High Clarithromycin Resistance Research Articles

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.

Fourteen-day vonoprazan-based bismuth quadruple therapy for H. pylori eradication in an area with high clarithromycin and levofloxacin resistance: a prospective randomized study (VQ-HP trial)

Potassium-competitive acid blockers (P-CABs) provide potent acid inhibition, yet studies on P-CAB-based quadruple therapy for H. pylori eradication are limited. We theorized that integrating bismuth subsalicylate into a quadruple therapy regimen could enhance eradication rates. However, data on the efficacy of vonoprazan bismuth quadruple therapy are notably scarce. Therefore, the aim of this study was to evaluate the efficacy of vonoprazan-based bismuth quadruple therapy in areas with high clarithromycin and levofloxacin resistance. This was a prospective, single-center, randomized trial conducted to compare the efficacy of 7-day and 14-day vonoprazan-based bismuth quadruple therapy for H. pylori eradication between June 1, 2021, and March 31, 2022. Qualified patients were randomly assigned to the 7-day or 14-day regimen (1:1 ratio by computer-generated randomized list as follows: 51 patients for the 7-day regimen and 50 patients for the 14-day regimen). The regimens consisted of vonoprazan (20 mg) twice daily, bismuth subsalicylate (1024 mg) twice daily, metronidazole (400 mg) three times daily, and tetracycline (500 mg) four times daily. CYP3A4/5 genotyping and antibiotic susceptibility tests were also performed. Successful eradication was defined as 13negative C-UBTs 4 weeks after treatment. The primary endpoint was to compare the efficacy of 7-day and 14-day regimens as first-line treatments, which were assessed by intention-to-treat (ITT) and per-protocol (PP) analyses. The secondary endpoints included adverse effects. A total of 337 dyspeptic patients who underwent gastroscopy were included; 105 patients (31.1%) were diagnosed with H. pylori infection, and 101 patients were randomly assigned to each regimen. No dropouts were detected. The antibiotic resistance rate was 33.3% for clarithromycin, 29.4% for metronidazole, and 27.7% for levofloxacin. The CYP3A4 genotype was associated with 100% rapid metabolism. The H. pylori eradication rates for the 7-day and 14-day regimens were 84.4%, 95% CI 74.3–94.2 and 94%, 95% CI 87.4–100, respectively (RR difference 0.25, 95% CI 0.03–0.53, p value = 0.11). Interestingly, the 14-day regimen led to 100% eradication in the clarithromycin-resistant group. Among the patients in the 7-day regimen group, only two exhibited resistance to clarithromycin; unfortunately, neither of them achieved a cure from H. pylori infection. The incidence of adverse events was similar in both treatment groups, occurring in 29.4% (15/51) and 28% (14/50) of patients in the 7-day and 14-day regimens, respectively. No serious adverse reactions were reported. In conclusion, 14 days of vonoprazan-based bismuth quadruple therapy is highly effective for H. pylori eradication in areas with high levels of dual clarithromycin and levofloxacin resistance.

Independent risk factors predicting eradication failure of standard bismuth quadruple therapy for the first‐line treatment of Helicobacter pylori infection in Taiwan

AbstractBismuth quadruple therapy is recommended as the choice treatment for Helicobacter pylori (H. pylori) infection in areas of either low or high clarithromycin resistance in the Maastricht VI/Florence Consensus Report. However, the optimal treatment duration and drug dosages of bismuth quadruple therapy remain unclear. The study aimed to search the independent risk factors predicting eradication failure of standard bismuth quadruple therapy in the first‐line treatment of H. pylori infection. From July 2014 to June 2022, 274 H. pylori‐infected patients who received 10‐day or 14‐day bismuth quadruple therapy containing a proton pump inhibitor, bismuth, tetracycline and metronidazole were included for the study. Post‐treatment H. pylori status was assessed at least 4 weeks after completion of treatment. The relationships between eradication rate and 13 clinical parameters were analyzed by univariate and multivariate analyses. The eradication rates of standard bismuth quadruple therapy were 93.8% and 94.2% by intention‐to‐treat and per‐protocol analyses, respectively. Univariate analysis revealed that patients harboring metronidazole‐resistant strains had a lower eradication rate than those harboring metronidazole‐susceptible strains (88.7% [55/62] vs. 96.7% [148/153]). The other factors including smoking, treatment duration and drug adherence were not significantly associated with cure rate. Multivariate analysis revealed that metronidazole resistance of H. pylori was the only independent risk factors related to eradication failure of standard bismuth quadruple therapy with an odds ratio of 3.8 (95% CI: 1.2–12.4). In conclusion, metronidazole resistance is an independent risk factor predicting eradication failure of standard bismuth quadruple therapy in the first‐line treatment of H. pylori infection. There is no difference in eradication efficacy between 10‐day and 14‐day bismuth quadruple therapies in Taiwan.

