Proton Pump Inhibitor Triple Therapy Research Articles

Treatment of Helicobacter pylori with potassium competitive acid blockers: A systematic review and meta-analysis.

Helicobacter pylori (H. pylori) infects over half the global population, causing gastrointestinal diseases like dyspepsia, gastritis, duodenitis, peptic ulcers, G-MALT lymphoma, and gastric adenocarcinoma. Eradicating H. pylori is crucial for treating and preventing these conditions. While conventional proton pump inhibitor (PPI)-based triple therapy is effective, there's growing interest in longer acid suppression therapies. Potassium competitive acid blocker (P-CAB) triple and dual therapy are new regimens for H. pylori eradication. Initially used in Asian populations, vonoprazan (VPZ) has been recently Food and Drug Administration-approved for H. pylori eradication. To assess the efficacy of regimens containing P-CABs in eradicating H. pylori infection. This study, following PRISMA 2020 guidelines, conducted a systematic review and meta-analysis by searching MEDLINE and Scopus libraries for randomized clinical trials (RCTs) or observational studies with the following command: [("Helicobacter pylori" OR "H pylori") AND ("Treatment" OR "Therapy" OR "Eradication") AND ("Vonaprazan" OR "Potassium-Competitive Acid Blocker" OR "P-CAB" OR "PCAB" OR "Revaprazan" OR "Linaprazan" OR "Soraprazan" OR "Tegoprazan")]. Studies comparing the efficacy of P-CABs-based treatment to classical PPIs in eradicating H. pylori were included. Exclusion criteria included case reports, case series, unpublished trials, or conference abstracts. Data variables encompassed age, diagnosis method, sample sizes, study duration, intervention and control, and H. pylori eradication method were gathered by two independent reviewers. Meta-analysis was performed in R software, and forest plots were generated. A total of 256 references were initially retrieved through the search command. Ultimately, fifteen studies (7 RCTs, 7 retrospective observational studies, and 1 comparative unique study) were included, comparing P-CAB triple therapy to PPI triple therapy. The intention-to-treat analysis involved 8049 patients, with 4471 in the P-CAB intervention group and 3578 in the PPI control group across these studies. The analysis revealed a significant difference in H. pylori eradication between VPZ triple therapy and PPI triple therapy in both RCTs and observational studies [risk ratio (RR) = 1.17, 95% confidence interval (CI): 1.11-1.22, P < 0.0001] and (RR = 1.13, 95%CI: 1.09-1.17, P < 0.0001], respectively. However, no significant difference was found between tegoprazan (TPZ) triple therapy and PPI triple therapy in both RCTs and observational studies (RR = 1.04, 95%CI: 0.93-1.16, P = 0.5) and (RR = 1.03, 95%CI: 0.97-1.10, P = 0.3), respectively. VPZ-based triple therapy outperformed conventional PPI-based triple therapy in eradicating H. pylori, positioning it as a highly effective first-line regimen. Additionally, TPZ-based triple therapy was non-inferior to classical PPI triple therapy.

Treatment of Helicobacter pylori infection 14-day concomitant quadruple therapy versus triple therapy: A parallel double-blind randomized controlled trial.

Successful Helicobacter pylori (Hp) eradication with the traditional 7-day course of proton pump inhibitor triple therapy is declining. Prolonging therapy to 14 days is associated with better eradication rates. Most learned societies recommend concomitant quadruple therapy (QC) as a first-line alternative therapy for this bacterial infection. The aim of this study is to compare the efficacy and safety of triple therapy (TT) and QC for the eradication of Hp infection. A parallel double-blind randomized controlled trial was conducted. The diagnosis of Hp infection was made by pathological examination of gastric biopsies. Patients were randomly assigned to two treatment groups: either QC (esomeprazole 80 mg, amoxicillin 2000 mg, clarithromycin 1000 mg, and metronidazole 1000 mg daily) or triple therapy (esomeprazole 80 mg, amoxicillin 2000 mg, and clarithromycin 1000 mg daily in divided doses) for 14 days. The efficacy of the treatment is defined by Hp eradication attested by a negative breath test performed 6 weeks after the completion of treatment. Treatment outcomes were compared using the chi-square test, while binary logistic regression identified predictors of treatment failure. Ninety-two patients were included. Forty-two patients belonged to the QC group and 50 to the TT group. No significant difference was noted between the two groups concerning the rate of Hp eradication either by intention to treat (81% vs. 72% respectively, p = 0.31) or per protocol (81.6% vs. 76.1% respectively, p = 0.54). Likewise, there was no difference between the two groups in terms of tolerance to treatment (59.5% for QC vs. 58% for TT, p = 0.88). No factor has been associated with treatment failure. There was no significant difference in the rate of HP eradication between the QC and the 14-day triple therapy. Neither regimen should be used topically because of their low eradication rates.

