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Susceptibility-guided therapy for Helicobacter pylori infection treatment failures.

ABSTRACT: Background:Empirical therapy of Helicobacter pylori frequently results in treatment failure due to unrecognized antimicrobial resistance. The aim of this study was to investigate the effectiveness of susceptibility-guided therapy for rescue treatment of H. pylori infection in China. Methods:This was a prospective study of consecutive 200 patients infected with H. pylori with one or more treatment failures. The therapy chosen was susceptibility based using the most effective, best-tolerated regimens first and a locally proven, reliably effective regimen for multidrug-resistant infections. All patients received 14-day triple therapy, i.e. esomeprazole 20?mg and amoxicillin 1?g twice a day plus clarithromycin 500?mg twice a day, metronidazole 400?mg twice a day, or levofloxacin 500?mg daily, or, for multidrug-resistant infections, amoxicillin-containing bismuth quadruple therapy with esomeprazole 20?mg twice a day, bismuth 220?mg twice a day, amoxicillin 1?g three times a day, and metronidazole 400?mg four times a day. Antibiotic resistance was determined by agar dilution. Results:The eradication rate of susceptibility-guided therapy overall was 94.5% (189/200, 95% confidence interval: 90.4-97.2%). Around 28% (56/200) of patients carried strains susceptible to one of the tested antibiotics and were prescribed the triple therapy. A total of 144 multidrug-resistant patients received bismuth quadruple therapy. The eradication rates were all greater than 90%, i.e. 91.7% (11/12), 92.3% (12/13), and 93.5% (29/31) in those who received clarithromycin, metronidazole, and levofloxacin-containing triple therapy and 95.1% (137/144) for the bismuth quadruple therapy. There were no differences in eradication rates between the subgroups. Conclusions:Although susceptibility-guided therapy proved high efficacious despite the high proportion of multidrug-resistant strains, the strategy suggested the best approach for this population would be empirical amoxicillin-containing bismuth quadruple therapy. ClinicalTrials.gov identifier: NCT03413020.

SUBMITTER: Yu L

PROVIDER: S-EPMC6734621 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Susceptibility-guided therapy for <i>Helicobacter pylori</i> infection treatment failures.

Yu Lou L Luo Laisheng L Long Xiaohua X Liang Xiao X Ji Yingjie Y Chen Qi Q Song Yanyan Y Li Xiaobo X Graham David Y DY Lu Hong H

Therapeutic advances in gastroenterology 20190909

<h4>Background</h4>Empirical therapy of <i>Helicobacter pylori</i> frequently results in treatment failure due to unrecognized antimicrobial resistance. The aim of this study was to investigate the effectiveness of susceptibility-guided therapy for rescue treatment of <i>H. pylori</i> infection in China.<h4>Methods</h4>This was a prospective study of consecutive 200 patients infected with <i>H. pylori</i> with one or more treatment failures. The therapy chosen was susceptibility based using the ...[more]

PMID: 31523279

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Project description:BackgroundTreating Helicobacter pylori infection according to antibiotic resistance has been frequently recommended. However, information on its real effectiveness is scarce.AimThe aim of this study is to perform a meta-analysis comparing empirical vs. susceptibility-guided treatment of H. pylori.MethodsSelection of studies: Studies comparing empirical versus susceptibility-guided treatment were selected. Search strategy: electronic and manual up to August 2021. Data synthesis: by intention-to-treat (random-effects model).ResultsOverall, 54 studies were included (6,705 patients in the susceptibility-guided group and 7,895 in the empirical group). H. pylori eradication rate was 86 vs. 76%, respectively (RR: 1.12; 95% CI: 1.08-1.17; I 2: 83%). Similar results were found when only RCTs were evaluated (24 studies; RR: 1.16; 95% CI: 1.11-1.22; I 2: 71%) and when susceptibility testing was assessed by culture (RR: 1.12; 95% CI: 1.06-1.18) or PCR (RR: 1.14; 95% CI: 1.05-1.23). For first-line treatments (naïve patients; 30 studies), better efficacy results were obtained with the susceptibility-guided strategy (RR: 1.15; 95% CI: 1.11-1.20; I 2: 79%). However, for empirical first-line quadruple regimens, in particular (both with and without bismuth, excluding the suboptimal triple therapies), not based on CYP2C19 gene polymorphism, no differences in efficacy were found compared with the susceptibility-guided group (RR: 1.04; 95% CI: 0.99-1.09); this lack of difference was confirmed in RCTs (RR: 1.05; 95% CI: 0.99-1.12). For rescue therapies (13 studies, most 2nd-line), similar results were demonstrated for both strategies, including all studies (RR: 1.09; 95% CI: 0.97-1.22; I 2: 82%) and when only RCTs were considered (RR: 1.15; 95% CI: 0.97-1.36).ConclusionThe benefit of susceptibility-guided treatment over empirical treatment of H. pylori infection could not be demonstrated, either in first-line (if the most updated quadruple regimens are prescribed) or in rescue therapies.