Concomitant and Bismuth Quadruple Therapy for Helicobacter pylori Eradication in Southern Italy: Preliminary Data from a Randomized Clinical Trial.

Concomitant therapy (CT) and bismuth quadruple therapy (BQT) are recommended in geographical areas with high clarithromycin resistance for Helicobacter pylori (H. pylori) eradication. We compared CT and BQT as the first lines of treatment in a randomized controlled trial. Consecutive patients with H. pylori diagnosed by concordance of both a urea breath test and histology were recruited. For BQT, patients received 3 PyleraTM capsules q.i.d.; for CT, 1000 mg of amoxicillin b.i.d, 500 mg of clarithromycin b.i.d and 500 mg of metronidazole b.i.d. As a proton pump inhibitor, 40 mg of pantoprazole b.i.d was administered. Both regimens lasted 10 days. In total, 46 patients received CT and 38 BQT. Both groups were comparable for age (p = 0.27) and sex (p = 0.36). We did not record any drop outs; therefore, the intention to treat and per protocol rates coincided. The most common symptoms were heartburn and post-prandial fullness, which were equally present in both groups. The success rate was 95.6% for CT and 100% for BQT (p = 0.56). Side effects were recorded in 23.9% and 31.6% of patients in the CT and BQT arms, respectively (p = 0.47). The most common ones were abdominal pain (8) and diarrhea (6). In conclusion, CT and BQT are equally effective in our area with high clarithromycin resistance, southern Italy, and showed comparable safety.

Equivalence Trial of the Non-Bismuth 10-Day Concomitant and 14-Day Hybrid Therapies for Helicobacter pylori Eradication in High Clarithromycin Resistance Areas.

Background and aim: We conducted an equivalence trial of quadruple non-bismuth "concomitant" and "hybrid" regimens for H. pylori eradication in a high clarithromycin resistance area. Methods: There were 321 treatment-naïve H. pylori-positive individuals in this multicenter clinical trial randomized to either the hybrid (esomeprazole 40 mg/bid, amoxicillin 1 g/bid for 7 days, then 7 days esomeprazole 40 mg/bid, amoxicillin 1 g/bid, clarithromycin 500 mg/bid, and metronidazole 500 mg/bid) or the concomitant regimen (all medications given concurrently bid for 10 days). Eradication was tested using histology and/or a 13C-urea breath test. Results: The concomitant regimen had 161 patients (90F/71M, mean 54.5 years, 26.7% smokers, 30.4% ulcer) and the hybrid regimen had 160 (80F/80M, mean 52.8 years, 35.6% smokers, 31.2% ulcer). The regimens were equivalent, by intention to treat 85% and 81.8%, (p = 0.5), and per protocol analysis 91.8% and 87.8%, (p = 0.3), respectively. The eradication rate by resistance, between concomitant and hybrid regimens, was in susceptible strains (97% and 97%, p = 0.6), clarithromycin single-resistant strains (86% and 90%, p = 0.9), metronidazole single-resistant strains (96% and 81%, p = 0.1), and dual-resistant strains (70% and 53%, p = 0.5). The side effects were comparable, except for diarrhea being more frequent in the concomitant regimen. Conclusions: A 14-day hybrid regimen is equivalent to a 10-day concomitant regimen currently used in high clarithromycin and metronidazole resistance areas. Both regimens are well tolerated and safe.

Systematic Review and Meta-Analysis: Bismuth Enhances the Efficacy for Eradication of Helicobacter pylori.

