple therapy with medications containing either rufloxacin or furazolidone as a rescue regimen in the treatment of Helicobacter pylori-infected dyspepsia patients: a randomized pilot study

Background: The eradication rates of first‐line treatment for Helicobacter pylori infection are not satisfactory. Various regimens including quadruple therapies have been recommended as rescue therapies after the first H. pylori eradication attempt failed. Aims: To compare the efficacy and safety between quadruple therapies with medications containing either rufloxacin or levofloxacin in the Chinese nonulcer dyspepsia patients infected with H. pylori. Methods: One hundred and thirty‐eight patients after an unsuccessful 10‐day standard triple therapy were enrolled in this study. They were randomized to receive a 14‐day quadruple therapy with pantoprazole, bismuth citrate, and furazolidone in combination with either rufloxacin (Group Ruf, n = 70) or levofloxacin (Group Lev, n = 68). The H. pylori eradication was evaluated by ¹³C‐urea breath test 4 and 12 weeks after therapy was completed. Results: One hundred and twenty‐seven patients (65 in Group Ruf and 62 in Group Lev) completed the study. The H. pylori eradication rates in Group Ruf were 81.4% for intention‐to‐treat (ITT) analysis and 87.7% for per‐protocol (PP) analysis. The rates were statistically significantly higher than those in Group Lev (66.2% and 72.6%) (p < 0.05). There were no severe adverse effects found in these two groups. Conclusions: Fourteen‐day quadruple therapy with a combination of proton‐pump inhibitor, bismuth citrate, furazolidone, and rufloxacin is considered an effective and safe rescue therapy for H. pylori eradication after failure of standard triple treatment.     

Helicobacter pylori infection: sequential therapy followed by levofloxacin-containing triple therapy provides a good cumulative eradication rate

Background: In the eradication of H. pylori infection, even today, the main international guidelines recommend the triple therapy as first‐line regimen, although its effectiveness is clearly decreasing. As second‐line treatment, the bismuth‐containing quadruple therapy is the most used regimen, although several other therapies are studied. The Italian guidelines recommend, alternatively, sequential therapy or triple therapy as first‐line treatment and levofloxacin‐containing triple therapy as second‐line regimen. We wanted to assess the overall eradication rate of Helicobacter pylori infection in two therapeutic rounds following the Italian guidelines in clinical practice. Materials and Methods: We treated 231 consecutive Helicobacter pylori‐positive patients by sequential therapy and we verified the eradication 8–10 weeks after treatment by stool antigen test. Patients positive for stool antigen test received levofloxacin‐containing triple therapy, as second‐line therapy, according to Italian Guidelines and they were again submitted to the fecal test 8–10 weeks after the end of treatment. Results: In the first‐line regimen, we obtained an eradication rate of 92.6%, in the second‐line of 75.0% and as cumulative result we achieved a 97.8% of eradication, in per‐protocol analysis. Conclusions: Sequential therapy as first‐line and levofloxacin‐containing triple therapy as second‐line represent a good combination to eradicate Helicobacter pylori infection in only two rounds.     

High Efficacy of 14‐Day Triple Therapy‐Based,Bismuth‐Containing Quadruple Therapy for Initial Helicobacter pylori Eradication

Background: The success rate of currently recommended 7‐day triple therapy with a PPI plus amoxicillin and clarithromycin has fallen into the unacceptable range. It is urgent to look for a new strategy to treat the infection of Helicobacter pylori. Aims: To observe the efficacy of triple therapy‐based, bismuth‐containing quadruple therapy for H. pylori treatment. Methods: A total of 160 patients with functional dyspepsia who were Hp+ were randomly assigned into two groups. Regimen: Omeprazole 20 mg, Amoxicillin 1.0 g, Clarithromycin 500 mg and Bismuth Potassium Citrate 220 mg, twice a day. Eighty patients received 7‐day quadruple therapy and 80 patients received the same therapy for 14 days. Six weeks after treatment, H. pylori eradication was assessed by ¹³C‐urea breath test. Minimal inhibitory concentrations of metronidazole, clarithromycin and amoxicillin of clinical isolates were determined by the twofold agar dilution method. Results: Fourteen‐day therapy led to a significant increase of H. pylori eradication success when compared to 7‐day therapy in the intention‐to‐treat analysis (93.7 vs 80.0%; p = .01), and the per‐protocol analysis (97.4 vs 82.0%; p = .0016). The H. pylori resistance rates to metronidazole, clarithromycin and amoxicillin were 42.1, 18.0 and 0%. Fourteen‐day therapy was significantly more effective in patients with clarithromycin‐resistant strains. Incidences of adverse events were comparable. Conclusions: Addition bismuth and prolonging treatment duration can overcome H. pylori resistance to clarithromycin and decrease the bacterial load. Fourteen‐day triple therapy‐based, bismuth‐containing quadruple therapy achieved ITT success rate 93% and could be recommended as the first line eradication regimen.     

