Nucleotide Binding Oligomerization Domain 1 Is an Essential Signal Transducer in Human Epithelial Cells Infected with Helicobacter pylori That Induces the Transepithelial Migration of Neutrophils

Background/Aims

The cytosolic host protein nucleotide binding oligomerization domain 1 (Nod1) has emerged as a key pathogen recognition molecule for innate immune responses in epithelial cells. The purpose of the study was to elucidate the mechanism by which Helicobacter pylori infection leads to transepithelial neutrophil migration in a Nod1-mediated manner.

Methods

Human epithelial cell lines AGS and Caco-2 were grown and infected with H. pylori. Interleukin (IL)-8 mRNA expression and IL-8 secretion were assessed, and nuclear factor κB (NF-κB) activation was determined. Stable transfections of AGS and Caco-2 cells with dominant negative Nod1 were generated. Neutrophil migration across the monolayer was quantified.

Results

Cytotoxin-associated gene pathogenicity island (cagPAI)(+) H. pylori infection upregulated IL-8 mRNA expression and IL-8 secretion in AGS and Caco-2 cells compared with controls. NF-κB activation, IL-8 mRNA expression and IL-8 secretion by cagPAI knockdown strains were reduced compared with those infected with the wild-type strain. NF-κB activation, IL-8 mRNA expression and IL-8 secretion in dominant-negative (DN)-Nod1 stably transfected cells were reduced compared with the controls. The transepithelial migration of neutrophils in DN-Nod1 stably transfected cells was reduced compared with that in controls.

Conclusions

Signaling through Nod1 plays an essential role in neutrophil migration induced by the upregulated NF-κB activation and IL-8 expression in H. pylori-infected human epithelial cells.     

Antimicrobial susceptibility of Canadian isolates of Helicobacter pylori in Northeastern Ontario

BACKGROUND:

Helicobacter pylori plays a significant role in gastritis and ulcers. It is a carcinogen as defined by the WHO, and infection can result in adenocarcinomas and mucosa-associated lymphoid tissue lymphomas. In Canada, rates of antimicrobial resistance are relatively unknown, with very few studies conducted in the past 15 years.

OBJECTIVE:

To examine rates of resistance in Sudbury, Ontario, compare antimicrobial susceptibility methods and attempt to determine the molecular basis of antibiotic resistance.

METHODS:

Patients attending scheduled visits at Health Sciences North (Sudbury, Ontario) provided gastric biopsy samples on a volunteer basis. In total, 20 H pylori isolates were collected, and antimicrobial susceptibility testing (on amoxicillin, tetracycline, metronidazole, ciprofloxacin, levofloxacin and clarithromycin) was conducted using disk diffusion and E-test methods. Subsequently, genomic DNA from these isolates was sequenced to detect mutations associated with antimicrobial resistance.

RESULTS:

Sixty-five percent of the isolates were found to be resistant to at least one of the listed antibiotics according to E-test. Three isolates were found to be resistant to ≥3 of the above-mentioned antibiotics. Notably, 25% of the isolates were found to be resistant to both metronidazole and clarithromycin, two antibiotics that are normally prescribed as part of first-line regimens in the treatment of H pylori infections in Canada and most of the world. Among the resistant strains, the sequences of 23S ribosomal RNA and gyrA, which are linked to clarithromycin and ciprofloxacin/levofloxacin resistance, respectively, revealed the presence of known point mutations associated with antimicrobial resistance.

CONCLUSIONS:

In general, resistance to metronidazole, ciprofloxacin/levofloxacin and clarithromycin has increased since the studies in the early 2000s. These results suggest that surveillance programs of H pylori antibiotic resistance may need to be revisited or improved to prevent antimicrobial therapy failure.     