In the eradication of Helicobacter pylori, the efficacy of bismuth remains inconclusive. We aimed to compare the efficacy of bismuth on various H. pylori eradication regimens. Randomized controlled trials were collected to compare the efficacy of bismuth to nonbismuth regimens in H. pylori eradication. We pooled information to study eradication, adverse events, and drug compliance. In addition, subgroup analyses for eradication efficacy were performed according to high or low clarithromycin-resistance area, bismuth drug form, and amount of bismuth element. Records for a total of 2506 patients in 15 trials from 13 randomized controlled studies were included. The eradication of H. pylori was superior when bismuth compared to nonbismuth regimen (odds ratio [OR] = 1.63, 95% confidence interval [CI], 1.33-2.00 in intention-to-treat [ITT]; OR = 2.05, 95% CI, 1.58-2.68 in per-protocol [PP] analyses), without significant difference in drug compliance or adverse events. Bismuth regimens in the high clarithromycin resistance area tend to enhance the eradication rate (OR = 1.66, 95% CI, 1.34-2.05 in ITT; OR = 2.22, 95% CI, 1.67-2.95 in PP analyses). Bismuth potassium citrate and bismuth subcitrate were more effective drug forms in regard to eradication rate. Bismuth at a dosage of < 500 mg/day was significantly higher for the eradication rate. Bismuth to the H. pylori eradication regimens achieve a higher eradication rate, especially in the high clarithromycin resistance area. It could be an eradication option achieving sufficient resistance rates without increasing antibiotic resistance, side effects, or poor compliance.

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

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. To investigate secondary resistance rates, explore risk factors for antibiotic resistance, and assess the efficacy of susceptibility-guided therapy. 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. 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. 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.

Molecular Identification of Strains within the Mycobacterium abscessus Complex and Determination of Resistance to Macrolides and Aminoglycosides.

One of the most relevant and pathogenic groups among the rapidly growing mycobacteria (RGM) is Mycobacterium abscessus complex (MABC) that includes three subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense. The aim of this study was the analysis of prevalence of MABC among other non-tuberculous mycobacteria isolated from patients in the Malopolska Region of Poland, between 2018 and 2021, as well as determination of their subspecies and molecular mechanisms of resistance to macrolides and aminoglycosides. The incidence of MABC was 5,4% (12/223). Eight strains were classified as M. abscessus subsp. abscessus, three as M. abscessus subsp. massiliense and one M. abscessus subsp. bolletii. Molecular analysis showed resistance to macrolides for eight strains of M. abscessus subsp. abscessus associated with erm(41)T28 gene mutations. One strain of M. abscessus subsp. abscessus showed resistance to macrolides (two mutations simultaneously: in erm(41)T28 and rrl genes) and aminoglycosides (point mutation in rrs gene). One strain of M. abscessus subs. bolletii was resistant to macrolides (erm(41)T28 mutation), whereas presented no mutations for aminoglycosides. M. abscessus subsp. massiliense reveal no mutations. High clarithromycin resistance of M. abscessus, determines the urgent need for susceptibility-based treatment. Molecular determination of resistance mechanisms to aminoglycosides and macrolides enables fast and accurate targeted treatment implementation.

Efficacy and safety of Lacticaseibacillus rhamnosus R0011 and Lactobacillus helveticus R0052 as an adjuvant for Helicobacter pylori eradication: a double-blind, randomized, placebo-controlled study

BackgroundHelicobacter pylori eradication is recommended as a way of providing symptomatic relief for dyspepsia. The limited efficacy of triple therapy is a major problem in many countries, including Thailand. Some probiotics have been shown to improve the H. pylori eradication rate and reduce side effects. This study aimed at evaluating the efficacy of probiotic (Lacidofil® STRONG) as adjuvant to standard triple therapy.MethodsThis randomized, double-blind, placebo-controlled study was conducted between July 2020 and June 2022. Eligible patients with H. pylori gastritis (i.e., n=90 out of the 160 patients screened) were randomized to receive 14-day standard triple therapy either with probiotics or with a placebo (N=45/group). The treatment regimen entailed 30 mg lansoprazole administered twice daily, 1,000 mg amoxicillin administered twice daily, and 1 g clarithromycin modified-release formulation administered once daily. A probiotic capsule containing Lacticaseibacillus rhamnosus R0011 and Lactobacillus helveticus R0052 (Lacidofil® STRONG) or placebo were given twice daily during the eradication therapy and for an additional 4 weeks. Successful H. pylori eradication was defined as a negative 13C-urea breath test at least 4 weeks after complete eradication.ResultsAs per-protocol analysis, eradication rates after the 14-day regimen with probiotic or placebo were 90.9% and 75.0% (p=0.047), respectively. Antibiotic susceptibility testing demonstrated high clarithromycin resistance (24%). For clarithromycin-resistant strains, there was no statistical difference in eradication rates between the probiotic and placebo groups. Furthermore, probiotic supplementation significantly reduced treatment side effects, including bloating (OR 0.27 [95% CI 0.10 to 0.75], p=0.012), diarrhea (OR 0.23 [95% CI 0.28 to 0.65], p=0.006), nausea (OR 0.05 [95% CI 0.01 to 0.36], p=0.003), and bitter taste (OR 0.14 [95% CI 0.03 to 0.69], p=0.015). In addition, the probiotic group had lower gastrointestinal symptom rating scale (GSRS) scores (1.46 ± 0.36 vs. 2.65 ± 0.66, p&amp;lt;0.001) and higher SF-36 health-related quality-of-life scores (63.3 ± 10.2 vs. 57.3 ± 13.4, p=0.020) after treatment than the placebo group.ConclusionThe probiotic adjuvant with 14-day standard triple therapy improved the H. pylori eradication rate. Supplementation with Lacidofil® STRONG during the 2-week eradication treatment and 4-week follow-up phase can help to reduce the gastrointestinal side effects of eradication therapy and increase patients’ general health-related quality of life.

