Optimized sequential therapy vs 10- and 14-d concomitant therapy for eradicating Helicobacter pylori: A randomized clinical trial

BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy,tolerability and cost.The most common sequential therapy consists of a dual therapy[proton-pump inhibitors(PPIs)and amoxicillin]for the first period(5 to 7 d),followed by a triple therapy for the second period(PPI,clarithromycin and metronidazole).PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics,hence the idea of using new generation molecules.This open-label prospective study randomized 328 patients with confirmed H.pylori infection into three groups(1:1:1):The first group received quadruple therapy consisting of twice-daily(bid)omeprazole 20 mg,amoxicillin 1 g,clarith-romycin 500 mg and metronidazole 500 mg for 10 d(QT-10),the second group received a 14 d quadruple therapy following the same regimen(QT-14),and the third group received an optimized sequential therapy consisting of bid rabe-prazole 20 mg plus amoxicillin 1 g for 7 d,followed by bid rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg for the next 7 d(OST-14).AEs were recorded throughout the study,and the H.pylori eradication rate was determined 4 to 6 wk after the end of treatment,using the 13C urea breath test.RESULTS In the intention-to-treat and per-protocol analysis,the eradication rate was higher in the OST-14 group compared to the QT-10 group:(93.5%,85.5%P=0.04)and(96.2%,89.5%P=0.03)respectively.However,there was no statist-ically significant difference in eradication rates between the OST-14 and QT-14 groups:(93.5%,91.8%P=0.34)and(96.2%,94.4%P=0.35),respectively.The overall incidence of AEs was significantly lower in the OST-14 group(P=0.01).Furthermore,OST-14 was the most cost-effective among the three groups.CONCLUSION The optimized 14-d sequential therapy is a safe and effective alternative.Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.

Effect and mechanism of Qingre Huashi decoction on drug-resistant Helicobacter pylori

BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric cancer.HP infection affects over 4.4 billion people globally,with a worldwide infection rate of up to 50%.The multidrug resistance of HP poses a serious challenge to eradication.It has been monstrated that compared to bismuth quadruple therapy,Qingre Huashi decoction(QHD)combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions;in addition,QHD directly inhibit and kill HP in vitro.METHODS In this study,12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients.In vitro,the minimum inhibitory concentration(MIC)values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining,respectively.The most robust biofilm-forming strain of HP was selected,and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation.This assessment was performed using agar dilution,E-test,killing dynamics,and transmission electron microscopy(TEM).The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation.Crystalline violet method,scanning electron microscopy,laser confocal scanning microscopy,and(p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains.The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction.Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups.RESULTS HP could form biofilms of different degrees in vitro,and the intensity of formation was associated with the drug resistance of the strain.QHD had strong bacteriostatic and bactericidal effects on HP,with MICs of 32-64 mg/mL.QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains,disrupt the biofilm structure,lower the accumulation of(p)ppGpp,decrease the expression of biofilm-related genes including LuxS,Spot,glup(HP1174),NapA,and CagE,and reduce the expression of efflux pump-related genes such as HP0605,HP0971,HP1327,and HP1489.Based on metabolomic analysis,QHD induced oxidative stress in HP,enhanced metabolism,and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate(AMP),thereby affecting HP growth,metabolism,and protein synthesis.CONCLUSION QHD exerts bacteriostatic and bactericidal effects on HP,and reduces HP drug resistance by inhibiting HP biofilm formation,destroying its biofilm structure,inhibiting the expression of biofilm-related genes and efflux pump-related genes,enhancing HP metabolism,and activating AMP in HP.

