• aging
• geriatric gastroenterology
• helicobacter pylori
• immunosenescence
• probiotic therapy

• Humans
• Helicobacter Infections/complications
• Helicobacter Infections/drug therapy
• Helicobacter Infections/therapy
• Helicobacter pylori/pathogenicity
• Aging
• Aged
• Stomach/microbiology
• Stomach/pathology
• Anti-Bacterial Agents/therapeutic use
• Probiotics/therapeutic use

• H. pylori
• antibiotic resistance
• clarithromycin
• eradication therapy
• first-line therapy
• meta-analysis
• sequential therapy
• standard triple therapy
• systematic review

• Helicobacter pylori
• bleeding peptic ulcer
• drug resistance
• gastritis
• quadruple therapy.
• randomized clinical trials

• Humans
• Bismuth/therapeutic use
• Drug Therapy, Combination
• Helicobacter Infections/drug therapy
• Helicobacter pylori
• Randomized Controlled Trials as Topic

• Helicobacter pylori
• drug resistance
• elderly
• eradication therapy
• side effect

• Humans
• Aged
• Helicobacter Infections/epidemiology
• Helicobacter Infections/diagnosis
• Helicobacter pylori
• Stomach Neoplasms/epidemiology
• Anti-Bacterial Agents/therapeutic use

• Key Science and Technology Foundation of Gansu Province
• Science and Technology Department of Gansu Province

• Acid-peptic disease
• Amoxicillin
• Antibacterial agents
• Clarithromycin
• Drug resistance
• Dyspepsia
• Esomeprazole
• H. pylori treatment regimens
• Metronidazole
• Randomized controlled trial
• Tinidazole

Introduction: Helicobacter pylori (H. pylori) colonization is prevalent all over the world, and it is associated with low socioeconomic status, poor hygiene, and overcrowding. Its eradication is important since it is an etiologic agent for gastritis, peptic ulcer, gastric carcinoma, and mucosa-associated lymphoid tissue lymphoma. Different regimens are available for the eradication of H. pylori and include triple therapy and sequential therapy. Our study aims to compare the efficacy of triple therapy versus sequential therapy in the eradication of H. pylori.

Material and methods: This randomized clinical trial was conducted at the Pakistan Institute of Medical Sciences Hospital, Islamabad, from September 2016 to September 2017 after the approval of the institutional review board. A total of 160 patients were enrolled and equally divided into two, group A and group B. A twice-daily dose of amoxicillin 1,000 mg, rabeprazole 20 mg, and clarithromycin 500 mg was given to group A for 10 days, while group B was initially given rabeprazole 20 mg and amoxicillin 1,000 mg two times daily for the first five days (i.e., induction phase), followed by triple therapy that included rabeprazole 20 mg, clarithromycin 500 mg, and metronidazole/tinidazole 500 mg twice daily for the next five days. A negative stool antigen test performed four weeks after the completion of therapy was considered an effective eradication. A proforma was used to collect data that included age, gender, city or province of residence, family income, group (group A or group B), and eradication efficacy. Analysis of the data was performed using the Statistical Package for the Social Sciences version 17 (SPSS Inc., Chicago, USA).

Results: A total of 160 patients were included, with mean age and standard deviation of 40.02±24.4 years. The male/female ratio was 1.8:1. Successful eradication of H. pylori achieved in group A was 67.5% (N=54) in comparison to group B, which was 95% (N=76) (p=0.001).

Conclusion: Sequential therapy was superior to triple therapy in H. pylori eradication.

