Classical Triple Therapy Research Articles

The significance of chronic hyperglycemia for the reduced efficacy of eradication therapy in patients with type 2 diabetes mellitus and for Helicobacter pylori survival

Aim: This study aims to determine the significance of chronic hyperglycemia for the reduced efficacy of eradication therapy in patients with type 2 diabetes mellitus (T2DM) and Helicobacter pylori (H. pylori)-associated upper gastrointestinal tract pathology as well as for H. pylori survival. Methods: A prospective randomized study with the participation of 180 patients (87 men and 93 women) with H. pylori-associated upper gastrointestinal pathology was carried out. Ninety of these patients were with T2DM and 90 were without diabetes mellitus (DM). The patients were divided into 4 groups of 45 patients: the group 1 included non-diabetic patients treated with the classical triple eradication scheme; the group 2 included patients with T2DM treated with the classical triple eradication scheme; the group 3 included non-diabetic patients treated with bismuth quadro-therapy; the group 4 included patients with T2DM treated with bismuth quadro-therapy. The presence of H. pylori and evaluation of eradication efficacy was carried out using the Helix breath test. Results: The effectiveness of 1st line anti-Helicobacter therapy was higher (88.2%) in patients without diabetes in comparison with the group of patients with concomitant T2DM (74.7%). The efficacy of classical triple eradication therapy in patients with concomitant T2DM was 69.1%, and quadro-therapy was 80.5%. There was significantly lower effectiveness (P < 0.017) of eradication therapy in patients with T2DM and glycated hemoglobin (HbA1c) level ≥ 7.0% as compared with the group of patients in whom the target (≤ 6.5%) level of HbA1c was achieved. Conclusions: Chronic hyperglycemia has a favorable effect on the viability of H. pylori bacteria in patients with T2DM. A hypothesis explaining the reduced efficacy of eradication therapy in patients with hyperglycemia has been proposed.

Antibiotic Susceptibility and Clarithromycin Resistance Determinants in Helicobacter pylori in the Northeast of Spain: A One-Year Prospective Study.

Helicobacter pylori is one of the most widespread infections, and it is reaching alarming resistance levels worldwide. The recommended first-line empirical treatment differs according to the local rate of clarithromycin resistance. Macrolide resistance is mainly associated with three point mutations in the 23S rRNA gene. The aim of this study was to describe the antibiotic susceptibility of H. pylori in our healthcare area and the main mechanisms involved in clarithromycin resistance. Gastric biopsies (n = 641) were collected and cultured in a one-year prospective study. Antibiotic susceptibility testing was performed by gradient diffusion. A multiplex real-time PCR test (AllplexTMH.pylori & ClariR Assay, Seegene) was used to detect the most frequent mutations associated with clarithromycin resistance. Overall, 141 isolates were available for antibiotic susceptibility testing. The highest resistance rates were detected in metronidazole and levofloxacin. The rate of clarithromycin resistance was 12.1%, and the associated mutations were A2143G and A2142G. More than half of the clarithromycin-resistant isolates presented high MIC values (>256 mg/L). Tetracycline resistance was not detected, suggesting that therapies that contain tetracycline could be a suitable option. The low clarithromycin resistance rate coupled with the high rates of metronidazole resistance may support the recovery of the classical triple therapy in our healthcare area.

The effectiveness of eradication therapy of the 1st line of Helicobacter pylori infection in patients with type 2 diabetes mellitus

Evaluation of the efficacy and safety of eradication therapy of infection Helicobacter pylori in patients with H. pylori- associated pathology of the upper gastrointestinal tract and concomitant type 2 diabetes mellitus (DM). The prospective randomized study involving 180 patients (87 men and 93 women) with H. pylori- associated pathology of the upper gastrointestinal tract was carried out. The patients were divided into four groups of 45 people: 1 patients without diabetes who received the classic triple eradication therapy; 2 patients with type 2 DM who received the classic triple eradication therapy; 3 patients without DM who underwent quadrotherapy with bismuth preparations; 4 patients with type 2 DM who underwent quadrotherapy with bismuth preparations. Eradication therapy was carried out for 14 days. Evaluation of the effectiveness of eradication using a breath test was carried out 4 weeks after completion of the course of treatment. Eradication success was assessed separately for ITT and PP analyzes. The effectiveness of classical triple eradication therapy in patients with concomitant type 2 DM is 64.4% in the ITT group and 69.05% in the PP: quadrotherapy 73.34 and 80.49%, respectively. The effectiveness of first line eradication therapy is higher in patients without DM compared with groups of patients with concomitant type 2 DM: ITT 83.33%, PP 88.23% and ITT 68.89%, PP 74.70%, respectively. The incidence of side effects in patients with type 2 DM: with the use of classical triple therapy 22.23%, quadrotherapy 31.12%. The data of the study of the efficacy and safety of line I eradication therapy make it possible to recommend the four-component therapy based on bismuth for use in clinical practice, especially in patients with DM.