Unusually high clarithromycin resistance in Mycobacterium abscessus subsp. abscessus isolated from human gastric epithelium.

Mycobacterium abscessus subsp. abscessus is a rapidly growing facultative intracellular pathogen that usually infects human lung and skin epithelium. Recently, we and another group have shown that it also has the potential to colonize human gastric epithelium, but its significance with respect to gastric diseases remains unclear. Although Helicobacter pylori still remains the only definite gastric pathogen, recent studies have shown that M. abscessus subsp. abscessus also has the potential to colonize human gastric epithelium. M. abscessus subsp. abscessus is known to exhibit multidrug resistance and clarithromycin has been used as the drug of choice. We aimed to determine the clarithromycin resistance profile of 117 (74 rough and 43 smooth) gastric M. abscessus subsp. abscessus strains and to detect the point mutations in rrl and erm (41) genes conferring the resistance. Our data showed 79.48% (19 smooth and 74 rough) of M. abscessus subsp. abscessus strains were resistant to clarithromycin (MIC90 ≤ 512 μg/mL), while 20.51% (24 smooth) were susceptible (MIC90 ≤ 8 μg/mL). Nucleotide sequence analysis of the rrl gene with reference strains of M. abscessus subsp. abscessus did not show any mutation that is relevant to the clarithromycin resistance. However, analysis of erm (41) gene showed that M. abscessus subsp. abscessus strains, which were susceptible to clarithromycin had C, C, G, and C at their nucleotide positions 28, 159, 238, and 330, respectively, while the resistant strains showed T, T, A, and A at the same positions. Based on antibiogram and sequence analysis data we recommend further studies involving genomic analysis to identify the other genes involved in high clarithromycin resistance in gastric M. abscessus subsp. abscessus along with the mechanisms involved.

Real-world practice of Helicobacter pylori management: A survey among physicians in Southeast Asia.

Multidrug-resistant Helicobacter pylori strains are emerging in Southeast Asia. This study evaluates the region's real-world practice in H. pylori management. Physicians who managed H. pylori eradication in daily practice across 10 Southeast Asian countries were invited to participate in an online questionnaire, which included questions about the local availability of antimicrobial susceptibility tests (ASTs) and their preferred eradication regimens in real-world practice. An empiric regimen was considered inappropriate if it did not follow the local guidelines/consensus, particularly if it contained antibiotics with a high reported resistance rate or was recommended not to be empirically used worldwide. There were 564 valid responses, including 314 (55.7%) from gastroenterologists (GIs) and 250 (44.3%) from non-GI physicians. ASTs were unavailable in 41.7%. In countries with low and intermediate clarithromycin resistance, the most common first-line regimen was PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) (72.7% and 73.2%, respectively). Regarding second-line therapy, the most common regimen was bismuth-based quadruple therapy, PBMT (PPI, bismuth, metronidazole, tetracycline) (50.0% and 59.8%, respectively), if other regimens were used as first-line treatment. Concomitant therapy (PPI, amoxicillin, clarithromycin, metronidazole) (30.5% and 25.9%, respectively) and PAL (PPI, amoxicillin, levofloxacin) (22.7% and 27.7%, respectively) were favored if PBMT had been used as first-line treatment. In countries with high clarithromycin resistance, the most common first-line regimen was PBMT, but the utilization rate was only 57.7%. Alarmingly, PAC was prescribed in 27.8% of patients, ranking as the second most common regimen, and its prescription rate was higher in non-GI physicians than GI physicians (40.1% vs. 16.2%, p < 0.001). Choosing inappropriate regimens containing antibiotics with high resistance rates is not uncommon in Southeast Asia, especially among non-GI physicians. In countries with high clarithromycin resistance, the PBMT regimen is underutilized.