Prevalence of primary Helicobacter pylori resistance to metronidazole and clarithromycin in Singapore

INTRODUCTION Eradication of Helicobacter pylori, a bacterium residing in stomach and causing peptic ulcer disease,can be achieved by using combination therapies consisting of one or two antibiotics with a proton pump inhibitor (PPI). The major antibiotics widely used in the regimens to eradicate H. Pylori are metronidazole and clarithromycin[1-3].     

Different antibiotic susceptibility between antrum and corpus of the stomach,a possible reason for treatment failure of Helicobacter pylori infection

AIM:To assess whether antibiotic resistance varies between the antrum and corpus of the stomach of patients that are either Helicobacter pylori(H.pylori)therapy-naive or pre-treated.METHODS:H.pylori strains were isolated from antrum and corpus biopsies from 66 patients that received a diagnostic gastroduodenoscopy for variant clinical indications.Antimicrobial susceptibility to amoxicillin,clarithromycin,tetracycline,metronidazole,levofloxacin and rifabutin was tested with the E-test method on IsoSensitest agar with 10 vol%defibrinated horse blood.In patients with a different antibiotic susceptibility pattern between the isolates from the antrum and corpus,DNA fingerprinting via random amplified polymorphic DNA analysis was performed to detect differences among DNA patterns of H.pylori isolates.RESULTS:Primary,secondary and tertiary resistance to clarithromycin was 6.9%,53.8%and 83.3%,retrospectively.Metronidazole and levofloxacin resistance also increased according to the number of previous treatments(17.2%,69.2%,83.3%;13.8%,23.1%,33.3%).Tertiary resistance to rifabutin was detected in12.5%of patients.In none of the 66 patients a resistance against amoxicillin or tetracycline was detectable.Discordant antibiotic susceptibility between antrum and corpus isolates for different antibiotics was seen in 15.2%(10/66)of the patients.Two out of those ten patients were naive to any H.pylori antibiotic treatment.The remaining eight patients previously received at least one eradication therapy.DNA fingerprinting analysis revealed no substantial differences among DNA patterns between antrum and corpus isolates in the majority of patients suggesting an infection with a single H.pylori strain.CONCLUSION:Different antibiotic susceptibility between antrum and corpus biopsies is a common phenomenon and a possible explanation for treatment failure.Resistant H.pylori strains may be missed if just one biopsy from one anatomic site of the stomach is taken for H.pylori susceptibility testing.     

Clinical significance of Helicobacter pylori cagA and iceA genotype status

AIM:To study the presence of Helicobacter pylori(H.pylori) virulence factors and clinical outcome in H.pylori infected patients.METHODS:A prospective analysis of ninety nine H.pylori-positive patients who underwent endoscopy in our Endoscopy suite were included in this study.DNA was isolated from antral biopsy samples and the presence of cagA,iceA,and iceA2 genotypes were determined by polymerase chain reaction and a reverse hybridization technique.Screening for H.pylori infection was performed in all patie...     

Antibiotic resistance and cagA gene correlation: a looming crisis of Helicobacter pylori

AIM: To determine antibiotic resistance of Helicobacter pylori (H. pylori) in Pakistan and its correlation with host and pathogen associated factors.METHODS: A total of 178 strains of H. pylori were isolated from gastric biopsies of dyspeptic patients. Susceptibility patterns against first and second-line antibiotics were determined and trends of resistance were analyzed in relation to the sampling period, gastric conditions and cagA gene carriage. The effect of cagA gene on the acquisition of resistance was investigated by mutant selection assay.RESULTS: The observations showed that monoresistant strains were prevalent with rates of 89% for metronidazole, 36% for clarithromycin, 37% for amoxicillin, 18.5% for ofloxacin and 12% for tetracycline. Furthermore, clarithromycin resistance was on the rise from 2005 to 2008 (32% vs 38%, P = 0.004) and it is significantly observed in non ulcerative dyspeptic patients compared to gastritis, gastric ulcer and duodenal ulcer cases (53% vs 20%, 18% and 19%, P = 0.000). On the contrary, metronidazole and ofloxacin resistance were more common in gastritis and gastric ulcer cases. Distribution analysis and frequencies of resistant mutants in vitro correlated with the absence of cagA gene with metronidazole and ofloxacin resistance.CONCLUSION: The study confirms the alarming levels of antibiotic resistance associated with the degree of gastric inflammation and cagA gene carriage in H. pylori strains.     