Study of Acid-related Disorders: Real-world Physician and Patient Perspectives on Burden of Helicobacter pylori Infection

<h3>Background and Aims</h3> <i>Helicobacter pylori</i> eradication rates have declined as antibiotic resistance rates have increased. In addition, adherence to treatment guidelines is suboptimal. It is therefore important that contemporary, real-world evidence of diagnostic and treatment patterns is explored and compared with evidence-based guidelines. The Study of Acid-Related Disorders investigated unmet needs among patients with <i>H pylori</i> infection and past or current dyspepsia. <h3>Methods</h3> Gastroenterologists (GIs) and family physicians (FPs) or general practitioners (GPs) treating patients with <i>H pylori</i> infection and past or current dyspepsia completed a physician survey and invited patients to complete a patient survey; data were also extracted from the medical records of enrolled patients. <h3>Results</h3> Two hundred fifty-one physicians and 77 patients were enrolled. A total of 19.5% of patients were diagnosed by serology, whereas the urea breath test was used by 6.5% of GIs and 50.0% of FPs or GPs. A total of 68.6% of GIs and 79.8% of FPs or GPs selected clarithromycin, amoxicillin, and proton pump inhibitor triple therapy as their ideal first-line treatment. Physicians reported that 52.9% of patients experienced dyspepsia daily. A total of 46.8% of patients believed that complete resolution of dyspepsia would indicate effective treatment. As their treatment goal, 69.3% of physicians selected improvement in overall symptoms, whereas 92.2% of patients specified improvement in dyspepsia. Only 28.7% of physicians were satisfied with current treatment options. A total of 59.7% of patients took all of their prescribed medicine(s). A total of 59.7% of patients would prefer to take fewer pills; 45.5% would prefer convenience packs. <h3>Conclusion</h3> This study reveals a lack of adherence to current <i>H pylori</i> guidelines for diagnosis, testing, and treatment. New treatment options that are more efficacious and simpler for patients to adhere to are needed.

Favorable outcomes of rescue second- or third-line culture-based Helicobacter pylori eradication treatment in areas of high antimicrobial resistance.

Failure of second or third-line eradication treatment against Helicobacter pylori (H.pylori) is principally caused by antimicrobial resistance and reduced treatment adherence. To evaluate the efficacy and safety of culture-based rescue eradication treatments in patients who have previously experienced failed eradication treatment. Patients who had persistent H.pylori infection following at least one eradication treatment were recommended to undergo culture analysis to determine the minimal inhibitory concentrations of various antimicrobials via endoscopic resection. Consenting patients were assigned one of four therapeutic treatments based on an algorithm determined by antimicrobial resistance. These treatments consisted of 7 or 14-day administration of clarithromycin-containing proton pump inhibitor (PPI) triple therapy; esomeprazole, moxifloxacin, and amoxicillin (MEA) therapy; esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapy; or lansoprazole, rifabutin, and amoxicillin (RLA) therapy. Eradication efficacy, adherence, and adverse events were assessed aside clinical outcomes. A total of 132 patients were enrolled, with 84 patients completing the study. The overall resistance rates to amoxicillin, clarithromycin, metronidazole, and moxifloxacin were 13.1%, 83.3%, 47.6%, and 71.4%, respectively. The patients were allocated to the PPI triple (n=11), MEA (n=15), quadruple (n=53), or RLA triple (n=5) therapy group. The eradication rates in the intention-to-treat and per-protocol analyses were 90.5% (76 of 84 patients) and 93.8% (76 of 81 patients), respectively. Nausea was the most frequent adverse event (25.0%). As a rescue therapy, culture-based susceptibility-guided eradication treatment was both effective and safe, even for patients exhibiting high antimicrobial resistance.

