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Antibiotic Resistance and Therapy Outcome in H. pylori Eradication Failure Patients.

ABSTRACT: Helicobacter pylori (H. pylori) eradication fails in a definite amount of patients despite one or more therapeutic attempts. Curing these patients is progressively more difficult, due to development of antibiotic resistance. Current guidelines suggest testing antibiotic susceptibility in H. pylori isolates following two therapeutic attempts. AIM:to evaluate the development of antibiotic resistance, MIC values trends and therapeutic outcomes in patients who failed at least one H. pylori eradication therapy. METHODS:consecutive patients, referred to perform upper gastrointestinal endoscopy (UGIE) to our Unit from January 2009 to January 2019 following at least one therapeutic attempt were considered. Bacterial resistance towards clarithromycin, metronidazole and levofloxacin was tested. Patients received either a susceptibility-guided therapy or Pylera®. RESULTS:a total of 1223 patients were H. pylori positive, and antibiotic susceptibility was available for 1037. The rate of antibiotic resistance and MIC values significantly increased paralleling the number of previous therapeutic attempts. Eradication rates of antibiogram-tailored therapies remained stable, except for the sequential therapy if used as a third line. As a rescue treatment, the Pylera® therapy achieved cure rates comparable to those of the other culture-guided therapies. CONCLUSIONS:A significant increase in the secondary resistance towards the three tested antibiotics was observed, both as rate and MIC values, in correlation with the number of therapy failures. These findings should be considered when administering an empirical second-line therapy. Pylera® therapy eradication rates are comparable to culture-tailored therapies.

SUBMITTER: Saracino IM

PROVIDER: S-EPMC7175201 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Antibiotic Resistance and Therapy Outcome in <i>H. pylori</i> Eradication Failure Patients.

Saracino I M IM Pavoni M M Zullo A A Fiorini G G Saccomanno L L Lazzarotto T T Cavallo R R Antonelli G G Vaira D D

Antibiotics (Basel, Switzerland) 20200313 3

<i>Helicobacter pylori</i> (<i>H. pylori</i>) eradication fails in a definite amount of patients despite one or more therapeutic attempts. Curing these patients is progressively more difficult, due to development of antibiotic resistance. Current guidelines suggest testing antibiotic susceptibility in <i>H. pylori</i> isolates following two therapeutic attempts.<h4>Aim</h4>to evaluate the development of antibiotic resistance, MIC values trends and therapeutic outcomes in patients who failed at l ...[more]

PMID: 32183165

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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.

Project description:Background:The efficacy and applicability of molecular testing to guide the selection of antibiotics in triple Helicobacter pylori (H. pylori) eradication regimens have not been reported. We tested a 7-day, genotypic resistance-guided triple H. pylori eradication therapy in a high-resistance setting. Methods:Consecutive dyspeptic patients with H. pylori infection were prospectively enrolled. Genotypic resistances to clarithromycin (23SrRNA mutations) and fluoroquinolones (gyrA mutations) were determined from gastric biopsy specimens using a commercially available molecular assay (GenoTypeâ HelicoDR). A tailored genotypic resistance-guided 7-day triple therapy comprised esomeprazole, amoxicillin, and either clarithromycin (wild-type 23SrRNA), levofloxacin (23SrRNA mutated/wild-type gyrA) or rifabutin (both 23SrRNA/gyrA mutated). H. pylori eradication was confirmed by 13C-urea breath test. Results:Of 148 subjects screened, 51 patients were enrolled (male/female: 27/24, mean age: 50.7±11.4 years, treatment-naïve/-experienced: 32/19). The molecular kit was easily implemented, allowing for rapid (within 24 h) and relatively inexpensive determination of H. pylori resistance (clarithromycin: 47.1%, fluoroquinolones: 15.7%, dual clarithromycin/fluoroquinolones: 7.8%). For patients who received clarithromycin-, levofloxacin- and rifabutin-containing triple therapy, the respective eradication rates were 24/27, 20/20, and 2/4 by intention-to-treat (ITT); and 24/24, 19/19 and 2/3 by per-protocol (PP) analysis. Overall eradication rates were 90.2% (95% confidence interval [CI] 77.8-96.3%) by ITT and 97.8% (95%CI 87-99.8%) by PP analysis, showing no significant difference between treatment-naïve and -experienced patients (ITT: 87.5% vs. 94.7%, P=0.64; PP: 96.4% vs. 100%, respectively, P=1.00). Conclusions:Regardless of prior treatment history, a genotypic resistance-guided 7-day triple therapy, based on a simple molecular assay, achieved a high H. pylori eradication rate.

Dataset Information

Antibiotic Resistance and Therapy Outcome in H. pylori Eradication Failure Patients.

Publications

Antibiotic Resistance and Therapy Outcome in <i>H. pylori</i> Eradication Failure Patients.

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