Evaluation of Culture and Sensitivity Guided Antibiotic Selection in Eradication of Helicobacter pylori

Abstract Background Helicobacter pylori exhibits antibiotic resistance with regional differences. Antibiotics resistance is the main cause of eradication failure in H. pylori infection, thus our study aimed to evaluate the efficiency of standard triple therapy vs. Antibiotic -culture with susceptibility-based therapy and success rate of each in helicobacter pylori eradication. Methods This study was conducted on 100 patients with dyspepsia undergoing Upper GI Endoscopy in Gastroenterology department at Ain shams university hospital in the period between june2018 and june2019, the volunteered patients were divided into groups A and B. Group A patients received 2 weeks of pantoprazole 40 mg bid +two Antibiotics according to each patient’s result of culture and sensitivity, while Group B patients received 2 weeks of standard triple therapy PPI 40 mg bid + Amoxicillin 1 g bid + Clarithromycin 500 mg bid Results that patients of group A according to their culture and sensitivity results showed Significant increase in number of isolates sensitive to levofloxacin (26) than those resistant to it (14) with p-value 0.1(HS), Significant number of isolates resistant to clarithromycin (36) than those sensitive to it (14) with p-value o.011 and (HS), also Significant increase in number of isolate resistant to amoxicillin (40) than those sensitive to it (10) with p-value 0.003(HS) and finally significant increase in number of isolate resistant to metronidazole (40) than those sensitive to it (10) with p -value 0.003(HS). H. pylori results 4 weeks post treatment in groups A and B showed that there was a Significant number of positive helicobacter pylori patients 4 weeks post tr eatment in group B (30) than in group A (7) with p- value &amp;lt;0.01 (HS) and Significant number of negative helicobacter pylori patients 4 weeks post treatment in group A(43) than in group B (20) with p- value &amp;lt;0.01 (HS). Conclusion 43 of group (A) patients (86%) showed successful helicobacter pylori eradication after culture guided antibiotic therapy. Only 20 of group (B) patients (60%) showed successful h. pylori eradication after standard triple therapy. The study showed high resistant rates of h. pylori to clarithromycin and amoxicillin and metronidazole and gradually increasing resistance against levofloxacin. Countries like Egypt seem to have a high clarithromycin resistance, and a large-scale clinical trial is needed to choose the first -line therapy for eradication of H. pylori infection.

Current trends in &lt;i&gt;Helicobacter pylori&lt;/i&gt; eradication therapy

According to the Maastricht VI consensus, the triple therapy (PPI + clarithromycin + amoxicillin) and bismuth-based quadruple therapy (PPI + bismuth + tetracycline + metronidazole) are considered and may be proscribed empirically as first-line regimens in the regions with low clarithromycin resistance rates (&lt;15%). In the regions with high clarithromycin resistance rates (&gt; 15%), as well as in the regions with unknown resistance to this antibacterial agent, it is recommended to use classical quadruple therapy with bismuth drugs as the main choice and quadruple therapy without bismuth drugs (“simultaneous” or “concomitant”) as an alternative. The second-line regimens of empiric choice (when antimicrobial susceptibility testing is not available) include fluoroquinolone-based quadruple therapy (PPI + levofloxacin + amoxicillin + bismuth) or fluoroquinolone-based triple therapy (PPI + levofloxacin + amoxicillin) and bismuth-based quadruple therapy. The Maastricht VI consensus regulates the use of rifabutin-based triple therapy (PPI + amoxicillin + rifabutin) as a “rescue” therapy, if the above ET schemes are ineffective and there is no possibility to conduct an antimicrobial susceptibility test. In its latest clinical guidelines, the Russian Gastroenterological Association (RGA) recommends with a view to achieving maximum treatment efficiency during classic triple ET and levelling the risk of further progression of clarithromycin resistance in Russia to take additional measures to increase its effectiveness (detailed instruction of a patient and control over strict adherence to the prescribed regimen, prolonging the course up to 14 days; prescribing PPI at increased dose twice a day; the latest generation PPIs (rabeprazole and esomeprazole); adding bismuth tripotassium dicitrate (240 mg 2 times a day) to the standard triple therapy; adding cytoprotector rebamipide (100 mg 3 times a day) to the standard triple therapy; adding a probiotic with proven efficacy to the standard triple therapy within controlled studies).

