Genetic Markers of Helicobacter pylori Resistance to Clarithromycin and Levofloxacin in Moscow, Russia.

The Maastricht VI/Florence consensus recommends, as one of the measures to enhance the efficacy of Helicobacter pylori infection eradication, a personalized treatment approach involving the selection of an antimicrobial agent based on the pre-determined resistance of H. pylori. To address the need to develop test systems for personalized drug selection, this study was designed to analyze the molecular resistance of H. pylori using a newly developed Sanger sequencing test platform. The characteristics of the test system were determined on 25 pure culture samples of H. pylori with known resistance. Sensitivity and specificity for detecting resistance to clarithromycin was 100% and those to levofloxacin were 93% and 92%, respectively. The test system has been tested in real clinical practice on 112 H. pylori-positive patients who had not previously received proton pump inhibitors (PPIs) or antibacterial drugs. Mutations indicating resistance to clarithromycin were found in 27 (24%) samples and those indicating resistance to levofloxacin were found in 26 (23%) samples. Double resistance was observed in 16 (14%) samples. The most common mutations leading to clarithromycin resistance were 2143G and 2142G and to levofloxacin resistance-261A and 271A in the gyrA gene, which account for 69% of all identified genetic determinants in levofloxacin-resistant bacteria. Thus, a personalized approach to the selection of H. pylori eradication therapy based on the detection of bacterial resistance before prescribing first-line therapy could help to avoid the prescription of ineffective H. pylori eradication therapies and, overall, contribute to the control of antibiotic resistance of H. pylori.

Helicobacter pylori Antibiotic Resistance: Molecular Basis and Diagnostic Methods.

Helicobacter pylori is one of the most common cause of human infections. Infected patients develop chronic active gastritis in all cases, which can lead to peptic ulcer, atrophic gastritis, gastric cancer and gastric MALT-lymphoma. The prevalence of H. pylori infection in the population has regional characteristics and can reach 80%. Constantly increasing antibiotic resistance of H. pylori is a major cause of treatment failure and a major problem. According to the VI Maastricht Consensus, two main strategies for choosing eradication therapy are recommended: individualized based on evaluating sensitivity to antibacterial drugs (phenotypic or molecular genetic method) prior to their appointment, and empirical, which takes into account data on local H. pylori resistance to clarithromycin and monitoring effectiveness schemes in the region. Therefore, the determination of H. pylori resistance to antibiotics, especially clarithromycin, prior to choosing therapeutic strategy is extremely important for the implementation of these treatment regimens.

Adverse Event Profile During the Treatment of Helicobacter pylori: A Real-World Experience of 22,000 Patients From the European Registry on H. pylori Management (Hp-EuReg).

INTRODUCTION: The safety of Helicobacter pylori eradication treatments and to what extent adverse events (AEs) influence therapeutic compliance in clinical practice are hardly known. Our aim was to assess the frequency, type, intensity, and duration of AEs, and their impact on compliance, for the most frequently used treatments in the "European Registry on Helicobacter pylori management." METHODS: Systematic prospective noninterventional registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H. pylori infection in routine clinical practice. All prescribed eradication treatments and their corresponding safety profile were recorded. AEs were classified depending on the intensity of symptoms as mild/moderate/severe and as serious AEs. All data were subject to quality control. RESULTS: The different treatments prescribed to 22,492 patients caused at least 1 AE in 23% of the cases; the classic bismuth-based quadruple therapy was the worst tolerated (37% of AEs). Taste disturbance (7%), diarrhea (7%), nausea (6%), and abdominal pain (3%) were the most frequent AEs. The majority of AEs were mild (57%), 6% were severe, and only 0.08% were serious, with an average duration of 7 days. The treatment compliance rate was 97%. Only 1.3% of the patients discontinued treatment due to AEs. Longer treatment durations were significantly associated with a higher incidence of AEs in standard triple, concomitant, bismuth quadruple, and levofloxacin triple or quadruple therapies. DISCUSSION: Helicobacter pylori eradication treatment frequently induces AEs, although they are usually mild and of limited duration. Their appearance does not interfere significantly with treatment compliance.

Dynamics of antimicrobial resistance of Helicobacter pylori isolates in the Smolensk region of Russian Federation.

BACKGROUND: Efficacy of Helicobacter pylori eradication therapy depends on the chance of having a resistant H. pylori strain, which is ultimately related to the local antimicrobial resistance epidemiology. AIM: To assess H. pylori resistance to clarithromycin, amoxicillin, metronidazole, levofloxacin, and tetracycline in adult patients in the Smolensk region of Russian Federation over a 9-year period. MATERIALS AND METHODS: Biopsy samples were taken from the gastric antrum and body of 573 and 210 patients with dyspepsia symptoms and positive rapid urease test during esophagogastroduodenoscopy in 2015-2017 and 2009-2010, respectively. Antimicrobial susceptibility testing was performed for clarithromycin, amoxicillin, metronidazole, levofloxacin, and tetracycline by the agar dilution method. RESULTS: A total of 143 strains of H. pylori isolated during 2015-2017 and 133 strains isolated during 2009-2010 were tested. Culture success rates were 30% vs 64% for the two periods. Over the 2015-2017, the prevalence of resistance to clarithromycin was 6.3%, to amoxicillin 1.4%, to metronidazole 23.8%, to levofloxacin 24.5%, and to tetracycline 0.7%. Over the 2009-2010, the corresponding resistance rates were 5.3%, 4.5%, 3.8%, 8.3%, and 0%, respectively. There were no significant increases in resistance to clarithromycin, amoxicillin, and tetracycline (P > 0.05) over the 9 years period. Significant increase in resistance to levofloxacin (8.3% in 2009-2010% vs 24.5% in 2015-2017, P < 0.01) and metronidazole (3.8% in 2009-2010% vs 23.8% in 2015-2017, P < 0.01) was observed. CONCLUSIONS: H. pylori resistance to clarithromycin remained low in the Smolensk region of Russian Federation between 2009 and 2017. Resistance to levofloxacin and metronidazole increased between 2009 and 2017.