Next-Generation Sequencing-Based Study of Helicobacter pylori Isolates from Myanmar and Their Susceptibility to Antibiotics

Evaluation of Helicobacter pylori resistance to antibiotics is crucial for treatment strategy in Myanmar. Moreover, the genetic mechanisms involved remain unknown. We aimed to investigate the prevalence of H. pylori infection, antibiotic resistance, and genetic mechanisms in Myanmar. One hundred fifty patients from two cities, Mawlamyine (n = 99) and Yangon (n = 51), were recruited. The prevalence of H. pylori infection was 43.3% (65/150). The successfully cultured H. pylori isolates (n = 65) were tested for antibiotic susceptibility to metronidazole, levofloxacin, clarithromycin, amoxicillin, and tetracycline by Etest, and the resistance rates were 80%, 33.8%, 7.7%, 4.6%, and 0%, respectively. In the multidrug resistance pattern, the metronidazole–levofloxacin resistance was highest for double-drug resistance (16/19; 84.2%), and all triple-drug resistance (3/3) was clarithromycin–metronidazole–levofloxacin resistance. Twenty-three strains were subjected to next-generation sequencing to study their genetic mechanisms. Interestingly, none of the strains resistant to clarithromycin had well-known mutations in 23S rRNA (e.g., A2142G, A2142C, and A2143G). New type mutation genotypes such as pbp1-A (e.g., V45I, S/R414R), 23S rRNA (e.g., T248C), gyrA (e.g., D210N, K230Q), gyrB (e.g., A584V, N679H), rdxA (e.g., V175I, S91P), and frxA (e.g., L33M) were also detected. In conclusion, the prevalence of H. pylori infection and its antibiotic resistance to metronidazole was high in Myanmar. The H. pylori eradication regimen with classical triple therapy, including amoxicillin and clarithromycin, can be used as the first-line therapy in Myanmar. In addition, next-generation sequencing is a powerful high-throughput method for identifying mutations within antibiotic resistance genes and monitoring the spread of H. pylori antibiotic-resistant strains.

Evidence-Based Guidelines for the Treatment of Helicobacter pylori Infection in Korea: 2020 Revised Edition

Helicobacter pylori (H. pylori) infection is one of the most common infectious diseases worldwide. Although its incidence is gradually decreasing, about half of the world's population still get infected. H. pylori infection is responsible for substantial gastrointestinal morbidity worldwide. It is the most common cause of gastric and duodenal ulcers as well as gastric cancer. Since the revision of the H. pylori Clinical Practice Guidelines in 2013, the eradication rate of H. pylori has gradually decreased with the use of classical triple therapy, wherein amoxicillin, clarithromycin, and proton pump inhibitors are administered, for 7 days. According to a nationwide randomized controlled study conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research released in 2018, the intention-to-treat eradication rate was only 63.9%, which was due to increased antimicrobial resistance induced by the use of antibiotics, especially clarithromycin. The update of clinical practice guideline for treatment of H. pylori was developed based on evidence-based medicine by conducting a meta-analysis. The draft recommendations were finalized after expert consensus on three recommendations regarding the indication for treatment and eight recommendations on the treatment itself. These guidelines are designed to provide patients, nurses, medical school students, policymakers, and clinicians with clinical evidence to guide primary care and treatment of H. pylori infection. These may differ from current medical insurance standards and will be revised further, if necessary, based on research-based evidence.