Effectiveness of 7-day triple therapy with half-dose clarithromycin for the eradication of Helicobacter pylori without the A2143G and A2142G point mutations of the 23S rRNA gene in a high clarithromycin resistance area.

Tailored therapy has been widely used for patients with Helicobacter pylori (H. pylori) infection in South Korea. Herein, we evaluated the treatment outcomes of tailored clarithromycin-based triple therapy (TT) in patients infected with H. pylori. We enrolled 460 patients without A2142G and A2143G point mutations by dual priming oligonucleotide-based polymerase chain reaction who had taken TT and undergone the urease breath test to evaluate eradication in clinical practice. Eradication rates according to the treatment duration and dose of clarithromycin were analyzed. Among 460 patients (164 women, median age 63.0 years), 250 patients underwent TT with full-dose clarithromycin (TT-full CLA), and 216 patients underwent TT with half-dose clarithromycin (TT-half CLA). The eradication rates were 88.0% (220/250) in patients with TT-full CLA and 85.2% (179/210) in patients with TT-half CLA. In 250 patients with TT-full CLA, the eradication rates were 86.8% (33/38) in patients with 7-day TT-full CLA and 88.2% (187/212) in patients with 10-day or 14-day TT-full CLA (P = 0.788). In 210 patients with TT-half CLA, the eradication rates were 84.2% (139/165) in those with a 7-day TT-half CLA and 88.9% (40/45) in those with a 10-day or 14-day TT-half CLA (P = 0.436). For patients with H. pylori infection without A2142G and A2143G point mutations by DPO-PCR in clinical practice, treatment extension above 7-day TT with full CLA did not improve the eradication rates. Future studies on the treatment outcomes of TT-half CLA considering effectiveness and compliance are warranted.

A "new" option in Helicobacter pylori eradication: High-dose amoxicillin dual therapy outperforms bismuth quadruple therapy in a high dual resistance setting.

Currently, bismuth quadruple therapy (BQT) is indicated as a first-line treatment for Helicobacter pylori eradication in areas with high dual metronidazole and clarithromycin resistance, with its use being limited by its low tolerability and significant cost. A novel regimen with high-dose amoxicillin dual therapy (HDADT) has emerged as an alternative. The aim of this study was to compare the results of these two treatments on HP eradication. Prospective randomized study including 100 consecutive patients undergoing H.pylori eradication. Each patient was randomized (in a 1:1 ratio) to one group of treatment: BQT (bismuth 140 mg + metronidazole 125 mg + tetracycline 125 mg, four times a day, for 10 days) or HDADT (amoxicillin 1000 mg alternating with amoxicillin 500 mg, four times a day, for 14 days), both associated with esomeprazole 40 mg twice a day. The primary aim was to compare treatments' efficacies. Secondary aims were to assess symptoms persistence and tolerability. A total of 100 patients were included, 54% women, with a mean age of 55 ± 14 years. From these, five were lost to follow-up. Effective eradication proven by negative stool antigen test was significantly higher in patients randomized to HDADT when compared to BQT for both intention-to-treat (ITT) (96.2% vs. 81.4%; p= .022) and per-protocol (PP) (95.9% vs. 81%; p= .025) analysis. These differences were even more pronounced when only considering second line treatment (100% vs. 62.5%; p= .028). Side effects did not differ significantly between BQT and HDADT groups for both ITT (7.0% vs. 2.0%; p= .254) and PP (4.8% vs. 0%; p= .210) analysis. When compared to BQT, treatment with HDADT presented higher and near 100% efficacy in eradicating H.pylori, without differences in reported side effects or compliance. This treatment represents an important alternative for populations with increasing incidences of resistance to the currently recommended antibiotic regimens.

Helicobacter pylori resistance to clarithromycin and quinolones in patients with dyspepsia in Tuzla Canton, Bosnia and Herzegovina.