• Bismuth
• Bismuto, Claritromicina, Helicobacter pylori
• Clarithromycin
• Helicobacter pylori
• Inhibidor de la bomba de protones
• Levofloxacin
• Levofloxacino
• Metronidazol
• Metronidazole
• Omeprazol
• Omeprazole
• Proton pump inhibitor
• Tetraciclina
• Tetracycline

• Amoxicillin/therapeutic use
• Anti-Bacterial Agents/therapeutic use
• Bismuth/therapeutic use
• Clarithromycin/therapeutic use
• Drug Therapy, Combination
• Helicobacter Infections/complications
• Helicobacter Infections/drug therapy
• Helicobacter pylori
• Humans
• Metronidazole/therapeutic use
• Peptic Ulcer/complications
• Proton Pump Inhibitors/therapeutic use

• Helicobacter pylori
• concomitant therapy
• eradication rates
• meta-analysis
• sequential therapy

• Guidelines
• Helicobacter pylori
• Meta-analysis
• Microbial sensitivity tests
• Treatment

• Humans
• Amoxicillin/therapeutic use
• Anti-Bacterial Agents/therapeutic use
• Clarithromycin/therapeutic use
• Drug Therapy, Combination
• Helicobacter Infections/diagnosis
• Helicobacter Infections/drug therapy
• Helicobacter Infections/epidemiology
• Helicobacter pylori
• Proton Pump Inhibitors/therapeutic use
• Randomized Controlled Trials as Topic
• Republic of Korea/epidemiology
• Meta-Analysis as Topic

• Amoxicillin/therapeutic use
• Anti-Bacterial Agents/adverse effects
• Bismuth/adverse effects
• Drug Therapy, Combination
• Helicobacter Infections/diagnosis
• Helicobacter Infections/drug therapy
• Helicobacter pylori
• Humans
• Proton Pump Inhibitors/adverse effects

• <i>Helicobacter pylori</i>
• Guidelines
• Meta-analysis
• Microbial sensitivity tests
• Treatment

• Helicobacter pylori
• concomitant
• hybrid
• probiotics
• vonoprazan

Antibiotic resistance is the major reason for Helicobacter pylori treatment failure, and the increasing frequency of antibiotic resistance is a challenge for clinicians. Resistance to clarithromycin and metronidazole is a particular problem. The standard triple therapy (proton pump inhibitor, amoxicillin, and clarithromycin) is no longer appropriate as the first-line treatment in most areas. Recent guidelines for the treatment of H. pylori infection recommend a quadruple regimen (bismuth or non-bismuth) as the first-line therapy. This treatment strategy is effective for areas with high resistance to clarithromycin or metronidazole, but the resistance rate inevitably increases as a result of prolonged therapy with multiple antibiotics. Novel potassium-competitive acid blocker-based therapy may be effective, but the data are limited. Tailored therapy based on antimicrobial susceptibility test results is ideal. This review discussed the current important regimens for H. pylori treatment and the optimum H. pylori eradication strategy.

• Helicobacter pylori
• antibiotic resistance
• eradication

The infection and drug resistance rates of Helicobacter pylori (H. pylori) are high and must be prevented and treated by better strategies. Based on recent research advances in this field as well as the results from our team and those on traditional Chinese medicine, we review the causes of drug resistance, and prevention and treatment strategies for drug-resistant H. pylori infection, with an aim to make suggestions for the development of new drugs, such as establishment of new target identification and screening systems, modification of existing drug structures, use of new technologies, application of natural products, and using a commercial compound library. This article may provide reference for eradication of drug-resistant H. pylori.

• Helicobacter pylori
• Drug-resistant
• Strategies
• Methods
• Treatment
• Prevention

• Helicobacter pylori
• antibiotics
• eradication
• resistance
• tailored therapy

• Concomitant therapy
• Helicobacter pylori
• Meta-analysis
• Sequential therapy

• Guideline
• Helicobacter pylori
• Korea
• Therapeutics

The efficacy of standard triple therapy (STT) in treating Helicobacter pylori infection has decreased. Many investigators have attempted to increase the eradication rate. We investigated the outcomes of concomitant therapy (CT) and STT combined with probiotics (STP) as a first-line treatment for H. pylori infection.