The status and progress of first-line treatment against Helicobacter pylori infection: a review.

Helicobacter pylori (HP) is a major causative agent of chronic gastritis and peptic ulcer. HP is also engaged in the development of gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. It is an important pathogenic factor in various other systemic diseases, such as vitamin B12 deficiency, iron deficiency, and idiopathic thrombocytopenia. The current consensus is that unless there is a special reason, eradication therapy should be implemented whenever HP infection is found, and it is ideally successful the first time. International guidelines recommend that under certain conditions, treatment should be personalized based on drug susceptibility testing. However, drug susceptibility testing is often not available because it is expensive, time-consuming, and difficult to obtain living tissue. Each region has separately formulated guidelines or consensuses on empirical therapy. Owing to an increasing drug resistance rate in various places, the eradication rate of proton pump inhibitor (PPI) triple therapy and sequential therapy has been affected. These regimens are rarely used; the PPI triple especially has been abandoned in most areas. Currently, radical treatment regimens for HP involve bismuth-containing quadruple therapy and concomitant therapy. However, quadruple therapy has its own limitations, such as complex drug administration. To improve the effectiveness, safety, and compliance, many clinical studies have proposed useful modified regimens, which mainly include the modified bismuth-containing quadruple regimen, high-dose dual therapy, and vonoprazan-containing regimens. Studies have shown that these emerging regimens have acceptable eradication rates and safety, and are expected to become first-line treatments in empirical therapy. However, the problem of decline in the eradication rate caused by drug resistance has not been fundamentally solved. This review not only summarizes the effectiveness of mainstream regimens in the first-line treatment of HP infection with the currently increasing antibiotic resistance rates, but also summarizes the effectiveness and safety of various emerging treatment regimens.

Effects of Jinghua Weikang capsule combined with triple therapy in the treatment of Helicobacter pylori positive verrucous gastritis

Objective To explore the clinical effect of Jinghua Weikang capsule combined with proton pump inhibitor(PPI) triple therapy in the treatment of Helicobacter pylori(Hp) positive verrucous gastritis. Methods From January 2013 to March 2017, 120 patients with Hp positive verrucous gastritis who admitted to the Affiliated Hospital of Shanxi Datong University were selected, and they were randomly divided into control group and observation group, with 60 cases in each group.The control group was treated with PPI triple therapy, and on the basis, the observation group was treated with Jinghua Weikang capsule.The curative effects were compared between the two groups, and the improvement of symptoms and signs were assessed.The Hp eradication rate was statistically analyzed, and the adverse drug reactions were recorded.All patients were followed up for 6 months, and the recurrence rate in the two groups after drug withdrawal was statistically analyzed. Results The total effective rate of the observation group was higher than that of the control group(95.00% vs.80.00%)(χ2=6.171, P 0.05). The recurrence rates of Hp infection in the observation group at 3 months and 6 months after drug withdrawal were lower than those in the control group(6.67%, 8.33% vs.20.00%, 23.33%)(χ2=4.615, 5.065, all P<0.05). Conclusion Jinghua Weikang capsule combined with PPI triple therapy can improve the curative effect of Hp positive verrucous gastritis, improve symptom scores, the Hp eradication rate and reduce the recurrence rate after drug withdrawal, with high safety. Key words: Gastritis; Helicobacter pylori; Jinghua Weikang Jiaowan; Drug therapy, combination

Ten-day high-dose proton pump inhibitor triple therapy versus sequential therapy for Helicobacter pylori eradication.