Review: Clinical Management of Helicobacter pylori Infection in China

Helicobacter pylori (H. pylori) infection has been associated with gastric disorders. The situation of H. pylori infection in China—where a high prevalence of H. pylori infection, a high incidence of gastric cancer, and widespread resistance to clarithromycin, metronidazole, and levofloxacin exist—is quite different from that in Western countries. In order for Chinese clinicians to better manage H. pylori infection, a Chinese Study Group on H. pylori published four consensus reports regarding the management of H. pylori infection in China between 1999 and 2012. The eradication rate with standard triple therapy was <80% in most areas of China. Bismuth is available in China, and bismuth‐containing quadruple therapy has been shown to produce a high eradication rate; thus, bismuth quadruple therapy could be recommended both as an initial and as a rescue therapy in China. There is no advantage of sequential therapy over triple therapy in Chinese patients, but the efficacy of concomitant therapy must be studied further. This review introduces the epidemiology, diagnosis, indicators, and therapies for the eradication of H. pylori in China in recent years.     

A modified bismuth-containing quadruple therapy including a short course of furazolidone for Helicobacter pylori eradication after sequential therapy failure

Background: Helicobacter pylori eradication has still remained a challenge, especially in case of failure to novel treatments. Therefore, we designed a study to evaluate the effects of a modified bismuth‐containing quadruple therapy including a short course of furazolidone on a group of patients whose sequential therapy had been unsuccessful. Materials and Methods: Thirty‐six H. pylori‐positive patients who had previously failed a clarithromycin‐containing sequential therapy enrolled the study. They received pantoprazole (40 mg‐bid), amoxicillin (1 g‐bid), and bismuth subcitrate (240 mg‐bid) for 2 weeks and furazolidone (200 mg‐bid) just during the first week. Eight weeks after treatment, H. pylori eradication was reassessed using C14‐urea breath test. Results: Thirty five patients completed the study. H. pylori eradication rates were 80.6% (95% CI = 67.6–93.5) and 82.9% (95% CI = 70.6–95.2) according to intention‐to‐treat and per‐protocol analyses, respectively. All patients had excellent compliance to treatment, and no one interrupted therapy owing to adverse effects. Conclusion: Regarding the eradication rate (>80%), low price, and very low adverse effects, a 2‐week bismuth‐containing quadruple regimen including a short course of furazolidone can be an encouraging regimen for second‐line H. pylori eradication in case of sequential therapy failure. Possibly, it can be improved by alterations in dose, dosing intervals, and/or duration.     

Furazolidone‐containing triple and quadruple eradication therapy for initial treatment for Helicobacter pylori infection: A multicenter randomized controlled trial in China

Background

The efficacy of Helicobacter pylori (H. pylori) eradication has steadily declined, primarily because of antibiotic resistance. This study aimed to evaluate the efficacy and safety of furazolidone eradication therapies as initial treatments for H. pylori infection.

Methods

A national, multicenter, open‐label, randomized controlled trial was performed at 16 sites across 13 provinces in China to evaluate the efficacy and safety of furazolidone‐containing therapies for H. pylori infection. Treatment naïve patients were randomly assigned to: esomeprazole 20 mg, bismuth 220 mg, amoxicillin 1000 mg, and furazolidone 100 mg twice daily for 10 and 7 days (FAB 10 and FAB 7; the same therapy without bismuth (FA 10 and FA 7). The primary and secondary outcomes were the eradication rate and regimen safety, respectively. Treatment success was assessed by the ¹³C urea breath test at least 4 weeks after treatment completion.