Helicobacter pylori acquistion of metronidazole resistance by natural transformation in vitro

AIM: To study whether Helicobacter pylori is naturally transformable.METHODS: Transformation was performed in BHI broth supplemented with horse serum and yeast extract. Genomic DNA extracted from a metronidazole resistant H.pylori strain was added to H. pylori broth culture. The mixture was incubated at microaerophilic atmosphere. The DNA-treated cells were plated on blood agar containing 8 mg/L metronidazole to select for transformants. Sterile distilled water was used as a negative DNA control. The DNA profiles of transformants were compared with that of their parent strains by randomly amplified polymorphic DNA (RAPD) fingerprinting.RESULTS: Transformation of H. pylori with DNA from a metronidazole resistant strain as a marker was demonstrated. Out of the 12 strains of H. pylori tested, 9 (75%) strains were found to be transformable. The transformation frequencies ranged from 3.4 × 10^-6 to 2.4 × 10^-4. By RAPD, DNA fingerprints of the transformants and their parent strains showed no change in DNA profiles though transformants were all resistant to metronidazole as compared with their metronidazole-sensitive parent strains.CONCLUSION: Helicobacter pylori is naturally transformable which might be one of the ways that H. pylori develops resistance to metronidazole.     

Prevalence of Helicobacter pylori virulence genotypes among children in Eastern Turkey

AIM:To identify the virulence genotypes of Helicobacter pylori(H.pylori)if present in children in Eastern Turkey and if those genotypes are mostly associated with severe clinical presentations.METHODS:A total of 49 H.pylori positive Turkish children(42 with antral nodularity and 7 with peptic ulcer)who underwent upper gastrointestinal endoscopy with abdominal symptoms during the period from March 2011 to September 2012 were enrolled in this study.Antral nodularity was diagnosed endoscopically by two of the authors.We determined for the presence of cagA,vacA,cagE,iceA and babA2 genotypes of H.pylori isolates in DNA obtained directly from frozen gastric biopsy samples by polymerase chain reaction test using specific primers.RESULTS:Of the 49 H.pylori isolates studied,61.2%,91.8%,22.4%,28.6%,57.1%and 40.8%were positive for the cagA,vacA s1,cagE,iceA1,iceA2 and babA2 genes,respectively.We showed that the most common vacA subtype was s1a(79.6%).However,the s2 gene was found less frequently with an isolation rate of 8.2%of the H.pylori isolates.The genotypes iceA2 and vacA s1m2 were the most frequently found types in children with antral nodularity.In addition,the genotypes iceA1,babA2 and vacA s1m1 were found in similar ratios in all the H.pylori isolates obtained from children with peptic ulcer.The genotypes vacA s2m1and s1c were not observed in any of isolates studied.CONCLUSION:This study showed that vacA s1m2,cagA and iceA2 were the most common genotypes,and no association between antral nodularity and genotypes was observed.     

Antimicrobial susceptibility testing for Helicobacter pylori in times of increasing antibiotic resistance