Eradication rates of Helicobacter pylori following standard triple therapy are declining worldwide, but high-dose proton pump inhibitor-based triple therapy (HD-PPI-TT) and sequential therapy (ST) have demonstrated higher cure rates. We aimed to compare the efficacy and tolerability of HD-PPI-TT and ST in H.pylori-associated functional dyspepsia (FD). One hundred and twenty H.pylori-associated functional dyspepsia patients were randomized to receive 10-day HD-PPI-TT (60mg lansoprazole/500mg clarithromycin/1g amoxicillin, each administered twice daily for 10days) or 10-day ST (30mg lansoprazole/1g amoxicillin, each administered twice daily for 5days followed by 30mg lansoprazole/500mg clarithromycin/400mg metronidazole, each administered twice daily for 5days). H.pylori status was determined in post-treatment week 4 by 14 C-urea breath test. Eradication and antibiotic resistance rates, dyspeptic symptoms, drug compliance, and adverse effects were compared. Intention-to-treat eradication rates were similar in the ST and HD-PPI-TT groups (85% vs. 80%; P=0.47). However, the eradication rate was significantly higher following ST compared with HD-PPI-TT in per protocol analysis (94.4% vs. 81.4%; P=0.035). ST achieved higher cure rates than HD-PPI-TT in clarithromycin-resistant H.pylori strains (100% vs. 33.3%; P=0.02). Treatment compliance was similar in the HD-PPI-TT and ST groups, although nausea and dizziness were more common in the ST group. Sequential therapy achieved better H.pylori eradication than HD-PPI-TT in patients with FD. However, the eradication rate for ST fell from 94.4% in per protocol to 85% in intention-to-treat analysis. Adverse effects might result in poorer compliance and compromise actual ST efficacy (ClinicalTrials.gov: NCT01888237).

Luminal Clinical

<b>Luminal Clinical</b>

A comparison between 15-day sequential, 10-day sequential and proton pump inhibitor-based triple therapy for Helicobacter pylori infection in Korea

Objective. The eradication rate of 10-day sequential therapy for Helicobacter pylori (H. pylori) infection was not satisfactory in Korea, probably due to antibiotic resistance. To compare the treatment efficacy of 15-day and 10-day sequential therapy of conventional 7-day proton pump inhibitor (PPI) triple therapy for the treatment of H. pylori infection. Methods. A total of 332 patients with H. pylori infection were randomly assigned to receive either 7-day PPI triple therapy, 10-day sequential therapy or 15-day sequential therapy. Eradication rate, drug compliance, and adverse events were compared among the three regimens. Results. The eradication rates by intention-to-treat analysis were 64.3% (95% CI: 55.5–73.2; 74 of 115 patients), 72.1% (95% CI: 63.6–80.5; 80 of 111 patients), and 80.2% (95% CI: 72.5–87.9; 85 of 106 patients) in the 7-day PPI triple, 10-day and 15-day sequential therapy groups, respectively (p = 0.032). The eradication rates by per-protocol analysis were 68.5% (95% CI: 59.6–77.4; 74 of 108 patients), 78.4% (95% CI: 70.3–86.5; 80 of 102 patients), and 89.5% (95% CI: 83.2–95.8; 85 of 95 patients) in the 7-day PPI triple, 10-day and 15-day sequential therapy groups, respectively (p = 0.001). There were no statistically significant differences between the three eradication therapy groups in regard to drug compliance and adverse events. Conclusion. The 15-day sequential therapy demonstrated improved eradication efficacy compared with 7-day PPI triple and 10-day sequential therapy in Korea.

Optimum duration of regimens forHelicobacter pylorieradication

Optimum duration of regimens for<i>Helicobacter pylori</i>eradication

Improved Efficacy of Proton Pump Inhibitor – Amoxicillin – Clarithromycin Triple Therapy for Helicobacter pylori Eradication in Low Clarithromycin Resistance Areas or for Tailored Therapy

Standard triple therapy for Helicobacter pylori eradication is no longer effective as an empiric choice in most areas. Even in low clarithromycin resistance areas, results ≥95% are infrequently achieved. This study was designed to search for a version of standard triple therapy for use low prevalence areas or as tailored therapy that is highly effective irrespective of CYP2C19 genotype. Two prospective pilot single center studies were performed in Thailand. H.pylori-infected subjects were randomized to 7- or 14-day regimens using a high-dose proton pump inhibitor (PPI) triple therapy consisting of lansoprazole (60mg) twice daily, amoxicillin 1g twice daily, and long-acting clarithromycin MR 1g once daily. H.pylori was defined as positive H.pylori culture; or two positive tests (rapid urease test and histology); CYP2C19 genotyping was performed. H.pylori eradication was evaluated by (13) C-UBT 4 or more weeks after treatment. Hundred and ten subjects were enrolled (55 each to the 7- and 14-day regimens). Antibiotic susceptibility testing (25 strains) showed 40% metronidazole resistance but no clarithromycin resistance. CYP2C19 genotyping (64 subjects) revealed 56.3% rapid metabolizer, 29.7% intermediate metabolizer, and 14% poor metabolizer. The eradication rate with the 14-day regimen was 100% (95% CI=93.5-100%) and 92.7% (95% CI=82-97%) with the 7-day regimen. The difference was related to improved eradication at 14days in rapid metabolizers (i.e. 100 vs 88.2%). Triple therapy using a 14-day high-dose PPI and long-acting clarithromycin provided an excellent cure rate (100%) regardless of the CYP2C19 genotype.