Results

Overall, according to intention‐to‐treat (ITT) analysis, the eradication rates for FAB 10 and FAB 7 were 86.6% (95% confidence interval [CI], 79.9%‐93.2%) and 83.6% (95% CI, 76.3%‐90.9%) and for FA 10 and FA 7 were 82.4% (95% CI, 74.9%‐89.8%) and 77.6% (95% CI, 69.4%‐85.8%), respectively. According to per‐protocol analysis, the overall eradication rates for FAB 10 and FAB 7 were 94.7% (95% CI, 90.3%‐99.1%) and 90.8% (95% CI, 85.1%‐96.5%) and for FA 10 and FA 7 were 90.6% (95% CI, 84.9%‐96.3%) and 85.1% (95% CI, 78.2%‐92.1%), respectively. The overall prevalence of side effects was 8.1%.

Conclusions

Furazolidone‐containing therapies, particularly the tested 10‐day quadruple therapy, exhibited satisfactory efficacy and safety. This 10‐day quadruple therapy represents a promising initial treatment strategy for Chinese patients.     

Review – Treatment of Helicobacter pylori infection 2020

This review summarizes important studies regarding Helicobacter pylori therapy published from April 2019 to April 2020. The main themes that emerge involve studies assessing antibiotic resistance, and there is also growing momentum behind the utility of vonoprazan as an alternative to proton pump inhibitor (PPI) therapy and also bismuth‐based regimens as a first‐line regimen. Antibiotic resistance is rising wherever it is being assessed, and clarithromycin resistance in particular has reached a point where it may no longer be a viable therapy without previous testing in many regions of the world. The evidence for the efficacy of a bismuth‐based quadruple therapy as a first‐line therapy is now very clearly established, and there is substantial evidence that it is the best performing first‐line therapy. The utility of vonoprazan as an alternative to PPI therapy, especially in resistant and difficult‐to‐treat groups, has also been considered in great detail this year, and it may offer an opportunity in the near future to reduce the problem of antibiotic resistance.     

Effectiveness and safety of repeated quadruple therapy in Helicobacter pylori infection after failure of second-line quadruple therapy: repeated quadruple therapy as a third-line therapy

Backgrounds: Quadruple therapy using a proton‐pump inhibitor, bismuth, metronidazole, and tetracycline is a standard second‐line therapy for Helicobacter pylori infection, achieving an eradication rate of about 80% in Korea. A standard third‐line therapy is not currently established, although various protocols have been proposed. We performed this study to evaluate the effectiveness of a retrial with quadruple therapy before starting a third‐line treatment with new drugs. Materials and Methods: In 80 of 746 patients treated with a second‐line quadruple therapy at the Korea University Ansan Hospital between January 2002 and September 2010, treatment for H. pylori had failed, and 45 of these patients were eligible for this study. Eradication of H. pylori was assessed by repeated endoscopy or by the ¹³C‐urea breath test at least 4 weeks after therapy. The patients with treatment failure were treated again with quadruple regimen for 2 weeks and reevaluated for treatment effectiveness and safety. Results: The eradication rate with second‐line quadruple therapy was 86.9%. Of the 80 patients who failed treatment for H. pylori with the initial second‐line quadruple therapy, 64 patients were treated again with the same regimen. Of the 45 retreated patients in this study, three patients were lost to follow‐up and two complied poorly with medication. The eradication rate in the 40 patients retreated was 75.0% at per‐protocol analysis. Seventeen patients experienced mild adverse events. Conclusions: A retrial of quadruple therapy before use of a third‐line therapy may be safe and effective for patients who fail to respond to second‐line quadruple therapy.     

Anti‐Helicobacter pylori therapy in localized gastric mucosa‐associated lymphoid tissue lymphoma: A prospective,nationwide, multicenter study in Japan

Background

Helicobacter pylori eradication therapy was approved in Japan for the first‐line, standard treatment of H. pylori‐positive gastric mucosa‐associated lymphoid tissue (MALT) lymphoma. Although several retrospective studies or small‐scale single‐center studies have been reported, a prospective, large‐scale, nationwide, multicenter study has not been reported from Japan.