Резистентность Helicobacter pylori к кларитромицину в Российской Федерации

Purpose – the systematization of data on the resistance of Helicobacter pylori to clarithromycin in the Russian Federation. Material and methods. Necessary investigations were searched in the electronic databases MEDLINE/PubMed, EMBASE, Cochrane, and the Russian Science Citation Index (RSCI), published between January and September, 2020. The final analysis included original publications from periodically reviewed foreign and Russian publications, as well as dissertations that used validated H. pylori resistance assessment tests with detailed descriptive statistics that allow the resulting data to be included in the meta-analysis. Results. The final analysis included 16 studies (1227 isolates). The generalized indicator of H. pylori resistance to clarithromycin in the Russian Federation was 11.85% (95% confidence interval (CI) 7.315–17.302; I2 = 86.19%). When analyzing papers published over the past ten years, H. pylori resistance to clarithromycin was 10.39% (95% CI 7.103–14.219; I2 = 61.29%). In Moscow and the Moscow Region, the generalized indicator of H. pylori resistance to clarithromycin was 10.87% (95% CI 7,280–15,439; I2 = 50.57%), in St. Petersburg – 22.26% (95% CI 9,525–38,470; I2 = 84.75%), Smolensk – 5.74% (95% CI 3,511–8,789; I2 = 0.00%), Kazan – 10.0% (95% CI 5,023–17,355; I2 = 45.22%). Conclusion. The results show that the resistance of H. pylori to clarithromycin in Russia does not exceed the 15% threshold regulated by the Maastricht-V Consensus, which allows us to consider a triple regimen of anti-Helicobacter therapy with clarithromycin as a first-line therapy. At the same time, to achieve the maximum effect when using classical triple therapy and to level the risk of further progression of clarithromycin resistance of H. pylori in Russia, it is advisable to use methods of its optimization.

Evidence-based Guidelines for the Treatment of Helicobacter pylori Infection in Korea: 2020 Revised Edition

Helicobacter pylori (H. pylori) infection is one of the most common infectious diseases worldwide. Although its incidence is gradually decreasing, about half of the world's population still get infected. H. pylori infection is responsible for substantial gastrointestinal morbidity worldwide. It is the most common cause of gastric and duodenal ulcers as well as gastric cancer. Since the revision of the H. pylori Clinical Practice Guidelines in 2013, the eradication rate of H. pylori has gradually decreased with the use of classical triple therapy, wherein amoxicillin, clarithromycin, and proton pump inhibitors are administered, for 7 days. According to a nationwide randomized controlled study conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research released in 2018, the intention-to-treat eradication rate was only 63.9%, which was due to increased antimicrobial resistance induced by the use of antibiotics, especially clarithromycin. The update of clinical practice guideline for treatment of H. pylori was developed based on evidence-based medicine by conducting a meta-analysis. The draft recommendations were finalized after expert consensus on three recommendations regarding the indication for treatment and eight recommendations on the treatment itself. These guidelines are designed to provide patients, nurses, medical school students, policymakers, and clinicians with clinical evidence to guide primary care and treatment of H. pylori infection. These may differ from current medical insurance standards and will be revised further, if necessary, based on research-based evidence.

Comparison of Classical Triple Therapy and Classical Triple + Bismuth Therapy for Eradication of Helicobacter Pylori