Prolonged Treatment Duration is Required for SuccessfulHelicobacter pyloriEradication with Proton Pump Inhibitor Triple Therapy in Canada

Traditional seven-day proton pump inhibitor triple therapy for Helicobacter pylori eradication has recently shown disappointing results outside of Canada. Prolonging therapy may be associated with poorer compliance and, hence, may not have a better outcome in a real-world setting. To compare the outcomes of seven- and 14-day triple therapy for first-line treatment of H pylori infection in an effectiveness setting in Canada. A total of 314 consecutive treatment-naive, adult H pylori-infected patients were allocated to either a seven- or 14-day triple therapy regimen, with a subgroup of 172 consecutive patients quasi-randomized to treatment according to date of visit. Eradication was confirmed using either urea breath test or gastric biopsies. Analysis was by intention to treat. Eradication was achieved in a higher proportion of patients who underwent 14-day versus seven-day treatment regimens (overall: 85% versus 70% [P≤0.001]; subgroup: 83% versus 64% [P≤0.01]). Although successful eradication was also associated with older age and a diagnosis of ulcer disease, multivariate analysis revealed only longer treatment duration and lack of yogurt ingestion as independent predictors of successful eradication. There was a trend toward reduced success in the latter years of the study. Side effects were similar in both groups and were not prevented by yogurt ingestion. The currently recommended duration of proton pump inhibitor triple therapy in Canada should be increased from seven to 14 days, the latter having achieved an excellent result in this particular real-world setting. Yogurt added no benefit. Further study is required to compare 10-day with 14-day treatment regimens.

Should quinolones come first in Helicobacter pylori therapy?

New generations of fluoroquinolones, like levofloxacin and moxifloxacin, exhibit a broad-spectrum activity against Gram-positive and Gram-negative bacteria, and have been successfully introduced into the treatment of Helicobacter pylori infection. Based on a large body of evidence, current guidelines recommend the use of levofloxacin- or moxifloxacin-containing proton-pump inhibitor (PPI) triple therapies in second-line or rescue treatment of H. pylori infection. The efficacy of standard PPI triple therapies has substantially declined during the last decade, mainly due to increasing resistance against the key antibiotics clarithromycin and metronidazole. Therefore, alternative strategies for first-line therapy of H. pylori infection have been evaluated in a considerable number of clinical trials including sequential regimens, nonbismuth quadruple regimens, and quinolone-containing PPI triple therapy regimens. The aim of this paper is to summarize the current body of evidence of levofloxacin- and moxifloxacin-containing regimens in first-line treatment of H. pylori infection, and to discuss the risks and benefits of these strategies in the light of increasing resistance of H. pylori to quinolones.

Quadruple Therapy Using a 3-in-1 Capsule of Bismuth Subcitrate Potassium, Metronidazole, and Tetracycline with Omeprazole Compared to Triple Therapy for the Eradication of Helicobacter pylori: 2010 Presidential Poster