Materials and Methods

We conducted a prospective, nationwide, multicenter study to evaluate the clinical efficacy of rabeprazole‐based triple H. pylori eradication therapy for patients with localized gastric MALT lymphoma in practice‐based clinical trial. A total of 108 H. pylori‐positive patients with stage I/II₁ gastric MALT lymphoma underwent H. pylori eradication therapy. The primary endpoints were complete remission (CR) rate and the rate of transfer to secondary treatment. The secondary endpoints were CR maintenance duration and overall survival (OS).

Results

CR of lymphoma was achieved in 84 of 97 patients (86.6%), during the period 2.0‐44.7 months (median, 5.3 months) after starting H. pylori eradication treatment. CR was maintained in 77 of 81 patients (95.1%) for 0.4‐53.2 months (median, 33.1 months). Secondary treatments (radiotherapy, rituximab, or gastrectomy) for gastric MALT lymphoma were needed in 10 of the 97 patients (10.31%). During follow‐up, OS rate was 96.9% (94/97) and the causes of 3 deaths were not related to lymphoma.

Conclusions

Rabeprazole‐based H. pylori eradication therapy demonstrated a high CR rate, long CR maintenance, and a good OS for patients with localized gastric MALT lymphoma in this prospective, practice‐based, multicenter study.     

Review: Epidemiology of Helicobacter pylori infection

This review summarizes recent publications on the epidemiology of Helicobacter pylori. Two major systemic analyses, from Malaysia and Ethiopia, were published. The Brazilian Consensus Conference has stated that H pylori infection is an infectious disease with an indication for antimicrobial therapy. A continuous decrease in H pylori prevalence was reported from many regions worldwide, including Korea, China, Iran, and Austria. A cross‐sectional H pylori prevalence study conducted in the United Arab Emirates found 41% prevalence in a group of healthy children and adults. Several studies from Asia addressed H pylori prevalence in adults undergoing regular checkup. The largest of such studies, performed in Korea, involved 24 471 subjects and reported 41.5% seroprevalence. A relatively smaller study from East China on 3252 subjects reported 27.5% prevalence. In contrast, a study from Spain reported 87.2% seroprevalence. A report on the association between smoking and H pylori seropositivity was published on behalf of the Stomach Cancer Pooling (StoP) Project—a consortium of epidemiological studies of gastric cancer. Also, other potential risk factors, including occupational risk factors, water supply, and food were analyzed. Gastroesophageal reflux and sexual partners has been associated with a higher risk for H pylori acquisition, and gut microbiota was suggested to play a role in intrafamilial transmission of H pylori. Finally, in a few studies (from Mexico and Japan), the catalytic model for predicting the potential risk of acquiring H pylori infection in the future was used. As anticipated, a further decline in H pylori‐related disease was demonstrated by applying the modeling.     

Moxifloxacin-containing triple therapy versus bismuth-containing quadruple therapy for second-line treatment of Helicobacter pylori infection: a meta-analysis

Background: Moxifloxacin‐containing triple therapy has been suggested as an alternative second‐line therapy for Helicobacter pylori infection. Aims: To systematically review the efficacy and tolerance of moxifloxacin‐containing triple therapy in second‐line H. pylori eradication, and to conduct a meta‐analysis of studies comparing this regimen with bismuth‐containing quadruple therapy. Materials and Methods: Electronic databases including Medline, Embase, Cochrane controlled trials register, Web of Science, PubMed, Chinese Biomedical Literature Database (updated to December 2010), and manual searches were conducted. A meta‐analysis of all randomized controlled trials (RCTs) comparing moxifloxacin‐containing triple therapy to bismuth‐containing quadruple therapy in the second‐line treatment of H. pylori infection was performed. Results: Seven RCTs including 787 patients were assessed. The meta‐analysis showed that the eradication rate in the moxifloxacin group was significantly higher than that in the quadruple therapy group (74.9 vs 61.4%, OR 1.89, 95% CI: 1.38–2.58, p < .0001); besides, the rates of side effects and discontinuing therapy because of side effects in the moxifloxacin group were significantly lower than those in the quadruple therapy group (side effects: 10.1 vs 27.8%, OR 0.27, 95% CI: 0.18–0.41, p < .00001; discontinuing therapy because of side effects: 1.4 vs 8.2%, OR 0.18, 95% CI: 0.08–0.40, p < .0001). These results were constant in the sensitivity analyses. Conclusion: Moxifloxacin‐containing triple regimen is more effective and better tolerated than the bismuth‐containing quadruple therapy in the second‐line treatment of H. pylori infection.     