Aim To evaluate Helicobacter pylori (H. pylori) resistance to clarithromycin and quinolones in patients with dyspepsia in Tuzla Canton, Bosnia and Herzegovina, a region with no data on clarithromycin or quinolones resistance. Methods A prospective cross-sectional study was conducted at the Department of Gastroenterology and Hepatology at University Clinical Centre Tuzla between January 2021 and June 2022. The study included 99 patients who underwent esophagogastroduodenoscopy (EGDS) due to dyspepsia. In all patients biopsies were taken for rapid urease test (RUT) and histology findings, concomitantly with blood samples for IgG serology. All RUT positive patient samples were tested for clarithromycin and quinolones susceptibility with GenoType HelicoDr, a PCR method which detects point mutations in 23S rRNA and mutations in the gyrA gene. Results Out of 99 dyspeptic patients, 67 (67.7%) were serologically positive to H. pylori, 46 (46.4.%) were RUT positive, and 19 (19.2 %) had a positive histology finding. Antibiotic (AB) resistance was tested in the total of 46/99 (46.4%) patients. Resistance to clarithromycin was detected in 28.26% (13/46), quinolones resistance in 36.96% (17/46) , and resistance to both AB was detected in 8.69% (4/46) tested biopsies. Conclusions Due to high clarithromycin and quinolones resistance rates, we recommend the use of bismuth quadruple or non-bismuth concomitant quadruple therapy for H. pylori eradication in Tuzla Canton, Bosnia and Herzegovina.

Management of Helicobacter pylori infection.

Helicobacter pylori infection exhibits a wide disease spectrum ranging from asymptomatic gastritis, peptic ulcer disease, to gastric cancer. H. pylori can induce dysbiosis of gastric microbiota in the pathway of carcinogenesis and successful eradication can restore gastric homeostasis. Diagnostic testing and treatment for H. pylori infection is recommended in patients with active or past history of peptic ulcer, chronic dyspepsia, chronic non-steroidal anti-inflammatory drugs (NSAID) or aspirin use, precancerous gastric lesions, gastric cancer, mucosa-associated lymphoid tissue (MALT) lymphoma, family history of gastric cancer, family history of peptic ulcers, household family member having active H. pylori infection, iron deficiency anemia, idiopathic thrombocytopenic purpura, or vitamin B12 deficiency. Recommended first-line regimens for H. pylori eradication are classified according to clarithromycin resistance. In areas of high clarithromycin resistance (≥15%), we recommend 14-day concomitant therapy or 14-day bismuth quadruple therapy (BQT) as first-line regimen. In areas of low clarithromycin resistance (<15%), we recommend 14-day triple therapy or 14-day BQT as first-line treatment. Second-line regimens are 14-day levofloxacin triple therapy or 14-day BQT if BQT is not previously used. For patients with multiple treatment failure, antimicrobial susceptibility testing (AST) should be performed. If AST is not available, we recommend using antibiotics not previously used or for which resistance is unlikely, such as amoxicillin, tetracycline, bismuth, or furazolidone. High-dose potent proton pump inhibitor or vonoprazan is recommended to achieve adequate acid suppression. Probiotics can be used as an adjuvant treatment to reduce the side effects of antibiotics and enhance eradication rate.

The influence of gastric atrophy on Helicobacter pylori antibiotics resistance in therapy-naïve patients

BackgroundAntibiotic susceptibility of Helicobacter pylori to antibiotics may vary among different niches of the stomach. The progression of chronic H. pylori gastritis to atrophy changes intragastric physiology that may influence selection of resistant strains.AimTo study the antibiotic resistance of H. pylori taking the severity of atrophic gastritis in antrum and corpus into account.MethodsHelicobacter pylori-positive patients (n = 110, m = 32, mean age 52.6 ± 13.9 years) without prior H. pylori eradication undergoing upper gastrointestinal (GI) endoscopy for dyspeptic symptoms were included in a prospective study. Patients were stratified into three groups depending on the grade of atrophy: no atrophy (OLGA Stage 0), mild atrophy (OLGA Stage I–II) and moderate/severe atrophy (OLGA Stage III–IV). Two biopsies each from the antrum and the corpus and one from the angulus were taken and assessed according to the updated Sydney system. H. pylori strains were isolated from antrum and corpus biopsies and tested for antibiotic susceptibility (AST) for amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifampicin by the agar dilution methods. A Chi-square test of independence with a 95% confidence interval was used to detect differences in the proportion of patients with susceptible and resistant H. pylori strains.ResultsAmong 110 patients, primary clarithromycin resistance (R) was 30.0%, both in the antrum and corpus; metronidazole resistance accounted for 36.4 and 34.5% in the antrum and corpus; and levofloxacin was 19.1 and 22.7% in the antrum and corpus, respectively. Resistance rates to amoxicillin, tetracycline, and rifampicin were below 5%. Dual antibiotic resistance rate was 21.8%, and triple resistance rate was 9.1%. There was a significant difference in the resistance rate distribution in antrum (p < 0.0001) and corpus (p < 0.0001). With increasing severity of atrophy according to OLGA stages, there was a significant increase in clarithromycin-R and metronidazole-R.ConclusionIn treatment-naïve patients, antibiotic resistance and heteroresistance were related to the severity of atrophy. The high clarithromycin resistance in atrophic gastritis suggests that H. pylori antibiotic susceptibility testing should always be performed in this condition before selecting the eradication regimen.