Vonoprazan-amoxicillin dual regimen with Saccharomyces boulardii as a rescue therapy for Helicobacter pylori:Current perspectives and implications

Yu et al’s study in the World Journal of Gastroenterology(2023)introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii(S.boulardii)for the rescue therapy against Helicobacter pylori(H.pylori),a pathogen responsible for peptic ulcers and gastric cancer.Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression,which is minimally affected by mealtime.Compared to proton pump inhibitors,which bind irreversibly to cysteine residues in the H+/K+-ATPase pump,Vonoprazan competes with the K+ions,prevents the ions from binding to the pump and blocks acid secretion.Concerns with increasing antibiotic resistance,effects on the gut microbiota,patient compliance,and side effects have led to the advent of a dual regimen for H.pylori.Previous studies suggested that S.boulardii plays a role in stabilizing the gut barrier which improves H.pylori eradication rate.With an acceptable safety profile,the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile,thereby strengthening the applicability in clinical settings.Nonetheless,S.boulardii comes in various formulations and dosages,warranting further exploration into the optimal dosage for supplementation in rescue therapy.Additionally,larger,randomized,double-blinded controlled trials are warranted to confirm these promising results.

Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication in Chinese population:A prospective,multicenter,randomized,two-stage study

BACKGROUND The efficacy of Vonoprazan-amoxicillin dual therapy(VAT)in the treatment of Helicobacter pylori(H.pylori)is controversial.AIM To evaluate the efficacy of VAT in the Chinese population.METHODS This prospective,multicenter,randomized,open-label,and two-stage study was conducted at 23 centers in Fujian,China(May 2021-April 2022).H.pylori-infected patients were randomized to bismuth quadruple therapy(BQT),BQT-Vonoprazan(BQT-V),seven-day VAT(VAT-7),ten-day VAT(VAT-10),and fourteen-day VAT(VAT-14)groups.The primary endpoint was the H.pylori eradication rate.The secondary endpoint was the frequency of adverse events.This study was registered with the Chinese Clinical Trial Registry,ChiCTR2100045778.RESULTS In the first stage,VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated.In the second stage,the eradication rates for BQT,VAT-10,and VA-14 were 80.2%[95%confidence interval(95%CI):71.4%-86.8%],93.2%(86.6%-96.7%),92.2%(85.3%-96.0%)in the intention-to-treat(ITT)analysis,and 80.9%(95%CI:71.7%-87.5%),94.0%(87.5%-97.2%),and 93.9%(87.4%-97.2%)in the per-protocol analysis.The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group(P=0.022 and P=0.046,respectively).The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group(25.27%and 13.73%vs 37.62%,respectively;P<0.001).CONCLUSION VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT,with a more tolerable safety profile in H.pylori-infected patients in Fujian.Huang XP et al.VAT for H.pylori eradication.

Efficacy and safety of low-dose tetracycline,amoxicillin quadruple therapy in Helicobacter pylori infection:A retrospective single center study

BACKGROUND Helicobacter pylori(H.pylori)eradication rates have declined with the rise of antibiotic-resistant strains in recent years.Although highly effective with a low prevalence of resistance,standard dose tetracycline is associated with frequent adverse events.The efficacy and safety of low-dose tetracycline as part of tetra-cycline and amoxicillin-containing bismuth quadruple therapy are not well described.AIM To compare the efficacy and safety of low-dose compared to standard dose tetracycline with combined amoxicillin-containing bismuth quadruple therapy in patients with H.pylori infection.METHODS Consecutive patients with H.pylori infection receiving tetracycline,amoxicillin,proton pump inhibitor,and bismuth for 14 days at Sir Run Run Shaw Hospital(1/2022-6/2023)were evaluated.The low-dose tetracycline group received tetracycline 500 mg twice daily(bid)while the standard dose group received 750 mg bid or 500 mg three times daily(tid).Primary endpoints were H.pylori eradication rate and treatment-related adverse events.

Role of high-dose amoxicillin dual therapy for Helicobacter pylori eradication in an Irish cohort:A prospective study

Helicobacter pylori(H.pylori)infections may cause chronic gastritis,peptic ulcer disease,gastric cancers,and other conditions outside of the gastrointestinal tract.Hence,it is important to diagnose and treat it early.H.pylori is resistant to certain drugs in traditional eradication therapy,so alternative therapy protocols are needed,such as high-dose amoxicillin dual therapy(HDADT).This article aims to comment on a recent paper by Costigan et al in the World Journal of Clinical Cases.In this study,the authors recruited 139 patients diagnosed with H.pylori,all treated with HDADT.Of these,93 were treatment-naïve and 46 had received at least one alternative treatment in the past.Four weeks after the end of the treatment,the urea breath test was administered to estimate the eradication rate.The total eradication rate was 56%(78/139),62%for the treatment-naïve arm and 43%for the previous treatment arm,thus indicating a lower success rate for the arm that had previously received a different treatment regimen.In conclusion,a therapeutic approach with first-line HDADT may potentially be a better treat-ment,but the results are not sufficient to recommend the use of this regimen in a country with high levels of dual resistance.