Review ‐ Helicobacter pylori and non‐malignant upper gastro‐intestinal diseases

This review takes into account recent publications focusing on the relationship between Helicobacter pylori infection and non‐malignant diseases of the upper gastro‐intestinal tract. The authors have summarized current knowledge on associations between the H pylori infection and non‐malignant upper GI conditions including gastroesophageal reflux disease (GERD), Barrett's esophagus, eosinophilic esophagitis (EOE), peptic ulcer disease (PUD), H pylori gastritis, celiac disease and functional dyspepsia. In the field of GERD, current data focusing on different locations of H pylori infection detect significant differences between antrum‐ and corpus predominant gastritis explainable by different changes in acid secretion in different gastric niches. High volume studies from Sweden and Brazil underline the safety of H pylori eradication concerning the risk of Barret's esophagus or adenocarcinoma. The relationship betweenH pylori infection and EOE remains uncertain, but current data supports the concept of expected positive and protective effects of H pylori exposure reducing the risk of EOE. Analyzing biomarkers might be helpful to identify subjects under risk for the development of precancerous lesions after H pylori infection, where microRNAs, IL‐9 and IL‐4, and also Tc17/9 and Th17/9 and microbiota profiles showed promising results to identify subgroups under risk.     

Review: Helicobacter pylori in pediatrics

Despite a decrease in the prevalence of Helicobacter pylori infection, it still poses a significant health burden worldwide. This review summarizes important pediatric studies on H pylori published from April 2018 to March 2019. Epidemiologic studies have reported different prevalences in different parts of the world and have mainly confirmed traditional risk factors. Several studies on pathophysiology attempted to identify risk markers in childhood for gastric cancer development later in life. One of the most interesting studies evaluated the relationship between eosinophilic esophagitis and H pylori infection; however, an inverse relationship was not confirmed. The high resistance of H pylori and, consequently, low eradication rates, is still a major concern and susceptibility testing before treatment has again been highlighted. Potassium‐competitive acid blockers are promising new acid‐suppressant drugs but their role in H pylori eradication schemes is still to be determined.     

High eradication rates of Helicobacter pylori infection following sequential therapy: the Israeli experience treating naïve patients

Background: Helicobacter pylori eradication rates following triple therapy are decreasing. Cure rates as low as 57%, mainly to claritromycin resistance, have been reported in Israel. Studies performed in Italy have shown eradication rates of 93%, following sequential therapy. Our aim was to evaluate the effect of sequential therapy on eradication rates of H. pylori in naïve Israeli patients. Material and Methods: Consecutive patients referred for esophagogastroduodenoscopy with a positive rapid urease test and positive ¹³C urea breath test were included. Patients received omeprazole 20 mg bid and amoxicillin 1 g bid for 5 days followed by omeprazole 20 mg bid, clarithromycin 500 mg bid and tinidazole 500 mg bid for the subsequent 5 days. A second ¹³C urea breath test was performed at least 4 weeks after completion of therapy. Patients were asked to avoid antibiotics, bismuth compounds or proton pump inhibitor until after the second ¹³C urea breath test. Adverse effects were documented by a questionnaire. Results: One hundred and twenty‐four patients (mean age 56.1 ± 12.5 years, 55.6% women) were included; 120/124 (96.8%) completed treatment and performed the second ¹³C urea breath test. Two patients (1.6%) were lost to follow‐up; 2 (1.6%) were noncompliant with study regulations. One hundred and fifteen patients achieved eradication of H. pylori. The eradication rate was 95.8% by per protocol analysis and 92.7% by intention to treat analysis. Conclusion: The sequential regimen attained significantly higher eradication rates in naïve patients than usually reported for conventional triple therapy. Sequential therapy may be an alternative first‐line therapy in eradicating H. pylori in Israel.     