Project description:In this review, we discuss the problem of antibiotic resistance, heteroresistance, the utility of cultures and antibiotic susceptibility tests in Helicobacter pylori (Hp) eradication, as well as the updated treatment strategies for this infection. The prevalence of antibiotic resistance is increasing all over the world, especially for metronidazole and clarithromycin, because of their heavy use in some geographical areas. Heteroresistance (simultaneous presence of both susceptible and resistant strains in different sites of a single stomach) is another important issue, as an isolate could be mistakenly considered susceptible if a single biopsy is used for antimicrobial tests. We also examined literature data regarding eradication success rates of culture-guided and empiric therapies. The empiric therapy and the one based on susceptibility testing, in Hp eradication, may depend on several factors such as concomitant diseases, the number of previous antibiotic treatments, differences in bacterial virulence in individuals with positive or negative cultures, together with local antibiotic resistance patterns in real-world settings. Updated treatment strategies in Hp infection presented in the guidelines of the Toronto Consensus Group (2016) are reported. These suggest to prolong eradication therapy up to 14 days, replacing the old triple therapy with a quadruple therapy based on proton pump inhibitor (PPI), bismuth, metronidazole, and tetracycline for most of the patients, or as an alternative quadruple therapy without bismuth, based on the use of PPI, amoxicillin, metronidazole, and clarithromycin. The new drug vonoprazan, a first-in-class potassium-competitive acid blocker recently approved in Japan, is also considered to be a promising solution for Hp eradication, even for clarithromycin-resistant strains. Furthermore, there is growing interest in finding new therapeutic strategies, such as the development of vaccines or the use of natural resources, including probiotics, plants, or nutraceuticals.

Project description:BackgroundNew treatment strategies are required against infections caused by Helicobacter pylori, which grows increasingly resistant to antibiotics. Polymerase chain reaction-based methods for antibiotic susceptibility testing are available for detecting H. pylori-specific mutations that confer resistance to clarithromycin and levofloxacin. Several meta-analyses have compared eradication rates for susceptibility-guided versus empirical therapy for H. pylori treatment; however, all have significant limitations and high heterogeneity, and the results are contradictory. The main objective of this trial is to assess whether a sequential strategy based on molecular susceptibility testing-guided therapy for H. pylori has a better eradication rate than empirical therapy.MethodsThis trial is designed as a prospective, randomised, open-label, active-controlled and single-centre study. Men and women who are H. pylori-positive, naïve to treatment, and aged 18-65 years will be recruited. A total of 500 participants will be randomised to receive either empirical therapy or a susceptibility-guided sequential strategy. Bismuth quadruple therapy will be the empirical first-line therapy, and in case of failure, high-dose dual (proton-pump inhibitor + amoxicillin) treatment will be the rescue therapy. For the susceptibility-guided sequential strategy, regimen selection will be based on H. pylori susceptibility to clarithromycin (first-line) and levofloxacin (rescue). A first-line treatment of clarithromycin triple therapy will be selected for clarithromycin-sensitive strains. For clarithromycin resistance, a high-dose dual therapy will be selected. During the rescue treatment, a levofloxacin quadruple regimen will be selected for levofloxacin-sensitive strains, and a furazolidone quadruple regimen will be selected for others. The primary outcome is the first-line eradication rate in both groups, and the overall (including first and rescue therapies) H. pylori eradication rate in both groups is one of the secondary outcomes. The eradication rates of H. pylori will be analysed by intention-to-treat analysis, modified intention-to-treat analysis, and per-protocol analysis.DiscussionThis randomised controlled trial will provide objective and valid evidence about the value of polymerase chain reaction-based molecular methods for antibiotic susceptibility testing in guiding H. pylori eradication.Trial registrationClinicaltrials.gov NCT05549115. Released on 18 September 2022. First posted on 22 September 2022. Enrolment of the first participant on 20 September 2022. The study is retrospectively registered.