Purpose: Although proton pump inhibitor triple therapy is recommended as first line treatment of H. pylori, eradication rates <80% have been recently reported. Bismuth containing quadruple therapy is an alternative. The efficacy of these 2 approaches was evaluated by re-analyzing 2 randomized controlled trials (RCTs). Methods: One N. American RCT comparing omeprazole plus a 3-in-1 capsule of bismuth subcitrate potassium, metronidazole, and tetracycline (OBTM) vs. omeprazole, amoxicillin and clarithromycin (OAC) each given for 10 days was combined with a European RCT comparing OBTM (10 days) vs. OAC (7 days). Both RCTs evaluated therapy in patients with upper GI symptoms, positive 13C urea breath test (UBT), a rapid urease test with at least 1 positive test from histology and culture. H. pylori eradication was confirmed by 2 negative UBTs 6 and 10 weeks post therapy. The impact of sex, age, race, presence of peptic ulcer disease (PUD), duration of OAC therapy, and pretreatment H. pylori clarithromycin and metronidazole resistance was evaluated on efficacy in univariate and multivariate analyses. All data were analyzed on an intention to treat basis. Results: 299 patients were enrolled in the N. American RCT with eradication rates in OBMT arm of 126/147 (86%; 95% CI=79%-91%) and 122/152 (80%; 95% CI=73%-86%) in OAC arm. 440 patients were enrolled in the European RCT with eradication rates of 174/218 (80%; 95% CI=74%-85%) with 10d OBTM and 123/222 (55%; 95% CI=49%-62%) with 7d OAC. There were no predictors of treatment failure in OBTM arms in univariate or multivariate analysis including H. pylori metronidazole resistant strains (81% versus 86%, p=0.23). OAC was less successful in patients without PUD vs. those with PUD (eradication rate 60% vs. 77% respectively; p=0.003), in those taking 7d vs. 10d of therapy (80% vs. 55%; p<0.0001) and in clarithromycin resistant strains (12% vs. 78%, p<0.0001). These factors remained significant in a logistic regression model adjusting for all factors outlined above. In a logistic regression model combining OBTM and OAC groups adjusting for all factors plus an interaction term for clarithromycin resistance and treatment regimen, clarithromycin resistance (p=0.004) was an independent predictor of treatment failure whereas therapy with OBTM was an independent predictor of treatment success (p=0.003). Conclusion: OBTM appears less susceptible to influence of H. pylori resistance to antibiotics and other factors in determining efficacy and overall may be a better first line choice in the treatment of H. pylori infection. Disclosure: Dr Moayyedi, Advisory Board Member, Axcan Pharma; Dr Bazzolo, Advisory Board Member, Axcan Pharma; Prof Megraud, Advisory Board Member and Dr Giguere, Employee, Axcan Pharma. This research was supported by an industry grant from Axcan Pharma.

Treatment of Helicobacter pylori infection: The past and the future

0953-6205/$ – see front matter © 2010 Euro doi:10.1016/j.ejim.2010.07.009 Helicobacter pylori (H. pylori) is a worldwide infection that affects millions of people. This infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After more than 20 years of experience inH. pylori treatment, however, the ideal regimen to treat this infection has still to be found [1,2]. Themost recommended treatment for the eradication of H. pylori, in all international guidelines, is the so called standard or proton pump inhibitor (PPI) triple therapy, which includes the combination of two antibiotics (clarithromycin plus amoxicillin or metronidazole) with a PPI for at least 7 days [3,4]. However, H. pylori eradication rates with standard triple therapy have fallen from initial heights of N90% to 75–80% in some areas [5–9]. As an example, two recent double-blind, U.S. multicenter studies both found disappointingly low eradication rates with standard therapy: 77% [10,11]. Furthermore, two meta-analyses including more than 53,000 patients showed that the cure rate is, at present, below 80% [12,13]. In summary, eradication rates in most western countries have declined to unacceptable levels [2,14], probably due to increased resistance to antibiotics. In particular, antibiotic resistance to clarithromycin has been identified as one of themajor factors affecting our ability to cureH. pylori infection, and the rate of resistance to this antibiotic seems to be increasing in many geographical areas [15]. The ethics of continued use of standard triple therapy has recently been questioned and the use of alternative therapy has been recommended in its place [16]. Therefore, new strategies in order to improve first-line treatment are still urgently needed. Attempts to increase the duration of triple therapy and therefore prolong exposure to antibiotics have achieved controversial results, but, in general, have

Efficacy of 1‐week proton pump inhibitor triple therapy as first‐line Helicobacter pylori eradication regime in Asian patients: Is it still effective 10 years on?