Review: Helicobacter pylori infection in children

Helicobacter pylori infection in children and adolescents differs in comparison to adults with respect to epidemiology, host responses, and disease manifestations. Furthermore, treatment options are limited in this population and antibiotic resistance rates continue to increase. Therefore, ongoing research is vital to understand disease pathogenesis and provide optimal management of children with infection. This review summarizes relevant publications from April 2019 to March 2020. Similar to adults, recent studies show a decreasing prevalence of infection in the pediatric population. Studies of pathogenesis investigated serum immune responses and the potential inverse association of infection and allergy. Several studies investigated the effect of H pylori and related inflammation on the gut microbiome. The recommendation of endoscopy‐based testing to identify the cause of symptoms and not just H pylori, reserving noninvasive UBT or stool antigen tests for post‐eradication follow‐up, was supported by the current literature.     

Comparison of lafutidine and rabeprazole in 7-day second-line amoxicillin- and metronidazole-containing triple therapy for Helicobacter pylori: a pilot study

Background: Lafutidine is an H2‐receptor antagonist with gastroprotective action through capsaicin‐sensitive afferent neurons and relatively inexpensive compare to proton‐pump inhibitors (PPIs). A 7‐day course of PPIs–amoxicillin–metronidazole is recommended as standard second‐line Helicobacter pylori therapy and is covered by national health insurance in Japan. The aim of this study was to determine the efficacy and safety of second‐line eradication using the H2‐receptor antagonist lafutidine as a substitute for a PPI. Materials and Methods: Fifty‐two patients who failed in first‐line eradication using PPI–amoxicillin–clarithromycin were randomly assigned to a 7‐day course of rabeprazole at 10 mg b.i.d., amoxicillin at 750 mg b.i.d., and metronidazole at 250 mg b.i.d. (RPZ‐AM) or a 7‐day course of lafutidine at 10 mg t.i.d., amoxicillin at 750 mg b.i.d., and metronidazole at 250 mg b.i.d. (LFT‐AM) as second‐line therapy. Eradication was assessed by the ¹³C urea breath test. A drug susceptibility test was performed before the second‐line therapy. Results: Prior to second‐line H. pylori eradication, the rate of resistance to clarithromycin was 86.5% and the rate of resistance to metronidazole was 3.8%. The eradication rates for both LFT‐AM and RPZ‐AM groups were 96% (95%CI = 88.6–100%). There were no severe adverse events in either group. Conclusions: Lafutidine plus metronidazole–amoxicillin as second‐line therapy provided a high eradication rate and safe treatment similar to a PPI‐based regimen. Lafutidine‐based eradication therapy is therefore considered to be a promising alternative and is also expected to reduce health care costs in H. pylori eradication.     

Randomized comparison of two non-bismuth-containing second-line rescue therapies for Helicobacter pylori

Background: Classical second‐line anti‐Helicobacter pylori includes proton‐pump inhibitor, tetracycline, metronidazole, and bismuth salts, but alternative therapies are required owing to the restricted availability of the latter. Levofloxacin‐containing triple therapy is recommended but is expensive. Besides, quinolone resistance in an endemic tuberculosis infection area like Taiwan is concerned. The low in vitro antibiotic resistance to amoxicillin and tetracycline in Taiwanese H. pylori strains implies that in vivo esomeprazole/amoxicillin/tetracycline (EAT) second‐line rescue therapy may be effective. This study compared the efficacy of esomeprazole/amoxicillin/levofloxacin (EAL) and EAT second‐line eradication therapies and determines the clinical factors influencing the efficacy of salvage regimens. Materials and methods: One hundred and twenty‐eight patients who failed H. pylori eradication using the standard triple therapy for 7 days are randomly assigned to either EAL group (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, and levofloxacin 500 mg once daily) for 7 days or EAT group (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, tetracycline 500 mg four times daily) for 14 days. Follow‐up endoscopy or urea breath test was performed 8 weeks later to assess treatment response. Results: The eradication rates of EAL and EAT groups were 78.1 versus 75.0%, p = .676 (in intention‐to‐treat analysis) and 80.3 versus 80%, p = .0964 (per‐protocol analysis). Both groups exhibited similar drug compliance (95.3 vs 96.9%, p = .952) but more adverse events in the EAT group (6.3 vs 12.5%, p = .225). Conclusions: Despite low in vitro drug resistances to amoxicillin and tetracycline, the efficacy of 14‐day EAT regimens attained an unacceptable report card of 75% eradication rates in intention‐to‐treat analysis and was not even superior to the 7‐day EAL regimen. Drug–drug interaction between combined antibiotics should be considered other than in vivo drug resistances.     