We reviewed the medical records of 361 patients who received either STP (n=286) or CT (n=75). The STP group received STT combined with a probiotic preparation for 1 week. The CT group received STT and metronidazole for 1 week.

The intention-to-treat and per-protocol eradication rates were 83.6% (95% confidence interval [CI], 79.0 to 87.7) and 87.1% (95% CI, 81.2 to 89.7) in the STP group and 86.7% (95% CI, 78.7 to 93.3) and 91.4% (95% CI, 83.6 to 97.1) in the CT group (p=0.512 and p=0.324), respectively. The frequency of adverse effects was higher in the CT group (28.2%) than in the STP group (12.8%) (p=0.002).

STP and CT are encouragingly efficacious as first-line treatments for H. pylori infection. Therefore, adding probiotics to STT may be a feasible option to avoid side effects.

• Helicobacter pylori
• Metronidazole
• Probiotics

• Helicobacter pylori
• bismuth salts
• concomitant therapy
• eradication

Most international guidelines recommend triple-therapy regimens consisting of a proton pump inhibitor, clarithromycin, and amoxicillin/metronidazole for at least 7 days for the eradication of Helicobacter pylori. However, the efficacy of 7-day clarithromycin-based standard triple therapy for H. pylori infection is currently unacceptable in Korea. In this study, we will compare the efficacy and safety of 7-day standard triple therapy, 10-day sequential therapy, and 10-day concomitant therapy for the first-line treatment of H. pylori infection in Korea.

In this multicenter, investigator-blinded, randomized trial we are recruiting adult patients with H. pylori infection from 15 hospitals in Korea to determine whether sequential or concomitant treatment is superior to standard triple therapy. Patients are randomly assigned to receive either standard triple therapy (lansoprazole, amoxicillin, and clarithromycin) for 7 days, or sequential treatment (lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, clarithromycin, and metronidazole for another 5 days) for 10 days, or concomitant therapy (lansoprazole, amoxicillin, clarithromycin, and metronidazole) for 10 days. The primary outcome is the rate of H. pylori eradication in the intention-to-treat population.

The results of this study will be crucial for determining the optimal regimen for the primary treatment of H. pylori infection in Korea. This study will produce vital evidence that will lead to revisions to guidelines concerning first-line treatment regimens for H. pylori infection.

Clinical Research Information Service (CRIS), Republic of Korea, KCT0001980. Registered on 25 July 2016.

The online version of this article (doi:10.1186/s13063-017-2281-0) contains supplementary material, which is available to authorized users.

• Concomitant therapy
• Helicobacter pylori
• Sequential therapy
• Triple therapy

• Helicobacter pylori
• amoxicillin
• bismuth
• clarithromycin
• concomitant
• high dose
• levofloxacin
• metronidazole
• nonbismuth
• optimization
• optimized
• sequential

• Helicobacter pylori
• antibiotics
• eradication therapy
• network meta-analysis
• tolerability

To evaluate the adjuvant effects of N-acetylcysteine (NAC) on first-line sequential therapy (SQT) for Helicobacter pylori infection.

Patients with H. pylori infections were randomly assigned to receive sequential therapy with (SQT+NAC group, n=49) or without (SQT-only group, n=50) NAC. Sequential therapy consisted of rabeprazole 20 mg and amoxicillin 1 g for the first 5 days, followed by rabeprazole 20 mg, clarithromycin 500 mg and metronidazole 500 mg for the remaining 5 days; all drugs were administered twice daily. For the SQT+NAC group, NAC 400 mg bid was added for the first 5 days of sequential therapy. H. pylori eradication was evaluated 4 weeks after the completion of therapy.

The eradication rates by intention-to-treat analysis were 58.0% in the SQT-only group and 67.3% in the SQT+NAC group (p=0.336). The eradication rates by per-protocol analysis were 70.0% in the SQT-only group and 80.5% in the SQT+NAC group (p=0.274). Compliance was very good in both groups (SQT only/SQT+NAC groups: 95.2%/100%, p=0.494). There was no significant difference in the adverse event rates between groups (SQT-only/SQT+NAC groups: 26.2%/26.8%, p=0.947).