The gram-negative bacterium Helicobacter pylori(H.pylori)causes chronic gastritis,gastric and duodenal ulcers,gastric cancer and mucosa-associated lymphoid tissue lymphoma.Treatment is recommended in all symptomatic patients.The current treatment options for H.pylori infection are outlined in this review in light of the recent challenges in eradication success,largely due to the rapid emergence of antibiotic resistant strains of H.pylori.Antibiotic resistance is a constantly evolving process and numerous studies have shown that the prevalence of H.pylori antibiotic resistance varies significantly from country to country,and even between regions within the same country.In addition,recent data has shown that previous antibiotic use is associated with harbouring antibiotic resistant H.pylori.Local surveillance of antibiotic resistance is warranted to guide clinicians in their choice of therapy.Antimicrobial resistance is assessed by H.pylori culture and antimicrobial susceptibility testing.Recently developed molecular tests offer an attractive alternative to culture and allow for the rapid molecular genetic identification of H.pylori and resistance-associated mutations directly from biopsy samples or bacterial culture material.Accumulating evidence indicates that surveillance of antimicrobial resistance by susceptibility testing is feasible and necessary to inform clinicians in their choice of therapy for management of H.pylori infection.     

Helicobacter pylori and CagA under conditions of iron deficiency

Iron deficiency is the most common nutritional deficiency worldwide and compelling evidence has demonstrated that this condition heightens the risk of gastric cancer. Infection with Helicobacter pylori is the strongest known risk factor for the development of gastric adenocarcinoma. Recent work has demonstrated that, under conditions of iron deficiency, H. pylori-induced gastric carcinogenesis is augmented through increased formation of the strain-specific cag type IV secretion system and enhanced delivery of the bacterial oncoprotein CagA into host cells. Although CagA is a potent virulence factor that promotes oncogenic responses, additional studies have now demonstrated that CagA modulates host cell iron homeostasis in vitro and fundamental metabolic functions of the bacterial cell in vivo. Here we discuss these findings and describe working models by which CagA exerts its effects on gastric epithelial cells, with particular emphasis on its potential role in modulation of host iron homeostasis.     

Helicobacter pylori in Thai patients with cholangiocarcinoma and its association with biliary inflammation and proliferation

Objectives

To investigate whether Helicobacter spp. infection and the cagA of H. pylori are associated with hepatobiliary pathology, specifically biliary inflammation, cell proliferation and cholangiocarcinoma (CCA).

Methods

Helicobacter species including H. pylori, H. bilis and H. hepaticus were detected in the specimens using the polymerase chain reaction (PCR). Biliary inflammation of the liver and gallbladders was semi-quantitatively graded on hematoxylin and eosin (H&E)-stained slides. Biliary proliferation was evaluated by immunohistochemistry using the Ki-67-labelling index.

Results

Helicobacter pylori was found in 66.7%, 41.5% and 25.0% of the patients in the CCA, cholelithiasis and control groups (P < 0.05), respectively. By comparison, H. bilis was found in 14.9% and 9.4% of the patients with CCA and cholelithiasis, respectively (P > 0.05), and was absent in the control group. The cagA gene of H. pylori was detected in 36.2% and 9.1% of the patients with CCA and cholelithiasis, respectively (P < 0.05). Among patients with CCA, cell inflammation and proliferation in the liver and gallbladder were significantly higher among those DNA H. pylori positive than negative.

Conclusions

The present findings suggest that H. pylori, especially the cagA-positive strains, may be involved in the pathogenesis of hepatobiliary diseases, especially CCA through enhanced biliary cell inflammation and proliferation.     

Levofloxacin,Metronidazole, and Lansoprazole Triple Therapy Compared to Quadruple Therapy as a Second-Line Treatment of Helicobacter pylori Infection in Korea

Background/Aims

Several rescue therapies have been recommended to eradicate Helicobacter pylori infection in patients with a failure of first-line eradication therapy, but they still fail in more than 20% of cases. The aim of this study was to evaluate the efficacy and safety of levofloxacin, metronidazole, and lansoprazole (LML) triple therapy relative to quadruple therapy as a second-line treatment.

Methods

In total, 113 patients who failed first-line triple therapy for H. pylori infection were randomly assigned to two groups: LML for 7 days and tetracycline, bismuth subcitrate, metronidazole and lansoprazole (quadruple) for 7 days.