To re-examine the efficacy and tolerability of 1-week proton pump inhibitor triple therapy as a first-line Helicobacter pylori (H. pylori) eradication therapy. Consecutive participants with a positive rapid urease test during an outpatient upper endoscopy were included. All participants were given pantoprazole 40 mg b.i.d., amoxycillin 1 g b.i.d. and clarithromycin 500 mg b.i.d. for 1 week. They were asked to return after 1 week to report any side effects related to the medications and to check for compliance. Successful eradication was defined by negative (13)C-urea breath test at least 4 weeks after the completion of therapy. A total of 191 patients were recruited into the study, of whom 81 were male (42.4%) and 110 female (57.6%), with a mean age of 55.6 (range 21-88) years. Overall 26 patients (13.6%) defaulted follow up and five patients were not compliant (taking less than 85%) with the medications. Per-protocol and intention-to-treat eradication rates were 84.4% (95% CI: 78.6-89.9%) and 71.2% (95% CI: 64.5-77.6%), respectively. Overall 68 participants (42.5%) reported no side effects, followed by 58 (36.3%) with a taste disturbance, 16 (10.0%) with epigastric pain, 15 (9.4%) with diarrhea, 13 (8.1%) with nausea or vomiting, 12 (7.5%) with loss of appetite, nine (5.6%) with dizziness and two (1.3%) with an allergic skin rash, none of which was severe. The current regime using pantoprazole, amoxycillin and clarithromycin is highly tolerable and effective and should continue to be recommended as a first-line therapy for H. pylori eradication in our setting.

Bismuth Salts in the Treatment of Helicobacter pylori Infection in Children

Delghani et al. [1] evaluated the efficacy of three different regimens for eradication of Helicobacter pylori (H. pylori) infection in children. The authors concluded that quadruple therapy containing bismuth yields better results and can be used as first-line of therapy. The study is both well designed and well managed, and highlights the need for novel therapies in children with H. pylori infection. Here are some important points of the study that should be discussed. The study group was composed of 120 children with a mean age of 12 ± 4 years (range 2–18 years). H. pylori eradication was assessed with urea breath test (UBT). The utility of UBT in children over 6 years of age was confirmed by numerous studies. The sensitivity and specificity for children in this group were found to be 100 and 98% respectively, with positive predictive value (PPV) and negative predictive values (NPV) of 98 and 100% respectively. In young children, however, false-positive results compromise the accuracy of the test. For children under the age of 6 years, specificity was determined to be 88% and PPV 69% [2]. The accuracy of UBT can be improved by increasing delta over baseline (DOB) cut-off values; however, the false-positive rate remains high [2, 3]. It would be better to provide brief methodologic data regarding UBT including information at least about cut-off values and whether values are adjusted for age. The authors reported the eradication rate with quadruple therapy with bismuth 91.8% compared to 82.1 and 80.5% with current triple therapies containing clarithromycin in the second group and metronidazole in third group, respectively. The authors suggested quadruple therapy as the first-line of therapy for the eradication of H. pylori infection in children in their geographic area. Treatment of H. pylori infection in children with protocols containing bismuth compounds have been reported with variable success [4–7]. In a recent report of pooled data [8], bismuth triple therapies were found to be more efficacious than proton pump inhibitor triple therapies (77 vs. 64%) as a first-line treatment. Indeed, the eradication rate is better with quadruple therapy in the present study, but not sufficiently high to suggest it as a first-line therapy (p = 0.33). Secondly, bismuth compounds are major drugs of rescue regimens after H. pylori treatment failure. The most important cause of treatment failure is drug resistance. In this case, it is fairly logical to reserve bismuth compounds as a second-line option to decrease the risk of drug resistance. Although the use of bismuth compounds has been reported in children [8], they still require approval to use. Therefore, the use of bismuth compounds in children may be of ethical concern. In adults, it has recently been suggested that fluoroquinolone-based rescue therapies constitute an encouraging second-line strategy, representing an alternative to quadruple therapy with efficacy, simplicity, and safety [9–11]. Although pediatric data is limited, fluoroquinolone-based therapies can be tried as rescue therapy in children over the age of 8 [12]. Lastly, compliance is an important determinant of treatment success. Multiple drug use is an important risk factor and therefore compliance is expected to be low with quadruple therapy. In conclusion, it is still too early to suggest quadruple therapy containing bismuth compounds as a first-line option in children with H. pylori infection. Moreover, we need further comparable studies in order to determine the case for quadruple therapies containing bismuth compounds as a second-line option. S. Gokce (&) Pediatric Gastroenterology, Hepatology and Nutrition, Dr. Sami Ulus Children’s Hospital, Ankara, Turkey e-mail: drgokce0007@yahoo.com

Sequential Therapy for Eradication of Helicobacter pylori: A New Guiding Light or a False Dawn?