Non-improvement of atrophic gastritis in cases of gastric cancer after successful Helicobacter pylori eradication therapy

BACKGROUND Helicobacter pylori(H.pylori)infection is closely related to the development of gastric cancer(GC).However,GC can develop even after H.pylori eradication.Therefore,it would be extremely useful if GC could be predicted after eradication.The Kyoto classification score for gastritis(GA)is closely related to cancer risk.However,how the score for GC changes after eradication before onset is not well understood.AIM To investigate the characteristics of the progression of Kyoto classification scores for GC after H.pylori eradication.METHODS Eradication of H.pylori was confirmed in all patients using either the urea breath test or the stool antigen test.The Kyoto classification score of GC patients was evaluated by endoscopy at the time of event onset and three years earlier.In ad-dition,the modified atrophy score was evaluated and compared between the GC group and the control GA group.RESULTS In total,30 cases of early GC and 30 cases of chronic GA were evaluated.The pathology of the cancer cases was differentiated adenocarcinoma,except for one case of undifferentiated adenocarcinoma.The total score of the Kyoto classifi-cation was significantly higher in the GC group both at the time of cancer onset and three years earlier(4.97 vs 3.73,P=0.0034;4.2 vs 3.1,P=0.0035,respectively).The modified atrophy score was significantly higher in the GC group both at the time of cancer onset and three years earlier and was significantly improved only in the GA group(5.3 vs 5.3,P=0.5;3.73 vs 3.1,P=0.0475,respectively).CONCLUSION The course of the modified atrophy score is useful for predicting the onset of GC after eradication.Patients with severe atrophy after H.pylori eradication require careful monitoring.

Research Progress of Radical Treatment of Helicobacter Pylori Based on Drug Sensitivity Test as First-Line Treatment

Helicobacter pylori (HP) infection is a global problem that affects about half of the world’s population and requires sufficient attention in clinical and scientific work. Due to differences in economic and medical conditions among countries around the world, there is currently no unified treatment plan for anti-HP. In China, empirical quadruple therapy is mainly used. With the abuse of antibiotics, many patients face the problem of secondary eradication after failure, and the resistance rate of HP is gradually increasing. After eradication failure, drug sensitivity cultivation is carried out to choose sensitive antibiotics for treatment. A new strategy is currently needed to address how to improve the eradication rate of HP during the first eradication. This article aims to discuss the first-line treatment plans and research progress for eradicating HP based on drug sensitivity testing before eradication. Compared with traditional empirical therapies, treatment based on drug sensitivity results can effectively improve the eradication rate of HP, and reduce drug resistance rates, and adverse reactions, among other benefits. .

Helicobacter pylori eradication with moxifloxacin-containing therapy following failed first-line therapies in South korea

AIM: To investigate moxifloxacin-containing triple therapy as second-line treatment for Helicobacter pylori (H. pylori) infection following failed first-line treatment.

Helicobacter pylori:High dose amoxicillin does not improve primary or secondary eradication rates in an Irish cohort