The H. pylori eradication rate was numerically higher in the SQT+NAC group than in the SQT-only group. As our data did not reach statistical significance, larger trials are warranted.

• Eradication
• Helicobacter pylori
• N-acetylcysteine
• Sequential therapy

• Helicobacter pylori
• drug therapy and general practice
• gastric cancer
• peptic ulcer

• Epidemiology
• Helicobacter pylori
• Peptic ulcer
• Prevalence
• Therapy

• GASTRITIS
• HELICOBACTER PYLORI
• HELICOBACTER THERAPY

• Concomitant
• Greece
• Helicobacter pylori
• sequential

• Clarithromycin resistance
• Concomitant treatment
• First line
• H. pylori treatment
• Metronidazole resistance
• Sequential treatment

• Adult
• Aged
• Amoxicillin/administration & dosage
• Anti-Bacterial Agents/administration & dosage
• Biopsy
• Breath Tests
• Carbon Isotopes
• Clarithromycin/administration & dosage
• Drug Resistance, Bacterial
• Drug Therapy, Combination
• Dyspepsia/drug therapy
• Dyspepsia/microbiology
• Esomeprazole/administration & dosage
• Female
• Helicobacter Infections/drug therapy
• Helicobacter Infections/metabolism
• Helicobacter Infections/pathology
• Helicobacter pylori
• Humans
• Male
• Metronidazole/administration & dosage
• Middle Aged
• Peptic Ulcer/drug therapy
• Peptic Ulcer/microbiology
• Proton Pump Inhibitors/administration & dosage
• Pyloric Antrum/pathology
• Urea/metabolism

• Adult
• Drug Therapy, Combination/methods
• Geography, Medical
• Helicobacter Infections/drug therapy
• Helicobacter pylori
• Humans
• Intention to Treat Analysis
• Randomized Controlled Trials as Topic

• Bismuth
• Bismuto
• Clarithromycin
• Claritromicina
• Helicobacter pylori
• Inhibidor de la bomba de protones
• Metronidazol
• Metronidazole
• Omeprazol
• Omeprazole
• Proton pump inhibitor

• Helicobacter pylori
• concomitant
• resistance
• susceptibility
• therapy

• antibiotic therapy
• helicobacter pylori eradication
• patient compliance
• peptic ulcer perforation

Background. The decline of Helicobacter pylori (H. pylori) eradication rates with standard triple therapy resulted in a search for novel therapies for first-line therapy of H. pylori infection. Aim. The aim of the study is to compare the efficacy of concomitant therapy with sequential therapy as the first-line therapy of H. pylori eradication. Methods. We reviewed medical records of patients who were confirmed to have H. pylori infection and received eradication treatment from September 2012 to March 2015. The concomitant group was treated with rabeprazole, amoxicillin, clarithromycin, and metronidazole for 7 days. The sequential group was treated with rabeprazole and amoxicillin for 5 days and then rabeprazole, clarithromycin, and metronidazole for an additional 5 days. Six weeks after the treatment period, patients in both groups underwent 13C-Urea breath test (UBT) to confirm H. pylori eradication. Results. The eradication rate was 90.3% in the concomitant group and 85.5% in the sequential group. However, the eradication rates between the two groups showed no statistical difference (P = 0.343). Conclusion. No statistical difference was found in eradication rates between the two groups. However, in areas where antibiotic resistance is high, concomitant therapy may be more effective than sequential therapy for H. pylori eradication.