Efficacy and safety of high-dose esomeprazole-amoxicillin dual therapy for Helicobacter pylori rescue treatment: a multicenter, prospective, randomized, controlled trial.

Background:High-dose dual therapy (HDDT) with proton pump inhibitors (PPIs) and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of high-dose PPI–amoxicillin dual therapy and bismuth-containing quadruple therapy for H. pylori rescue treatment.Methods:This was a prospective, randomized, multicenter, non-inferiority trial. Patients recruited from eight centers who had failed previous treatment were randomly (1:1) allocated to two eradication groups: HDDT (esomeprazole 40 mg and amoxicillin 1000 mg three times daily; the HDDT group) and bismuth-containing quadruple therapy (esomeprazole 40 mg, bismuth potassium citrate 220 mg, and furazolidone 100 mg twice daily, combined with tetracycline 500 mg three times daily; the tetracycline, furazolidone, esomeprazole, and bismuth [TFEB] group) for 14 days. The primary endpoint was the H. pylori eradication rate. The secondary endpoints were adverse effects, symptom improvement rates, and patient compliance.Results:A total of 658 patients who met the criteria were enrolled in this study. The HDDT group achieved eradication rates of 75.4% (248/329), 81.0% (248/306), and 81.3% (248/305) asdetermined by the intention-to-treat (ITT), modified intention-to-treat (MITT), and per-protocol (PP) analyses, respectively. The eradication rates were similar to those in the TFEB group: 78.1% (257/329), 84.2% (257/305), and 85.1% (257/302). The lower 95% confidence interval boundary (−9.19% in the ITT analysis, − 9.21% in the MITT analysis, and −9.73% in the PP analysis) was greater than the predefined non-inferiority margin of −10%, establishing a non-inferiority of the HDDT group vs. the TFEB group. The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group (11.1% vs. 26.8%, P < 0.001). Symptom improvement rates and patients’ compliance were similar between the two groups.Conclusions:Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy, with fewer adverse effects and good treatment compliance, suggesting HDDT as an alternative for H. pylori rescue treatment in the local region.Trial registration:Clinicaltrials.gov, NCT04678492.

7-day versus 14-day tegoprazan-based triple therapy to treat Helicobacter pylori infection: Real-world evidence.

Potassium-competitive acid blockers (P-CABs) can be used to eradicate Helicobacter pylori infection. We aimed to evaluate the impact of treatment duration (7 vs 14days) on successful H. pylori eradication with P-CAB-based triple therapy in Korea, where clarithromycin resistance rate is high. We retrospectively reviewed the data of patients who received first-line treatment for H. pylori infection with tegoprazan-based triple therapy (50mg tegoprazan+1000mg amoxicillin+500mg clarithromycin twice daily for 1 or 2weeks). The primary endpoint was the eradication rate in intention-to-treat (ITT) analysis. Of the 948 patients included in the study, 435 and 513 received 7-day and 14-day tegoprazan-based triple therapy, respectively. The eradication rate was higher in the 14-day therapy group than in the 7-day therapy group (ITT, 63.9%; 95% confidence interval [CI], 59.3-68.3%] vs 78.6% [95% CI, 74.9-81.9%], respectively, P<0.001; per-protocol, 70.5% [95% CI, 65.8-74.8%] vs 85.1% [81.7-88.1%], respectively, P<0.001). Overall adverse event rates did not differ between the two groups. Although six patients in the 14-day treatment group discontinued the prescribed medications due to adverse events, four of them (67%) discontinued the medication within 4days. The 14-day tegoprazan-based triple therapy showed a superior eradication rate and acceptable adverse events compared with the 7-day tegoprazan-based triple therapy. A 14-day treatment regimen may be required when H. pylori infection is treated with tegoprazan-based triple therapy in regions with high clarithromycin resistance.