Results

According to intention-to-treat analysis, the infection was eradicated in 38 of 56 patients (67.9%) in the LML group and 48 of 57 (84.2%) in the quadruple group (p=0.042). Per-protocol analysis showed successful eradication in 38 of 52 patients (73.1%) from the LML group and 48 of 52 (92.3%) from the quadruple group (p=0.010). There were no significant differences in the adverse effects in either treatment group.

Conclusions

LML therapy is less effective than quadruple therapy as a second-line treatment for H. pylori infection. Therefore, quadruple therapy should be considered as the primary second-line strategy for patients experiencing a failure of first-line H. pylori therapy in Korea.     

Efficacy of tailored Helicobacter pylori eradication therapy based on antibiotic susceptibility and CYP2C19 genotype

The cure rates of Helicobacter pylori(H.pylori)eradication therapy using a proton pump inhibitor(PPI)and antimicrobial agents such as amoxicillin,clarithromycin,and metronidazole are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of the inhibition of acid secretion.Annual cure rates have gradually decreased because of the increased prevalence of H.pylori strains resistant to antimicrobial agents,especially to clarithromycin.Alternative regimens have therefore been developed incorporating different antimicrobial agents.Further,standard PPI therapy(twice-daily dosing)often fails to induce a long-term increase in intragastric pH>4.0.Increasing the eradication rate requires more frequent and higher doses of PPIs.Therapeutic efficacy related to acid secretion is influenced by genetic factors such as variants of the genes encoding drug-metabolizing enzymes(e.g.,cytochrome P450 2C19,CYP2C19),drug transporters(e.g.,multidrug resistance protein-1;ABCB1),and inflammatory cytokines(e.g.,interleukin-1β).For example,quadruple daily administration of PPI therapy potently inhibits acid secretion within 24 h,irrespective of CYP2C19 genotype.Therefore,tailored H.pylori eradication regimens that address acid secretion and employ optimal antimicrobial agents based on results of antimicrobial agent-susceptibility testing may prove effective in attaining higher eradication rates.     

Antibiotic Susceptibility Profile of Helicobacter pylori Isolated from the Dyspepsia Patients in Tehran, Iran

Background/Aim:

Helicobacter pylori is an important pathogen for gastroduodenal diseases. Infection with H. pylori can be limited by regimens of multiple antimicrobial agents. However, antibiotic resistance is a leading cause of treatment failure. The aim of this study has been to determine the resistance patterns of H. pylori strains isolated from gastric biopsies of patients with dyspepsia by agar dilution method, in Tehran, Iran

Patients and Methods:

H. pylori isolates from patients with gastrointestinal diseases were evaluated for susceptibility testing by agar dilution method. Susceptibility testing was performed to commonly used antibiotics including clarithromycin, tetracycline, amoxicillin, metronidazole and ciprofloxacin.

Results:

Among 92 patients with dyspepsia, H. pylori strains were isolated from 42 patients. Seventeen (40.5%) of the isolates were resistant to metronidazole (MICs ≥ 8 μg/l), whereas one isolate (2.4%) was resistant to amoxicillin (MICs ≤ 0. 5 μg/ml) and ciprofloxacin (MICs ≤ 1μg/ml). The resistance rates to other antibiotics in H. pylori isolates are recorded as follows: clarithromycin 6 (14.3 %), tetracycline 2 (4.8%). In 5 of 42 resistant cases, combined resistance was found.

Conclusions:

These data suggest that metronidazole should be used among Iranian patients in first-line therapy with caution, and ciprofloxacin in association with amoxicillin and a proton pump inhibitor is more recommended.     