Amaç: Kliniğimize başvuran peptik ülserli, Helikobakter Pilori (HP) pozitif hastalarda klasik üçlü tedavi verilen hastalarla klasik üçlü tedaviye bizmut eklenen hastalar arasındaki HP eradikasyon oranının karşılaştırılması amaçlanmaktadır.Materyal ve Metod: Ocak 2012- Ocak 2013 tarihleri arası prospektif olarak, endoskopilerinde gastrik ve/veya duodenal ülser (peptik ülser) saptanan, histopatoloji, üre nefes testi ya da dışkıda HP antijeni sonuçlarından herhangi birinde pozitiflik saptanan 60 hasta ardışık olarak çalışmaya alındı. Grup 1 hastalara (n=30) klasik üçlü tedavi, grup 2 hastalara (n=30) klasik üçlü tedavi+bizmut tedavileri uygulandı. 3 ay sonra her iki grubun tedavi etkinliği istatistiksel olarak karşılaştırıldı.Bulgular: Dışkıda HP antijeni saptanması testi ile grup 1’ de %83,3, grup 2’ de %73,3 eradikasyon olduğu belirlendi. Dışkıda HP antijeni saptanması ile yapılan değerlendirmede her iki grup arasında tedavi etkinliği açısından herhangi bir fark saptanmadı (p=0,532). Üre nefes testi ile grup 1’ de %56,7, grup 2’ de %53,3 eradikasyon olduğu belirlendi. Üre nefes testi ile yapılan değerlendirmede her iki grup arasında tedavi etkinliği açısından herhangi bir fark saptanmadı (p=0,795). Tüm tedavi alanlarda dışkıda HP antijeni testi ile eradike olma oranı üre nefes testine göre daha fazla görüldü, istatiksel olarak anlamlı idi (p=0,011). Sonuç: Klasik üçlü tedavi ile klasik üçlü tedavi+ bizmut tedavisi arasında eradikasyon açısından herhangi bir farklılık saptanmamıştır. Bu yüzden klaritromisin direnci göz önünde bulundurularak seçilecek tedavi ona göre belirlenmelidir. Ayrıca tedavi sonrası etkinliği değerlendirmede dışkıda HP antijeni testi ile üre nefes testi arasında anlamlı fark bulunup dışkıda HP antijeni ile eradikasyon oranı daha yüksek görünmektedir.

The efficacy and safety of quadruple therapy without bismuth (concomitant therapy) in the treatment of patients with Helicobacter pylori - associated gastric and duodenal peptic ulcer disease

Evaluation of the efficacy and safety of quadrupletherapy without bismuth (concomitant therapy) in patients with Helicobacter pylori - associated gastric ulcer and duodenal ulcer in the framework of a comparative research in the population of patients in Russia. A prospective randomized trial was conducted, which included 210 patients with H. pylori - associated gastric/duodenal ulcer without complications. During the process of randomization, the patients were divided into three equal groups (n=70) depending on the prescribed 10-day scheme of eradication therapy (ET): the first group received the classic triple scheme (Omeprazole 20 mg 2 times a day, Amoxicillin 1000 mg 2 times a day and Clarithromycin 500 mg 2 times a day); the second group received quadruple therapy with bismuth drugs (Omeprazole 20 mg 2 times a day, Tetracycline 500 mg 4 times a day, Metronidazole 500 mg 3 times a day, Bismuth subcitrate potassium 120 mg 4 times a day); the third group received quadruple therapy without bismuth - concomitant therapy (Omeprazole 20 mg 2 times a day, Amoxicillin 1000 mg 2 times a day, Clarithromycin 500 mg 2 times a day and Metronidazole 500 mg 2 times a day). Diagnostics of H. pylori infection during screening and control of eradication was carried out via the fast urease biopsy sample test and urea breath test system. Control of the effectiveness of ET of the microorganism was carried out not earlier than 4 weeks after the end of the treatment. During the course of therapy, the frequency of development of side effects was assessed using a special questionnaire. The effectiveness of triple therapy was 72.8% (ITT; 95% CI of 62.17-83.54) and 78,4% (PP; 95% CI 68.19-88.72); quadruple therapy with the preparation of bismuth - 80.0% (ITT; 95% CI 70.39-89.6) and 84,8% (PP; 95% CI, 75.96-93.73); quadruple therapy without bismuth - concomitant therapy - 84.2% (ITT; 95% CI 75.54-93.02) and 92.1% (PP; 95% CI 85.43-98.94). Quadruple therapy without bismuth was reliably more effective than the classical triple therapy in the PP selection (p=0.044883). Statistical analysis showed a tendency to poorer effectiveness of ET in patients who had previously used antibiotic therapy (OR 0.4317; 95% CI 0.1776-1.049), and in individuals with a rapid metabolism genotype - CYP2C19*1/*1 (OR 0.12; 95% CI 0.005848-2.4624). The frequency of development of side effects during the use of triple therapy was 18.5% (95% CI of 9.23-27.91), when using quadruple therapy with bismuth - 20.0% (95% CI 10.39-29.6), and with the use of quadruple therapy without bismuth - concomitant therapy - 24.2% (95% CI 13.98-34.58). This prospective randomized study demonstrated the high efficiency of quadruple therapy without bismuth (concomitant therapy) in the framework of eradication of H. pylori infection in Russia.

