Effectiveness of Helicobacter pylori Treatments According to Antibiotic Resistance.

INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance. METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included. RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results. DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.

Evaluation of a New Monoclonal Chemiluminescent Immunoassay Stool Antigen Test for the Diagnosis of Helicobacter pylori Infection: A Spanish Multicentre Study.

The stool antigen test (SAT) represents an attractive alternative for detection of Helicobacter pylori. The aim of this study was to assess the accuracy of a new SAT, the automated LIAISON® Meridian H. pylori SA based on monoclonal antibodies, compared to the defined gold standard 13C-urea breath test (UBT). This prospective multicentre study (nine Spanish centres) enrolled patients ≥18 years of age with clinical indication to perform UBT for the initial diagnosis and for confirmation of bacterial eradication. Two UBT methods were used: mass spectrometry (MS) including citric acid (CA) or infrared spectrophotometry (IRS) without CA. Overall, 307 patients (145 naïve, 162 with confirmation of eradication) were analysed. Using recommended cut-off values (negative SAT < 0.90, positive ≥ 1.10) the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 67%, 97%, 86%, 92% and 91%, respectively, obtaining an area under the receiver operating characteristic (ROC) curve (AUC) of 0.85. Twenty-eight patients, including seven false positives and 21 false negatives, presented a discordant result between SAT and UBT. Among the 21 false negatives, four of six tested with MS and 11 of 15 tested with IRS presented a borderline UBT delta value. In 25 discordant samples, PCR targeting H. pylori DNA was performed to re-assess positivity and SAT accuracy was re-analysed: sensitivity, specificity, positive predictive value, negative predictive value, accuracy and AUC were 94%, 97%, 86%, 99%, 97% and 0.96, respectively. The new LIAISON® Meridian H. pylori SA SAT showed a good accuracy for diagnosis of H. pylori infection.

Rescue Therapy with Furazolidone in Patients with at Least Five Eradication Treatment Failures and Multi-Resistant H. pylori infection.

Helicobacter pylori infection may persist after multiple eradication treatments. The aim of this study was to evaluate the efficacy and safety of a furazolidone-based rescue regimen in hyper-refractory patients. A unicentre, prospective study was designed. Patients in whom five or more treatments had consecutively failed were included. All patients had previously received bismuth and key antibiotics, such as amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifabutin, and had positive H. pylori culture, demonstrating resistance to clarithromycin, metronidazole, and levofloxacin. A quadruple regimen with furazolidone (200 mg), amoxicillin (1 g), bismuth (240 mg), and esomeprazole (40 mg) was prescribed twice a day for 14 days. Eradication was confirmed by the stool antigen test. Compliance was determined through questioning, and adverse effects using a questionnaire. Eight patients (mean age 56 years, 63% men, 38% peptic ulcer disease, 12% gastric cancer precursor lesions, and 50% functional dyspepsia) were included. Per-protocol and intention-to-treat eradication rates were 63%. Compliance was 100%. Adverse effects were reported in two (25%) patients, and all were mild. Even after five or more previous H. pylori eradication failures, and a multi-resistant infection, rescue treatment with furazolidone may be effective in approximately two-thirds of the cases, constituting a valid strategy after multiple previous eradication failures with key antibiotics such as clarithromycin, metronidazole, tetracycline, levofloxacin, and rifabutin.

Antibiotic Resistance Prevalence and Trends in Patients Infected with Helicobacter pylori in the Period 2013-2020: Results of the European Registry on H. pylori Management (Hp-EuReg).

Background: Bacterial antibiotic resistance changes over time depending on multiple factors; therefore, it is essential to monitor the susceptibility trends to reduce the resistance impact on the effectiveness of various treatments. Objective: To conduct a time-trend analysis of Helicobacter pylori resistance to antibiotics in Europe. Methods: The international prospective European Registry on Helicobacter pylori Management (Hp-EuReg) collected data on all infected adult patients diagnosed with culture and antimicrobial susceptibility testing positive results that were registered at AEG-REDCap e-CRF until December 2020. Results: Overall, 41,562 patients were included in the Hp-EuReg. Culture and antimicrobial susceptibility testing were performed on gastric biopsies of 3974 (9.5%) patients, of whom 2852 (7%) were naive cases included for analysis. The number of positive cultures decreased by 35% from the period 2013-2016 to 2017-2020. Concerning naïve patients, no antibiotic resistance was found in 48% of the cases. The most frequent resistances were reported against metronidazole (30%), clarithromycin (25%), and levofloxacin (20%), whereas resistances to tetracycline and amoxicillin were below 1%. Dual and triple resistances were found in 13% and 6% of the cases, respectively. A decrease (p < 0.001) in the metronidazole resistance rate was observed between the 2013-2016 (33%) and 2017-2020 (24%) periods. Conclusion: Culture and antimicrobial susceptibility testing for Helicobacter pylori are scarcely performed (<10%) in Europe. In naïve patients, Helicobacter pylori resistance to clarithromycin remained above 15% throughout the period 2013-2020 and resistance to levofloxacin, as well as dual or triple resistances, were high. A progressive decrease in metronidazole resistance was observed.

Bismuth quadruple regimen with tetracycline or doxycycline versus three-in-one single capsule as third-line rescue therapy for Helicobacter pylori infection: Spanish data of the European Helicobacter pylori Registry (Hp-EuReg).

BACKGROUND: Different bismuth quadruple therapies containing proton-pump inhibitors, bismuth salts, metronidazole, and a tetracycline have been recommended as third-line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin. AIM: To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole, and either tetracycline or doxycycline. METHODS: Sub-study with Spanish data of the "European Registry on H pylori Management" (Hp-EuReg), international multicenter prospective non-interventional Registry of the routine clinical practice of gastroenterologists. After previous failure with clarithromycin- and levofloxacin-containing therapies, patients receiving a third-line regimen with 10/14-day bismuth salts, metronidazole, and either tetracycline (BQT-Tet) or doxycycline (BQT-Dox), or single capsule (BQT-three-in-one) were included. Data were registered at AEG-REDCap database. Univariate and multivariate analyses were performed. RESULTS: Four-hundred and fifty-four patients have been treated so far: 85 with BQT-Tet, 94 with BQT-Dox, and 275 with BQT-three-in-one. Average age was 53 years, 68% were women. Overall modified intention-to-treat and per-protocol eradication rates were 81% (BQT-Dox: 65%, BQT-Tet: 76%, BQT-three-in-one: 88%) and 82% (BQT-Dox: 66%, BQT-Tet: 77%, BQT-three-in-one: 88%), respectively. By logistic regression, higher eradication rates were associated with compliance (OR = 2.96; 95% CI = 1.01-8.84) and no prior metronidazole use (OR = 1.96; 95% CI = 1.15-3.33); BQT-three-in-one was superior to BQT-Dox (OR = 4.46; 95% CI = 2.51-8.27), and BQT-Tet was marginally superior to BQT-Dox (OR = 1.67; 95% CI = 0.85-3.29). CONCLUSION: Third-line H pylori eradication with bismuth quadruple treatment (after failure with clarithromycin and levofloxacin) offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and those taking 10-day BQT-three-in-one or 14-day BQT-Tet. Doxycycline seems to be less effective and therefore should not be recommended.