Clarithromycin–Amoxycillin‐Containing Triple Therapy: A Valid Empirical First‐Line Treatment for Helicobacter pylori Eradication in Hong Kong?

Background: Recent studies have suggested the eradication rate for Helicobacter pylori infection with standard amoxycillin–clarithromycin‐containing triple therapy as first‐line treatment have fallen below 80%. Levofloxacin‐containing triple therapy was proposed as an alternative. The aim of this study is to compare the efficacy and tolerability of the standard 7‐day clarithromycin‐containing triple therapy against the 7‐day levofloxacin‐containing triple therapy, and to assess whether the classical triple therapy is still valid as empirical first‐line treatment for H. pylori infection in Hong Kong. Methods: Three hundred consecutive H. pylori‐positive patients were randomized to receive either 1 week of EAL (esomeprazole 20 mg b.d., amoxycillin 1 g b.d., and levofloxacin 500 mg daily) or EAC (esomeprazole 20 mg b.d., amoxycillin 1 g b.d., and clarithromycin 500 mg b.d.). H. pylori status was rechecked by ¹³C‐urea breath test 6 weeks after treatment. Patients who failed either of the first‐line eradication therapy were invited to undergo H. pylori susceptibility testing. Results: H. pylori eradication was achieved in 128 of 150 (85.3%) patients in EAL and 139 of 150 (92.7%) patients in EAC groups, respectively (p = .043), for both intention‐to‐treat and per‐protocol analysis. More patients in the clarithromycin‐ than the levofloxacin‐containing therapy group developed side effects from the medication (21.3% vs 13.3%, p = .060). Nine patients (six from the EAL group and three from the EAC group) who failed their corresponding eradication therapy returned for susceptibility testing. All nine isolates were highly resistant to levofloxacin (minimum inhibitory concentration or MIC > 32 μg/mL), whereas only two of the six isolates from the EAL group were resistant to clarithromycin (MIC > 0.5 μg/mL). Conclusions: The standard 7‐day clarithromycin‐containing triple therapy is still valid as the most effective empirical first‐line eradication therapy for H. pylori infection in Hong Kong, as prevalence of primary resistance of H. pylori to amoxycillin and clarithromycin remains low. Patients who failed their empirical first‐line eradication therapy should undergo H. pylori susceptibility testing to guide further treatment.     

Impact factors that modulate gastric cancer risk in Helicobacter pylori‐infected rodent models

Gastric cancer causes a large social and economic burden to humans. Helicobacter pylori (H pylori) infection is a major risk factor for distal gastric cancer. Detailed elucidation of H pylori pathogenesis is significant for the prevention and treatment of gastric cancer. Animal models of H pylori‐induced gastric cancer have provided an invaluable resource to help elucidate the mechanisms of H pylori‐induced carcinogenesis as well as the interaction between host and the bacterium. Rodent models are commonly used to study H pylori infection because H pylori‐induced pathological processes in the stomachs of rodents are similar to those in the stomachs of humans. The risk of gastric cancer in H pylori‐infected animal models is greatly dependent on host factors, bacterial determinants, environmental factors, and microbiota. However, the related mechanisms and the effects of the interactions among these impact factors on gastric carcinogenesis remain unclear. In this review, we summarize the impact factors mediating gastric cancer risk when establishing H pylori‐infected animal models. Clarifying these factors and their potential interactions will provide insights to construct animal models of gastric cancer and investigate the in‐depth mechanisms of H pylori pathogenesis, which might contribute to the management of H pylori‐associated gastric diseases.