Refractory Helicobacter pylori gastritis: The hidden predictors of resistance.

Failure of Helicobacter pylori eradication is documented in 20% of patients. Some patients show a negative faecal antigen test (FAT) with persistent symptoms after therapy. The aim of this study was to detect occult H. pylori infection in patients with persistent symptoms despite FAT negativity following therapy. A total of 200 symptomatic patients presenting with dyspepsia and positive FAT were treated with H. pylori triple therapy for 2 weeks. Refractory patients received levofloxacin-based salvage therapy. Upper gastrointestinal endoscopy was performed for patients with persistent symptoms despite negative FAT after salvage therapy. Gastric biopsies were exposed to rapid urease test and RFLP-PCR for clarithromycin resistance in domain V of 23S rRNA (2142/2143 point mutations) as well as culture and antimicrobial susceptibility testing (AST). A total of 136 patients responded to classic triple therapy with negative FAT, and 15 patients showed persistent symptoms with positive FAT and received salvage therapy. The remaining 49 patients showed persistent symptoms despite negative FAT, therefore gastric biopsies with rapid urease test were performed. Clarithromycin resistance was confirmed in 12/49 patients (24.5%). Cultures were most commonly susceptible to norfloxacin (n=18), moxifloxacin (n=13), doxycycline (n=11) and amikacin (n=8). Non-responders with negative FAT had moderate or severe fatty liver disease (26.5% and 32.7%, respectively), 40.9% had hepatitis C virus (HCV) infection, and they had significantly higher HOMA-IR and HbA1c. Diabetes mellitus, HCV and non-alcoholic fatty liver disease predispose to refractory H. pylori requiring culture and AST.

Helicobacter pylori: qué debemos saber en el año 2018. Revisión de la evidencia y nuevas recomendaciones de tratamiento

Helicobacter pylori (HP) is the most widely chronic human infection around the world, and
 the main risk factor for the development of gastric cancer. Our country has high rates of
 this neoplasia and a high prevalence of HP infection. Even both have fallen in the last year,
 is a major concern to diagnose the population infected with HP in early stages, before the
 development of premalignant lesions and properly eradicate this infection. In this review, we
 discussed the different methods for the diagnosis of HP and factors that change positivity
 as the use of proton pump inhibitors. Also, we discussed the factors to be considered in the
 choice of the treatment, like local resistance to antibiotics, specially clarithromycin. In the last
 years has been documented in Chile a significant increase in resistance to clarithromycin, from
 20 to 46%, which predicts inadequate effectiveness for the classic triple therapy. As the result
 of the previous analysis we discussed new possible therapies, including bismuth quadruple
 therapy and concomitant therapy.

Antithrombotic Regimens in Patients With Percutaneous Coronary Intervention Whom an Anticoagulant Is Indicated: A Systematic Review and Network Meta-Analysis.

Background: Patients undergoing percutaneous coronary intervention (PCI) who require anticoagulant therapy are at increased risk of bleeding. The optimal regimen for these patients is uncertain. This study aimed to compare safety and efficacy of antithrombotic regimens used in patients undergoing PCI with concomitant anticoagulant therapy.Methods: A systematic review and network meta-analysis was performed among studies comparing antithrombotic regimens for anticoagulated patients undergoing PCI. The primary outcome of interest was major bleeding. The secondary outcomes were coronary events. The reference intervention was classic triple therapy (aspirin plus clopidogrel plus VKA). Cluster rank incorporating risk (major bleeding) and benefit (all-cause death) was performed to identify the most appropriate regimen(s).Results: There were 3 RCTs (6 interventions) and 29 non-RCTs (8 interventions) that met the inclusion criteria with 22,179 patients. Network meta-analysis of RCTs indicated that dual therapy (DT), either with vitamin K antagonist (VKA) or direct anticoagulant (DOAC) plus an antiplatelet, significantly reduced the risk of major bleeding compared to triple therapy (TT) [pooled RR of 0.51 (0.30–0.87) and 0.68 (0.49–0.94), respectively]. In addition, VKA-DT significantly reduced the risk of all-cause death compared to TT [pooled RR of 0.40 (0.17–0.93)]. Results from network meta-analysis of non-RCT paralleled that of RCTs. No significant differences of coronary events were found.Conclusions: In conclusion, for anticoagulated patients undergoing PCI, dual therapy, either with warfarin or DOAC plus an antiplatelet, should be considered due to its optimal balance on efficacy and safety.