BACKGROUND Helicobacter pylori(H.pylori)eradication rates have fallen globally,likely in large part due to increasing antibiotic resistance to traditional therapy.In areas of high clarithromycin and metronidazole resistance such as ours,Maastricht VI guidelines suggest high dose amoxicillin dual therapy(HDADT)can be considered,subject to evidence for local efficacy.In this study we assess efficacy of HDADT therapy for H.pylori eradication in an Irish cohort.AIM To assess the efficacy of HDADT therapy for H.pylori eradication in an Irish cohort as both first line,and subsequent therapy for patients diagnosed with H.pylori.METHODS All patients testing positive for H.pylori in a tertiary centre were treated prospectively with HDADT(amoxicillin 1 g tid and esomeprazole 40 mg bid×14 d)over a period of 8 months.Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy.A delta-over-baseline>4%was considered positive.Patient demographics and treatment outcomes were recorded,analysed and controlled for basic demographics and prior H.pylori treatment.RESULTS One hundred and ninety-eight patients were identified with H.pylori infection,10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing.In all 139 were included in the analysis,55%(n=76)were female,mean age was 46.6 years.Overall,93(67%)of patients were treatment-naïve and 46(33%)had received at least one previous course of treatment.The groups were statistically similar.Self-reported compliance with HDADT was 97%,mild side-effects occurred in 7%.There were no serious adverse drug reactions.Overall the eradication rate for our cohort was 56%(78/139).Eradication rates were worse for those with previous treatment[43%(20/46)vs 62%(58/93),P=0.0458,odds ratio=2.15].Age and Gender had no effect on eradication status.CONCLUSION Overall eradication rates with HDADT were disappointing.Despite being a simple and possibly better tolerated regime,these results do not support its routine use in a high dual resistance country.Further investigation of other regimens to achieve the>90%eradication target is needed.

Success of susceptibility-guided eradication of Helicobacter pylori in a region with high secondary clarithromycin and levofloxacin resistance rates

BACKGROUND Resistance to clarithromycin(CLA)and levofloxacin(LFX)of Helicobacter pylori(H.pylori)is increasing in severity,and successful eradication is essential.Presently,the eradication success rate has greatly declined,leaving a large number of patients with previous treatment histories.AIM To investigate secondary resistance rates,explore risk factors for antibiotic resistance,and assess the efficacy of susceptibility-guided therapy.METHODS We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April 2023.Participants underwent a string test after an overnight fast.The gastric juice was obtained and transferred to vials containing storage solution.Subsequently,DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction(qPCR).Demographic information was also analyzed as part of the study.Based on these results,the participants were administered susceptibility-guided treatment.Efficacy was compared with that of the empiric treatment group.RESULTS A total of 132 individuals tested positive for the H.pylori ureA gene by qPCR technique.CLA resistance rate reached a high level of 82.6%(n=109),LFX resistance rate was 69.7%(n=92)and dual resistance was 62.1%(n=82).Gastric symptoms[odds ratio(OR)=2.782;95%confidence interval(95%CI):1.076-7.194;P=0.035]and rural residence(OR=5.152;95%CI:1.407-18.861;P=0.013)were independent risk factors for secondary resistance to CLA and LFX,respectively.A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment,respectively.The antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5%(77/102)and 59.0%(59/411)by the intention-to-treat(ITT)analysis and 90.6%(77/85)and 70.2%(59/84)by the per-protocol(PP)analysis,respectively.The eradication rates of these two treatment strategies were significantly different in both ITT(P=0.001)and PP(P=0.012)analyses.CONCLUSION H.pylori presented high secondary resistance rates to CLA and LFX.For patients with previous treatment failures,treatments should be guided by antibiotic susceptibility tests or regional antibiotic resistance profile.

Metabolic dynamics in chronic gastritis:Examining urinary profiles post Helicobacter pylori eradication

Chronic gastritis is the persistent and insidious inflammation of the gastric lining.Helicobacter pylori(H.pylori)has been identified as the most common cause of chronic gastritis and consequently elimination of H.pylori can lead to its cure.This editorial explores the use of urinary metabolic profiles before and after eradication to identify biomarkers that can aid in prognosis and treatment.Despite providing promising insights,there are limitations such as a small sample size(17 patients),a narrow treatment period of 2 wk,and treatment heterogeneity,which raise concerns.Nevertheless,these findings have opened a gateway to enhancing the treatment and prognosis of chronic gastritis through urinary metabolomics.

Standard triple therapy for Helicobacter pylori infection in China: A meta-analysis

AIM: To assess the efficacy and safety of standard triple therapy compared with other pre-existing and new therapies in China.

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 &#x0003e; 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-1&#x003b2;). 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.

Standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori eradication

AIM: To compare the effectiveness of standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori (H. pylori ) eradication in a randomized, double-blinded, comparative clinical trial in China. METHODS: A total of 215 H. pylori -positive patients were enrolled in the study and randomly allocated into three groups: group A (n = 72) received a 10-d bismuth pectin quadruple therapy (20 mg rabeprazole bid , 1000 mg amoxicillin bid , 100 mg bismuth pectin qid , and 500 mg levofloxacin qd ); group B (n = 72) received the sequential therapy (20 mg omeprazole bid , 1000 mg amoxicillin bid , in 5 d, followed by 20 mg omeprazole bid , 500 mg tinidazole bid , 500 mg clarithromycin bid , for another 5 d); group C (n = 71) received a standard 1-wk triple therapy (20 mg omeprazole bid , 1000 mg amoxicillin bid , 500 mg clarithromycin bid ). After all these treatments, 20 mg omeprazole bid was administrated for 3 wk. H. pylori status was assessed by histology, 13C-urea breath test and rapid urease test at baseline and 4-6 wk after completion of treatment. Ulcer cicatrization was assessed by gastroscopy. χ 2 test (P < 0.05) was used to compare the eradication rates and ulcer cicatrisation rates among the three groups. RESULTS: The eradication rate was 83.33% (60/72) in group A, 88.89% (64/72) in group B, and 80.56% (58/71) in group C. The ulcer cicatrisation rate was 86.44% (51/59) in group A, 90.16% (55/61) in group B, and 84.91% (45/53) in group C. The sequential therapy yielded a higher eradication rate and ulcer cicatrisation rate than the standard triple and bismuth pectin quadruple therapies. Statistically, the eradication rate of group B was significantly different from groups A and C (P < 0.05), but the difference of ulcer cicatrisation rate and side effects was not statistically significant among the three groups (P > 0.05). The three protocols were generally well tolerated. CONCLUSION: The sequential therapy has achieved a significantly higher eradication rate, and is a more suitable first-line alternative protocol for anti-H. pylori infection compared with the standard triple and bismuth pectin quadruple therapies.

Seven-day triple therapy is a better choice for Helicobacter pylori eradication in regions with low antibiotic resistance

AIM: To investigate whether 7-d triple therapies are still valid in populations with low levels of resistance.METHODS: A total of 1106 Helicobacter pylori(H. pylori)-positive patients were divided into three groups,each of which received one type of 7-d triple therapy. Therapeutic outcomes of the patients were assessed by the 13C-urea breath test at 8 wk after treatment. The susceptibility of H. pylori to antibiotics was determined by an agar-dilution method. Data analysis was performed by χ2 tests.RESULTS: The eradication rates in groups A,B and C were 90.71%(332/366),90.46%(313/346) and 90.87%(189/208),respectively(P = 0.986). The resistance rates were 8.91% for clarithromycin,14.78% for levofloxacin and 0% for amoxicillin. The eradication rate was significantly different between clarithromycin-and levofloxacin-resistant patients(P < 0.05) in group A. Patients whose treatment failed in group A also had a higher clarithromycin resistance rate than did successive patients(P = 0.034). However,levofloxacin resistance had no obvious influence on the eradication rate. Furthermore,three main antibiotics(clarithromycin,levofloxacin and amoxicillin) had lower DID(defined daily dose per 1000 inhabitants per day) in this city.CONCLUSION: Clarithromycin resistance is the main reason for the failure of 7-d triple therapy. In populations with low levels of resistance,a 7-d triple therapy is a viable choice. The choice of therapy should not be influenced by conditions in high antibiotic resistance regions.