Helicobacter pylori (H. pylori) plays a role in the pathogenesis of gastric cancer. The outcome of the infection depends on environmental factors and bacterial and host characteristics. Gastric carcinogenesis is a multistep process that is reversible in the early phase of mucosal damage, but the exact point of no return has not been identified. Therefore, two main therapeutic strategies could reduce gastric cancer incidence: (1) eradication of the already present infection; and (2) immunization (prior to or during the course of the infection). The success of a gastric cancer prevention strategy depends on timing because the prevention strategy must be introduced before the point of no return in gastric carcinogenesis. Although the exact point of no return has not been identified, infection should be eradicated before severe atrophy of the gastric mucosa develops. Eradication therapy rates remain suboptimal due to increasing H. pylori resistance to antibiotics and patient noncompliance. Vaccination against H. pylori would reduce the cost of eradication therapies and lower gastric cancer incidence. A vaccine against H. pylori is still a research challenge. An effective vaccine should have an adequate route of delivery, appropriate bacterial antigens and effective and safe adjuvants. Future research should focus on the development of rescue eradication therapy protocols until an efficacious vaccine against the bacterium becomes available.

• Helicobacter pylori
• Gastric cancer
• Vaccine
• Eradication therapy
• Prevention

• Animals
• Anti-Bacterial Agents/therapeutic use
• Bacterial Vaccines/therapeutic use
• Cell Transformation, Neoplastic/pathology
• Disease Models, Animal
• Drug Resistance, Bacterial
• Gastric Mucosa/drug effects
• Gastric Mucosa/immunology
• Gastric Mucosa/microbiology
• Gastric Mucosa/pathology
• Helicobacter Infections/complications
• Helicobacter Infections/drug therapy
• Helicobacter Infections/microbiology
• Helicobacter pylori/drug effects
• Helicobacter pylori/immunology
• Helicobacter pylori/pathogenicity
• Host-Pathogen Interactions
• Humans
• Protective Factors
• Risk Factors
• Stomach Neoplasms/microbiology
• Stomach Neoplasms/pathology
• Stomach Neoplasms/prevention & control

Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori) has been associated with gastro-duodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacillus. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication.

• Helicobacter pylori
• Treatment
• Antibiotic resistance
• Therapeutic regimens
• Novel agents

• concomitant
• hybrid
• optimization
• probiotics
• sequential
• standard triple therapy

• Bismuth
• Concomitant
• Eradication
• Helicobacter pylori
• Quadruple
• Resistance
• Therapy
• Triple

• Antacids/therapeutic use
• Anti-Bacterial Agents/therapeutic use
• Bismuth/therapeutic use
• Drug Therapy, Combination
• Helicobacter Infections/drug therapy
• Helicobacter pylori
• Humans
• Probiotics/therapeutic use
• Proton Pump Inhibitors/therapeutic use
• Treatment Outcome

• Helicobacter pylori
• concomitant therapy
• meta-analysis
• sequential therapy

AIM: To evaluate the efficacy of 14-d moxifloxacin-based sequential therapy as first-line eradication treatment of Helicobacter pylori (H. pylori) infection.

METHODS: From December 2013 to August 2014, 161 patients with confirmed H. pylori infection randomly received 14 d of moxifloxacin-based sequential group (MOX-ST group, n = 80) or clarithromycin-based sequential group (CLA-ST group, n = 81) therapy. H. pylori infection was defined on the basis of at least one of the following three tests: a positive ¹³C-urea breath test; histologic evidence of H. pylori by modified Giemsa staining; or a positive rapid urease test (CLOtest; Delta West, Bentley, Australia) by gastric mucosal biopsy. Successful eradication therapy for H. pylori infection was defined as a negative ¹³C-urea breath test four weeks after the end of eradication treatment. Compliance was defined as good when drug intake was at least 85%. H. pylori eradication rates, patient compliance with drug treatment, adverse event rates, and factors influencing the efficacy of eradication therapy were evaluated.