Eradication rate of Helicobacter pylori by classic triple therapy in Lebanon: Is it still effective?

Eradication rate of Helicobacter pylori by classic triple therapy in Lebanon: Is it still effective?

Levofloxacin based vs clarithromycin based sequential therapy in helicobacter pylori eradication; a randomized clinical trial.

This study was aimed to evaluating the efficacy of levofloxacin based sequential therapy vs clarithromycin based sequential therapy in h.pylori (HP) eradication. Several therapeutic regimen were investigated to treat HP infection. Sequential therapy is an alternative to classic triple therapy. In this randomized clinical trial, 200 HP infected patients randomly divided into two therapeutic groups .1-Levofloxacin based sequential regimen (group A); omeprazole and amoxicillin for 7days followed by omeprazole, amoxicillin and levofloxacin for 7days. 2-clarithromycin based sequential regimen (group B): omeprazole and amoxicillin for 7days followed by omeprazole, amoxicillin and clarithromycin for 7days. HP eradication was evaluated with urea breath test with carbon 13 (UBT) 6 weeks after the end of treatment. Per protocol eradication rates of group A and B were 87.6% and 76% respectively. By intention to treat analysis, eradication rate of group A and B groups were 85.1% and 73% respectively. Levofloxacin based sequential regimen was more effective than clarithromycin based sequential regimen (Pv=0.028). Adverse events were seen in 19.6% and 15.6% in group A and B respectively. Drug compliance was 97% in group A and 96% in group B. There was no significant difference between two groups in term of adverse events (p=0.470) and compliance (p=0.651). Levofluxacin based sequential therapy was more effective than Clarithromycin based sequential therapy in HP eradication. The suggested Levofluxacin based sequential therapy could be an alternative therapy in area with high clarithromycin resistance. Further studies are needed to confirm these findings.

Levofloxacin-based sequential therapy versus classic triple therapy in Helicobacter pylori eradication: A randomized clinical trial

Introduction: During the past two decades, eradication rates with triple therapy for Helicobacter (H.) pylori eradication have decreased. The decline of effectiveness of the triple therapy have led to investigations to achieve more effective and safe therapeutic strategies. Sequential, concomitant and hybrid therapeutic regimens are new therapies that have been introduced over the past two decades. The purpose of this study was to compare levofloxacin-based sequential therapy versus classic triple therapy in H. pylori eradication in a randomized clinical trial.
 Methods: All eligible cases were divided into two groups using a randomized block method. The first group (classic group) was treated with triple therapy; patients received omeprazole, amoxicillin and clarithromycin for 14 days. The second group received the levofloxacin-based sequential (lev-seq) regimen; the patients were treated with omeprazole and amoxicillin for the first 7 days and then with omeprazole, levofloxacin and metronidazole for the latter 7 days. In this clinical trial, 200 patients with H. pylori infection were enrolled. Ultimately, 192 patients completed the study. Of these, 95 patients (46 males and 49 females) were treated with triple therapy (classic group) and 97 patients (46 males and 51 females) were treated with the lev-seq regimen. The average age in the classic group and lev-seq groups were 41.4±12.4 years and 40.2±11.8 years, respectively.
 Results: The levofloxacin based sequential regimen was more effective than triple therapy regimen. It is recommended that the lev-seq regimen be used as the first-line therapy, especially in areas with high levels of resistance to clarithromycin (over 20%).
 Conclusion: Further studies with large numbers of samples are required to be conducted in different parts of the country for further evaluation of efficacy of this regimen.
 Peer Review Details
 
 
 
 
 
 Peer review method: Single-Blind (Peer-reviewers: 02) Peer-review policy 
 Plagiarism software screening?: Yes
 Date of Original Submission: 05 November 2017
 Date accepted: 25 November 2017
 Peer reviewers approved by: Dr. Lili Hami 
 Editor who approved publication: Dr. Phuc Van Pham
 