Vacuoles of Candida yeast as a specialized niche for Helicobacter pylori

Helicobacter pylori(H.pylori)are resistant to hostile gastric environments and antibiotic therapy,reflecting the possibility that they are protected by an ecological niche,such as inside the vacuoles of human epithelial and immune cells.Candida yeast may also provide such an alternative niche,as fluorescently labeled H.pylori were observed as fast-moving and viable bacterium-like bodies inside the vacuoles of gastric,oral,vaginal and foodborne Candida yeasts.In addition,H.pylori-specific genes and proteins were detected in samples extracted from these yeasts.The H.pylori present within these yeasts produce peroxiredoxin and thiol peroxidase,providing the ability to detoxify oxygen metabolites formed in immune cells.Furthermore,these bacteria produce urease and VacA,two virulence determinants of H.pylori that influence phago-lysosome fusion and bacterial survival in macrophages.Microscopic observations of H.pylori cells in new generations of yeasts along with amplification of H.pylori-specific genes from consecutive generations indicate that new yeasts can inherit the intracellular H.pylori as part of their vacuolar content.Accordingly,it is proposed that yeast vacuoles serve as a sophisticated niche that protects H.pylori against the environmental stresses and provides essential nutrients,including ergosterol,for its growth and multiplication.This intracellular establishment inside the yeast vacuole likely occurred long ago,leading to the adaptation of H.pylori to persist in phagocytic cells.The presence of these bacteria within yeasts,including foodborne yeasts,along with the vertical transmission of yeasts from mother to neonate,provide explanations for the persistence and propagation of H.pylori in the human population.This Topic Highlight reviews and discusses recent evidence regarding the evolutionary adaptation of H.pylori to thrive in host cell vacuoles.     

Helicobacter pylori and skin autoimmune diseases

Autoimmune skin diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to skin self-antigen(s). The prolonged interaction between the bacterium and host immune mechanisms makes Helicobacter pylori(H. pylori) a plausible infectious agent for triggering autoimmunity. Epidemiological and experimental data now point to a strong relation of H. pylori infection on the development of many extragastric diseases, including several allergic and autoimmune diseases. H. pylori antigens activate cross-reactive T cells and induce autoantibodies production. Microbial heat shock proteins(HSP) play an important role of in the pathogenesis of autoimmune diseases because of the high level of sequence homology with human HSP. Eradication of H. pylori infection has been shown to be effective in some patients with chronic autoimmune urticaria, psoriasis, alopecia areata and Schoenlein-Henoch purpura. There is conflicting and controversial data regarding the association of H. pylori infection with Beh et’s disease, scleroderma and autoimmune bullous diseases. No data are available evaluating the association of H. pylori infection with other skin autoimmune diseases, such as vitiligo, cutaneous lupus erythematosus and dermatomyositis. The epidemiological and experimental evidence for a possible role of H. pylori infection in skin autoimmune diseases are the subject of this review.     

Helicobacter pylori CagA protein polymorphisms and their lack of association with pathogenesis

AIM: To investigate Helicobacter pylori (H. pylori) CagA diversity and to evaluate the association between protein polymorphisms and the occurrence of gastric pathologies. METHODS: One hundred and twenty-two clinical isolates of H. pylori cultured from gastric biopsies obtained from Colombian patients with dyspepsia were included as study material. DNA extracted from isolates was used to determine cagA status, amplifying the C-terminal cagA gene region by polymerase chain reaction. One hundred and six strai...     

Helicobacter pylori isolates from ethnic minority patients in Guangxi:Resistance rates,mechanisms,and genotype

AIM:To investigate the rate of Helicobacter pylori（H.pylori）resistance to clarithromycin among ethnic minority patients in Guangxi,explore the underlyingmechanisms,and analyze factors influencing genotype distribution of H.pylori isolates.METHODS:H.pylori strains were isolated,cultured and subjected to drug sensitivity testing.The 23S rRNA gene of H.pylori isolates was amplified by PCR and analyzed by PCR-RFLP and direct sequencing to detect point mutations.REP-PCR was used for genotyping of H.pylori isolates,and NTsys₂ software was used for clustering analysis based on REP-PCR DNA fingerprints.Factors potentially influencing genotype distribution of H.pylori isolates were analyzed.RESULTS:The rate of clarithromycin resistance was31.3%.A2143G and A2144G mutations were detected in the 23S rRNA gene of all clarithromycin-resistant H.pylori isolates.At a genetic distance of 78%,clarithromycin-resistant H.pylori isolates could be divided into six groups.Significant clustering was noted among H.pylori isolates from patients with peptic ulcer or gastritis.CONCLUSION:The rate of clarithromycin resistance is relatively high in ethnic minority patients in Guangxi.Main mechanisms of clarithromycin resistance are A2143G and A2144G mutations in the 23S rRNA gene.Clarithromycin-resistant H.pylori isolates can be divided into six groups based on REP-PCR DNA fingerprints.Several factors such as disease type may influence the genotype distribution of H.pylori isolates.     