RESULTS: The eradication rates by intention-to-treat analysis were 91.3% (73/80; 95%CI: 86.2%-95.4%) in the MOX-ST group and 71.6% (58/81; 95%CI: 65.8%-77.4%) in the CLA-ST group (P = 0.014). The eradication rates by per-protocol analysis were 93.6% (73/78; 95%CI: 89.1%-98.1%) in the MOX-ST group and 75.3% (58/77; 95%CI: 69.4%-81.8%) in the CLA-ST group (P = 0.022). Compliance was 100% in both groups. The adverse event rates were 12.8% (10/78) and 24.6% (19/77) in the MOX-ST and CLA-ST group, respectively (P = 0.038). Most of the adverse events were mild-to-moderate in intensity; there was none serious enough to cause discontinuation of treatment in either group. In multivariate analysis, advanced age (≥ 60 years) was a significant independent factor related to the eradication failure in the CLA-ST group (adjusted OR = 2.13, 95%CI: 1.97-2.29, P = 0.004), whereas there was no significance in the MOX-ST group.

CONCLUSION: The 14-d moxifloxacin-based sequential therapy is effective. Moreover, it shows excellent patient compliance and safety compared to the 14-d clarithromycin-based sequential therapy.

• Helicobacter pylori
• First-line eradication treatment
• Moxifloxacin
• Sequential therapy
• Eradication rate

• Aged
• Anti-Bacterial Agents/administration & dosage
• Anti-Bacterial Agents/adverse effects
• Biopsy
• Breath Tests
• Clarithromycin/administration & dosage
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Fluoroquinolones/administration & dosage
• Fluoroquinolones/adverse effects
• Helicobacter Infections/diagnosis
• Helicobacter Infections/drug therapy
• Helicobacter Infections/microbiology
• Helicobacter pylori/drug effects
• Helicobacter pylori/isolation & purification
• Humans
• Intention to Treat Analysis
• Male
• Medication Adherence
• Metronidazole/administration & dosage
• Middle Aged
• Moxifloxacin
• Multivariate Analysis
• Odds Ratio
• Pilot Projects
• Predictive Value of Tests
• Prospective Studies
• Proton Pump Inhibitors/administration & dosage
• Rabeprazole/administration & dosage
• Republic of Korea
• Stomach Diseases/diagnosis
• Stomach Diseases/drug therapy
• Stomach Diseases/microbiology
• Time Factors
• Treatment Outcome

• Anti-Bacterial Agents/administration & dosage
• Data Interpretation, Statistical
• Drug Administration Schedule
• Drug Therapy, Combination
• Helicobacter Infections/drug therapy
• Helicobacter pylori/drug effects
• Humans

Helicobacter pylori (H. pylori) is a major human pathogen associated with significant morbidity and mortality. However, after decades of efforts, treatment of H. pylori remains a challenge for physicians, as there is no universally effective regimen. Due to the rising prevalence of antimicrobial resistance, mainly to clarithromycin, efficacy of standard triple therapies has declined to unacceptably low levels in most parts of the world. Novel regimens, specifically experimented to improve the therapeutic outcome against antibiotic-resistant H. pylori strains, are now recommended as first-line empirical treatment options providing high efficacy (reportedly > 90% in intention to treat analysis) even in high clarithromycin resistance settings. These include the bismuth quadruple, concomitant, sequential and hybrid therapies. Due to the rapid development of quinolone resistance, levofloxacin-based regimens should be reserved as second-line/rescue options. Adjunct use of probiotics has been proposed in order to boost eradication rates and decrease occurrence of treatment-related side effects. Molecular testing methods are currently available for the characterization of H. pylori therapeutic susceptibility, including genotypic detection of macrolide resistance and evaluation of the cytochrome P450 2C19 status known to affect the metabolism of proton pump inhibitors. In the future, use of these techniques may allow for culture-free, non-invasive tailoring of therapy for H. pylori infection.

• Helicobacter pylori
• Antibiotic resistance
• Bismuth-quadruple
• Concomitant
• Sequential
• Probiotics

• Adverse events
• dyspepsia
• eradication
• gastritis
• pylori