Helicobacter pylori-related diseases are a major global problem, and currently recommended regimens are achieving disappointing eradication rates. Trials of sequential therapy have suggested that it is superior to standard proton pump inhibitor (PPI)-based triple therapy. Gatta et al. report a rigorous systematic review that identified 13 trials evaluating 3,271 patients. Their data suggest that the sequential therapy achieves a 12% better absolute eradication rate than the standard PPI triple therapy. There is no evidence of publication bias or other small study effects. The quality of all but one of the studies, however, is poor; therefore, this limits the confidence that can be placed in these data. Most of the studies were conducted in Italy, and there is evidence that the efficacy of sequential therapy in Asia is more disappointing, emphasizing the need to study this regimen in North America and other settings. Sequential therapy is not ready for prime time, but it is a promising approach that merits further study.

Sequential and Concomitant Therapy With Four Drugs Is Equally Effective for Eradication of H pylori Infection

Sequential therapy with a proton pump inhibitor (PPI) and amoxicillin followed by a PPI, clarithromycin, and an imidazole agent reportedly have a better rate of curing Helicobacter pylori infection than PPI, amoxicillin, and clarithromycin triple therapy. The concomitant administration of these 4 drugs (concomitant therapy) is also an effective treatment strategy. We compared the efficacies of sequential and concomitant therapy and analyzed the effects of antibiotic resistance in patients with H pylori infection. In a randomized trial of 232 H pylori-infected patients from 3 hospitals in Kaohsiung, Taiwan, patients were given 10 days of sequential (n = 115) or concomitant (n = 117) therapy. H pylori status was confirmed by endoscopy or urea breath test. Intention-to-treat analysis demonstrated similar eradication rates for sequential (92.3%; 95% confidence interval [CI], 87.5%-97.1%) and concomitant therapy (93.0%; 95% CI, 88.3%-97.7%)(P = .83). Per-protocol eradication results were similar for sequential (93.1%; 95% CI, 90.7%-95.5%) and concomitant therapy (93.0%; 95% CI, 88.3%-97.7%) (P = .99). Univariate analysis showed that compliance and resistance to clarithromycin were independent determinants of eradication. Dual resistance did not influence the level of eradication in the concomitant group, but significantly affected that of the sequential therapy group. Clarithromycin resistance was less frequent than expected. Sequential or concomitant therapy with a PPI, amoxicillin, clarithromycin, and an imidazole agent are equally effective and safe for eradication of H pylori infection. Resistance to clarithromycin, compliance, and adverse events reduced the level of eradication. Concomitant therapy may be more suitable for patients with dual resistance to antibiotics.

Variables Influencing Outcome of Helicobacter pylori Eradication Therapy in South China

Therapy combining a proton pump inhibitor (PPI), clarithromycin and either amoxicillin or metronidazole is widely recommended for first-line treatment for Helicobacter pylori infection. The purpose of this study was to examine the outcomes of PPI-containing triple therapy and identify factors influencing the cure rate of H. pylori infection in South China. H. pylori positive patients with different occupations from 25 hospitals in five provinces of South China were enrolled. They received a PPI, metronidazole and amoxicillin triple therapy for a week. H. pylori eradication was evaluated by (13)C-urea breath test 4 weeks after therapy. Association between H. pylori eradication with occupation, gender, age, educational level, and protocol compliance was evaluated by Logistic regression. Six hundred and seventy-five were enrolled. The intention-to-treat and per-protocol analyses showed overall cure rates of 60% (95% CI = 56.3-63.7%) and 64.5% (95% CI = 60.7-68.3%), respectively. Multivariate logistic regression showed that occupation, gender and protocol compliance were positively associated with the eradication rate (p < .01). The cure rate for those who took 80% or more of the prescribed drugs was 64.5% (95% CI = 60.7-68.3%) versus 14.6% (95% CI = 6-29%, p < .001) for those who took less. Lower eradication rates were also observed in farmers and women. The eradication rate with a PPI, metronidazole and amoxicillin triple therapy was unacceptably low in South China. These results suggest that studies of the eradication of H. pylori infection in China must take into account antibiotic resistance as well as patient occupation, gender, and protocol compliance. Gastric cancer and peptic ulcer disease are both important in China making methods to effectively and efficiently eradicate H. pylori a priority.