Helicobacter pylori:Future perspectives in therapy reflecting three decades of experience

The rising prevalence of antibiotic resistance has created a need to reassess the established Helicobacter pylori(H.pylori)eradication protocols,and to develop new ones.Various bacterial and host factors are evaluated,and their contribution to eradication failure is estimated.For a long time being considered the cornerstone eradication scheme,the standard triple therapy has been replaced with novel,more efficient regimens,namely sequential and concomitant,along with the emergence of a new design of bismuth quadruple therapy.A rescue levofloxacin based regimen has overcome the fear of therapy failure due to higher prevalence of dual resistant(clarithromycin and metronidazole)H.pylori.Culture-free and efficient susceptibility test are reestablishing the concept of tailored therapy,making eradication success close to originally desirable rates.Alleviating therapy side effects and improving patient compliance are as important as choosing appropriate eradication schemes,so various probiotic compound supplements are taken into consideration.Finally,we summarize the emerging efforts and obstacles in creating efficientH.pylori vaccine.

Furazolidone,amoxicillin,bismuth and rabeprazole quadruple rescue therapy for the eradication of Helicobacter pylori

AIM： To compare the efficacy and side effect profiles of three furazolidone and amoxicillin-based quadruple rescue therapies for the eradication of Helicobacter pylori （H pylonS. METHODS： Patients who failed in the Hpylori eradication therapy for at least one course were randomly allocated into three groups. Group A received rebaprazole 10 mg＋ amoxicillin 1 g ＋ furazolidone 100 mg, and bismuth subcitrate 220 mg, twice daily for 1 wk; group B received the same regimen of group A but for 2 wk; and group C received the same regimen of group B, but furazolidone was replaced by furazolidone 100 mg three times daily. To record the side effect profiles at the end of the treatment, Hpylori eradication was assessed with 13C-urea breath test 4 wk after therapy. RESULTS： Sixty patients were enrolled including 28 males, and 20 patients in each group. The average age of the patients was 49.2 years, ranging from 18 to 84 years. H pylori eradication rates with per-protocol analysis were 82%, 89% and 90% in the three groups, respectively. Side effects were found in 11 patients, including mild dizziness, nausea, diarrhea and increased bowel movement. None of the 11 patients needed treatment for their side effects. CONCLUSION： One- or two-week furazolidone and amoxicillin-based quadruple rescue therapy with a low dose furazolidone （100 mg bid） for the eradication of Hpylori is effective. Extending the antibiotic course to 14 d could improve the eradication rates.

Third-line rescue therapy for Helicobacter pylori infection

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

Hybrid therapy for Helicobacter pylori infection:A systemic review and meta-analysis

AIM: To compare the effectiveness of hybrid therapy with other recommended regimens using metaanalysis.METHODS: Bibliographical searches for randomized trials comparing hybrid and other therapies were performed in Pubmed, the Cochrane Library and relevant congresses up to February 2015 using the following keywords(all fields and/or me SH):("Helicobacter pylori " or "H. pylori") and("hybrid therapy" or "sequential-concomitant therapy"). metaanalyses were performed with Cochrane Review manager 5.1. The random effect model proposed by Der Simonian and Laird and the mantel-Haenszel method were used to estimate the pooled relative risk and 95%CI of the efficacy outcomes between hybrid therapy and other eradication therapies. RESULTS: Eight studies(2516 subjects) met entry criteria. The antimicrobial resistance in the study groups ranged from 6.9% to 23.5%. The mean cure rates of hybrid therapy by intention-to-treat(ITT) and perprotocol analyses were 88.5%(n = 1207; range: 80.0% to 97.4%) and 93.3%(n = 1109; range: 85.7% to99.1%), respectively. meta-analysis showed there was no significant difference in ITT eradication rate between hybrid and sequential therapy(relative risk: 1.01; 95%CI: 0.92-1.11). Subgroup analysis revealed hybrid therapy was more effective than sequential therapy in the non-Italian populations(95%CI: 1.01-1.18) and was only less effective in one, Italian population(95%CI: 0.83-0.98). There was no significant difference in eradication rate between hybrid therapy and concomitant therapy(95%CI: 0.93-1.02). No head-tohead comparisons of hybrid therapy and standard triple therapy or bismuth quadruple therapy were found. However, a multicenter, randomized trial showed that reverse hybrid therapy was superior to standard triple therapy(95.5% vs 88.6% ITT; P = 0.011).CONCLUSION: Hybrid therapy appears to be an effective, safe, and well-tolerated treatment for H. pylori infection in the era of increasing antibiotic resistance.