Helicobacter pylori eradication: Sequential therapy and Lactobacillus reuteri supplementation

AIM:To evaluate the role of sequential therapy and Lactobacillus reuteri (L. reuteri ) supplementation, in the eradication treatment of Helicobacter pylori (H. pylori ). METHODS:H. pylori infection was diagnosed in 90 adult dyspeptic patients. Patients were excluded if previously treated for H. pylori infection or if they were taking a proton pump inhibitor (PPI), H2-receptor antagonist or antibiotics. Patients were assigned to receive one of the following therapies:(1) 7-d triple therapy (PPI plus clarithromycin and amoxicillin or metronidazole) plus L. reuteri supplementation dur- ing antibiotic treatment; (2) 7-d triple therapy plus L. reuteri supplementation after antibiotic treatment; (3) sequential regimen (5-d PPI plus amoxicillin therapy followed by a 5-d PPI, clarithromycin and tinidazole) plus L. reuteri supplementation during antibiotic treatment; and (4) sequential regimen plus L. reuteri supplementation after antibiotic treatment. Successful eradication therapy was defined as a negative urea breath test at least 4 wk following treatment. RESULTS:Ninety adult dyspeptic patients were en- rolled, and 83 (30 male, 53 female; mean age 57 ± 13 years) completed the study. Nineteen patients were administered a 7-d triple treatment:11 with L. reuteri supplementation during and 8 after therapy. Sixty-four patients were administered a sequential regimen:32 with L. reuteri supplementation during and 32 after therapy. The eradication rate was significantly higher in the sequential group compared with the 7-d triple regimen (88% vs 63%, P = 0.01). No difference was found between two types of PPI. No difference in erad- ication rates was observed between patients submitted to L. reuteri supplementation during or after antibiotic treatment. Compliance with therapy was excellent in all patients. No difference in adverse effects was observed between the different antibiotic treatments and between patients submitted to L. reuteri supplementation during and after antibiotic treatment. There was a low incidence of adverse effects in all groups of patients with sequential therapy, probably due to the presence of the L. reuteri supplementation. CONCLUSION:The sequential treatment regimen achieved a significantly higher eradication rate of H. pylori compared with standard 7-d regimen. L. reuteri supplementation could reduce the frequency and the intensity of antibiotic-associated side-effects.     

Fluoroquinolone-based protocols for eradication of Helicobacter pylori

Helicobacter pylori (H. pylori) is a widespread pathogen infecting about 40% of people living in urban areas and over 90% of people living in the developing regions of the world. H. pylori is well-documented as the main factor in the pathogenesis of peptic ulcer disease, chronic gastritis, and gastric malignancies such as cancer and mucosa-associated lymphoid tissue-lymphoma; hence, its eradication is strongly recommended. The Maastricht IV consensus, which focused on the management of H. pylori infection, set important new strategies in terms of treatment approaches, particularly with regards to first- and second-line treatment protocols and led to improved knowledge and understanding of H. pylori resistance to antibiotics. In recent years, various fluoroquinolone-based protocols, mainly including levofloxacin, have been proposed and effectively tested at all therapeutic lines for H. pylori eradication. The aim of the present paper is to review the scientific literature focused on the use of fluoroquinolones in eradicating H. pylori.