Project description:BackgroundAlthough the Maastricht VI/Florence consensus report recommended high-dose proton pump inhibitor-amoxicillin dual therapy as possible rescue therapy for Helicobacter pylori infection, clinical evidence of its efficacy was lacking.ObjectivesTo compare the efficacy, safety, patient compliance, and cost between high-dose dual therapy (HDDT) and culture-based susceptibility-guided therapy (CB-SGT) as a rescue regimen for H. pylori infection.DesignA single-center, open-label, randomized controlled clinical trial.MethodsIn all, 146 patients with a history of eradication failure were enrolled and randomly assigned to receive HDDT or CB-SGT. HDDT consisted of esomeprazole 20 mg and amoxicillin 750 mg, both given four times per day (qid). CB-SGT consisted of esomeprazole 20 mg twice daily (bid), amoxicillin 1000 mg bid plus clarithromycin 500 mg bid, metronidazole 400 mg bid, or levofloxacin 500 mg daily (qd) for sensitive patients, in that order. For patients with triple resistance, a bismuth-containing regimen with a high dose of metronidazole was chosen, including esomeprazole 20 mg bid, bismuth 220 mg bid, amoxicillin 1000 mg bid, and metronidazole 400 mg qid. All regimens were given for 14 days.ResultsThe eradication H. pylori rates achieved with HDDT in the intention-to-treat (ITT), per-protocol, and modified ITT analyses were all 84.9% [62/73, 95% confidence interval (CI): 76.5-93.9%], compared with 83.6% (61/73, 95% CI: 74.9-92.3%), 84.7% (61/72, 95% CI: 76.2-93.2%), and 84.7% (61/72, 95% CI: 76.2-93.2%) with CB-SGT, respectively. For patients with CYP2C19 polymorphisms of intermediate/poor metabolizers, the eradication rates of HDDT and CB-SGT were 90.70% (39/43, 95% CI: 77.86-97.41%) and 84.21% (32/38, 95% CI: 68.75-93.98%), respectively. The difference between groups was 6.49% (95% CI: -8.00% to 20.97%), and the non-inferiority p value was 0.0128. For patients with a treatment interval of more than 3 months, the eradication rates of the two regimens reached 88.71% (95% CI: 78.11-95.34%) and 71.97% (95% CI: 70.02-90.64%). The difference between groups was 6.74% (95% CI: -5.71% to 19.20%), with a non-inferiority p value of 0.0042. Patient adherence was high in both groups. The HDDT had a lower cost and rate of side effects (p < 0.001) compared with CB-SGT.ConclusionsHDDT can reach an eradication rate of 85% in treatment-experienced patients of H. pylori infection and 91% in patients with CYP2C19 polymorphisms of intermediate/poor metabolizers, with good compliance, lower side effects and costs, and less use of antibiotics. In conclusion, HDDT offers an effective rescue regimen for H. pylori infection.RegistrationThis clinical trial was registered at the Chinese Clinical Trail Registry (trail registration number: ChiCTR1900025044).

Project description:Antibiotics resistance in Helicobacter pylori (H. pylori) is the major factor for eradication failure. Molecular tests including fluorescence in situ hybridization, PCR-restriction fragment length polymorphism, and dual priming oligonucleotide-PCR (DPO-PCR) play critical roles in the detection of antibiotic susceptibility; however, limited knowledge is known about application of multiple genetic analysis system (MGAS) in the area of H. pylori identification and antibiotics resistance detection.The aim of this study is to determine the antibiotics resistance using different molecular tests and evaluate the treatment outcomes of E-test-based genotypic resistance.A total of 297 patients with dyspepsia complaint were recruited for gastroscopies. Ninety patients with H. pylori culture positive were randomly divided into 2 groups (test group and control group). E-test, general PCR, and MGAS assay were performed in test group. Patients in control group were treated with empirical therapy (rabeprazole + bismuth potassium citrate + amoxicillin [AMX] + clarithromycin [CLR]), whereas patients in test group received quadruple therapy based on E-test results twice daily for 14 consecutive days. The eradication effect of H. pylori was confirmed by C-urea breath test after at least 4 weeks when treatment was finished.Rapid urease test showed 46.5% (128/297) patients with H. pylori infection, whereas 30.3% (90/297) patients were H. pylori culture positive. E-test showed that H. pylori primary resistance rate to CLR, AMX, metronidazole, tetracycline, and levofloxacin (LVX) was 40.0% (18/45), 4.4% (2/45), 53.3% (24/45), 0% (0/45), and 55.6% (25/45), respectively. In addition, there are many multidrug resistant (MDR) phenotypes, and the MDR strains have higher minimum inhibitory concentration than their single-drug resistant counterparts. Considering E-test as the reference test, the sensitivities of general PCR and MGAS in detecting CLR resistance were 83.3% (15/18) and 94.4% (17/18), whereas in detecting LVX resistance were 100% (25/25) and 83.3% (15/18), respectively. Finally, the eradication rate in test group was significantly higher than that in control group as demonstrated by intention-to-treat analysis and per-protocol analysis.MGAS is a promising assay for H. pylori identification and antibiotic susceptibility testing. Phenotypic resistance-guided quadruple therapy showed a high efficacy in treating patients with H. pylori infection.

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Susceptibility-guided therapy for Helicobacter pylori infection treatment failures.

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Susceptibility-guided therapy for <i>Helicobacter pylori</i> infection treatment failures.

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