 
 
 
 

Therapeutic success with bismuth-containing sequential and quadruple regimens in Helicobacter pylori eradication

Background and study aimsThe success rate of Helicobacter pylori (H. pylori) eradication with the classical triple therapy is gradually declining. In this study, we aimed to compare and assess the efficacies of six different eradication regimens including sequential protocols. Patients and methodsEndoscopically confirmed nonulcer dyspepsia patients were enrolled. H. pylori presence was determined either histologically or by a rapid urease test. Treatment-naive patients were randomly assigned to an either one of three 10-day (OAC, OTMB, and OACB) or one of three sequential protocols (OA+OCM, OA+OCMB, and OA+OMDB) (O=omeprazole, A=amoxicillin, C=clarithromycin, T=tetracycline, M=metronidazole, B=bismuth, D=doxycycline). The eradication was assessed 6–8weeks after the completion of the treatment by a 14C-urea breath test. ResultsIn total, 301 patients were included. Fifty-two percent of the participants (n=157) were female, and the mean age was 44.9years (range=18–70). The intention to treat (ITT) and per protocol (PP) eradication rate for each regimen is as follows: OAC (ITT=61.2%, PP=75%), OTMB (83.3%, 87%), OACB (76.5%, 79.6%), OA+OCM (72.3%, 73.9%), OA+OCMB (82.7%, 89.6%), and OA+OMDB (59.3%, 65.3%). Smoking significantly affected the eradication rate (P=0.04). ConclusionIn this study, OTMB and OA+OCMB were significantly superior to the triple therapy and succeeded to reach the eradication rate proposed by the Maastricht consensus (over 80%). These two bismuth-containing regimens could be considered for first-line therapy in the regions with high clarithromycin resistance.

NEW PROSPECTS OF ANTITHROMBOTIC THERAPY IN PATIENTS WITH ATRIAL FIBRILLATIO AND CORONARY ARTERY STENTS: DABIGATRAN POTENTIAL

After percutaneous coronary intervention, patients receive double antiplatelet therapy for several months, which includes acetylsalicylic acid and a P2Y12 receptor inhibitor. In most cases, managing the patients with the atrial fibrillation requires adding an anticoagulant drug to the antiplatelet therapy — triple antithrombotic therapy. The rejection of triple therapy in favour of the administration of an anticoagulant and only one antiaggregant is a prospective line of reducing the risk of bleeding in these patients. The number of studies evaluating the effectiveness and safety of such therapy remains limited, and the guidelines for anticoagulant therapy are largely based on the studies of only "stable" patients with atrial fibrillation and on the results of registers, i.e. data of “real-life” clinical practice. The RE-DUAL PCI study showed that the administration of dabigatran in combination with the P2Y12 receptor inhibitor in patients with atrial fibrillation after percutaneous coronary intervention is much safer and no less effective than the classical triple therapy. A special feature of the study was the evaluation of the effectiveness and safety of two doses of dabigatran, each of which was approved for stroke prevention. This provides clinicians with additional options for treating patients with atrial fibrillation after percutaneous coronary intervention.

Addition of Rifaximin and N-Acetyl Cysteine to the Standard Helicobacter pylori Treatment Regimens: Is it Possible to Improve Outcomes?

Aim: We demonstrated a decade ago that standard triple therapy was unsuccessful in Helicobacter pylori (H.pylori) eradication in our region. Unfortunately, the eradication studies we have done with different therapy charts so far have proved insufficient as well. Thus, we aimed to compare combinations containing rifaximin with or without N-acetyl cysteine (NAC) with standard triple and bismuth based quadruple therapy in a prospective randomized study with the purpose of increasing eradication success. Materials-Methods: Patients who were infected with H.pylori were included in the study. The patients were separated into 5 groups according to eradication treatments: Group A: RAC (rabeprazole 2 × 20 mg, amoxicillin 2 × 1000 mg, clarithromycin 2 × 500 mg), Group B: RAM (rabeprazole 2 × 20 mg, amoxicillin 2 × 1000 mg, metronidazole 3 × 500 mg), Group C: RBTM: (rabeprazole 2 × 20 mg, bismuth subcitrate 4 × 300 mg, tetracyclin 4 × 500 mg, metronidazole 3 × 500 mg), Group D: RARX (rabeprazole 2 × 20 mg, amoxicillin 2 × 1000 mg, rifaximin 2 × 400 mg), Group E: RARXNAS (rabeprazole 2 × 20 mg, amoxicillin 2 × 1000 mg, rifaximin 2 × 400 mg, N-acetyl cysteine 2 × 600 mg). The treatments were applied for 14 days. At least 4 weeks after the completion of treatment, eradication was confirmed by the urea breath test. Results: A total of 339 patients were included in the study. 303 patients completed the study (89%). The eradication rates were determined to be 54% and 59% for Group A, 48% and 55% for Group B, 52% and 59% for Group C, 39% and 43% for Group D, 37% and 38% for Group E, as intention-to-treat (ITT) and per-protocol (PP) respectively. There were no significant side effects. Conclusion: It was observed that eradication results of classical triple and quadruple therapy schedules were once again quite insufficient. Therapy regimens containing rifaximin, however, had worse results, even when NAC was added.

A Lyophilized Form of Saccharomyces Boulardii Enhances the Helicobacter pylori Eradication Rates of Omeprazole-Triple Therapy in Patients With Peptic Ulcer Disease or Functional Dyspepsia

Background: Saccharomyces boulardii prevents antibiotic-induced diarrhea and exerts anti- H.pylori effects in vitro and in vivo . Aim: To assess whether S. boulardii enhances the efficacy of classic triple therapy in eradicating H. pylori . Methods: Seventy patients with peptic ulcer or functional dyspepsia according to Rome III criteria and H. pylori infection were treated with omeprazole 20 mg bid, clarithromycin 500 mg bid and amoxicillin 1 g bid for 14 days. A total of 36 out of 70 (51%) patients were randomized to S. boulardii [Ultralevure®, two capsules tid for 14 days (group A) and 34 (49%) on no intervention (group B). H. pylori eradication was assessed by a 13 C-Urea Breath Test. Results: At baseline there were no significant differences between the two groups in any patient or disease characteristics. H. pylori was eradicated in 30/36 (83.4%) patients in group A vs 20/34 (58.8%) in group B ( P =0.034, 95% CI 4.4% to 43.6%). Seven patients in group B (20.6%) and 1 patient in group A stopped treatment because of diarrhea (95% CI 3.3% to 32.7%, P =0.026). Multi-factorial analysis did not reveal any patient or disease related parameter linked to treatment outcome except for the use of the probiotic. Conclusion: S. boulardii enhanced the effect of classic triple therapy mainly by preventing antibiotic- and/or proton pump inhibitor-induced diarrhea.

PRIMARY ANTIMICROBIAL RESISTANCE OF HELICOBACTER PYLORI IN BELGIUM

The increasing antimicrobial resistance of Helicobacter pylori jeopardizes the efficiency of the classical eradication triple therapy. In this article we assessed the primary resistance rates of Helicobacter pylori to the commonly used antibiotics for eradication in the area of Brussels and determined prospectively, through a questionnaire, the possible risk factors for resistance. Gastric biopsies were taken for histology and culture in all adult patients in whom Helicobacter pylori was searched from February 2009 to April 2010 at the UZBrussel hospital. Clinical and demographic data were collected through a questionnaire. Histology was positive in 222 out of 507 patients tested (43.7%). Culture was successful in 189 patients with a positive histology (85.1%), 4 patients had a positive culture with a negative histology. Resistance to clarithromycin, metronidazole, ciprofloxacin, and amoxicillin was tested. Primary resistance rates were 13.3% for clarithromycin, 26.1% for metronidazole, 23.9% for ciprofloxacin, 0.8% for amoxicillin. Dual resistance to claritromycin and metronidazole was seen in 3.9%, triple resistance (claritromycin, metronidazole and ciprofloxacin) in 1.7% and resistance to the 4 antibiotics in 0.6% of patients. We conclude that there is a decreasing resistance for clarithromycin, metronidazole resistance is stable and rapidly increasing ciprofloxacin resistance. Resistance to any of the tested antibiotics was not associated with origin, age, gender, number of siblings, level of education or disease status (p > 0.05).