Efficacies of Genotypic Resistance-Guided vs Empirical Therapy for Refractory Helicobacter pylori Infection

Taiwan Gastrointestinal Disease and Helicobacter Consortium

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background & Aims: We aimed to compare the efficacy of genotypic resistance–guided therapy vs empirical therapy for eradication of refractory Helicobacter pylori infection in randomized controlled trials. Methods: We performed 2 multicenter, open-label trials of patients with H pylori infection (20 years or older) failed by 2 or more previous treatment regimens, from October 2012 through September 2017 in Taiwan. The patients were randomly assigned to groups given genotypic resistance–guided therapy for 14 days (n = 21 in trial 1, n = 205 in trial 2) or empirical therapy according to medication history for 14 days (n = 20 in trial 1, n = 205 in trial 2). Patients received sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole, with levofloxacin, clarithromycin, or tetracycline (doxycycline in trial 1, tetracycline in trial 2) for another 7 days (all given twice daily) based on genotype markers of resistance determined from gastric biopsy specimens (group A) or empirical therapy according to medication history. Resistance-associated mutations in 23S ribosomal RNA or gyrase A were identified by polymerase chain reaction with direct sequencing. Eradication status was determined by 13C-urea breath test. The primary outcome was eradication rate. Results: H pylori infection was eradicated in 17 of 21 (81%) patients receiving genotype resistance–guided therapy and 12 of 20 (60%) patients receiving empirical therapy (P =.181) in trial 1. This trial was terminated ahead of schedule due to the low rate of eradication in patients given doxycycline sequential therapy (15 of 26 [57.7%]). In trial 2, H pylori infection was eradicated in 160 of 205 (78%) patients receiving genotype resistance–guided therapy and 148 of 205 (72.2%) patients receiving empirical therapy (P =.170), according to intent to treat analysis. The frequencies of adverse effects and compliance did not differ significantly between groups. Conclusions: Properly designed empirical therapy, based on medication history, is an acceptable alternative to genotypic resistance–guided therapy for eradication of refractory H pylori infection after consideration of accessibility, cost, and patient preference. ClinicalTrials.gov ID: NCT01725906.

Original languageEnglish
Pages (from-to)1109-1119
Number of pages11
JournalGastroenterology
Volume155
Issue number4
DOIs
Publication statusPublished - Oct 1 2018

Fingerprint

Helicobacter Infections
Helicobacter pylori
Pylorus
Therapeutics
Esomeprazole
Doxycycline
Genotype
Infection
Tetracycline
23S Ribosomal RNA
Levofloxacin
Breath Tests
Clarithromycin
Patient Preference
Amoxicillin
Metronidazole
Taiwan
Compliance
Urea
Stomach

Keywords

  • 23S rRNA
  • Gyrase A
  • Susceptibility Testing
  • Third-Line

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Efficacies of Genotypic Resistance-Guided vs Empirical Therapy for Refractory Helicobacter pylori Infection. / Taiwan Gastrointestinal Disease and Helicobacter Consortium.

In: Gastroenterology, Vol. 155, No. 4, 01.10.2018, p. 1109-1119.

Research output: Contribution to journalArticle

Taiwan Gastrointestinal Disease and Helicobacter Consortium. / Efficacies of Genotypic Resistance-Guided vs Empirical Therapy for Refractory Helicobacter pylori Infection. In: Gastroenterology. 2018 ; Vol. 155, No. 4. pp. 1109-1119.
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abstract = "Background & Aims: We aimed to compare the efficacy of genotypic resistance–guided therapy vs empirical therapy for eradication of refractory Helicobacter pylori infection in randomized controlled trials. Methods: We performed 2 multicenter, open-label trials of patients with H pylori infection (20 years or older) failed by 2 or more previous treatment regimens, from October 2012 through September 2017 in Taiwan. The patients were randomly assigned to groups given genotypic resistance–guided therapy for 14 days (n = 21 in trial 1, n = 205 in trial 2) or empirical therapy according to medication history for 14 days (n = 20 in trial 1, n = 205 in trial 2). Patients received sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole, with levofloxacin, clarithromycin, or tetracycline (doxycycline in trial 1, tetracycline in trial 2) for another 7 days (all given twice daily) based on genotype markers of resistance determined from gastric biopsy specimens (group A) or empirical therapy according to medication history. Resistance-associated mutations in 23S ribosomal RNA or gyrase A were identified by polymerase chain reaction with direct sequencing. Eradication status was determined by 13C-urea breath test. The primary outcome was eradication rate. Results: H pylori infection was eradicated in 17 of 21 (81{\%}) patients receiving genotype resistance–guided therapy and 12 of 20 (60{\%}) patients receiving empirical therapy (P =.181) in trial 1. This trial was terminated ahead of schedule due to the low rate of eradication in patients given doxycycline sequential therapy (15 of 26 [57.7{\%}]). In trial 2, H pylori infection was eradicated in 160 of 205 (78{\%}) patients receiving genotype resistance–guided therapy and 148 of 205 (72.2{\%}) patients receiving empirical therapy (P =.170), according to intent to treat analysis. The frequencies of adverse effects and compliance did not differ significantly between groups. Conclusions: Properly designed empirical therapy, based on medication history, is an acceptable alternative to genotypic resistance–guided therapy for eradication of refractory H pylori infection after consideration of accessibility, cost, and patient preference. ClinicalTrials.gov ID: NCT01725906.",
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T1 - Efficacies of Genotypic Resistance-Guided vs Empirical Therapy for Refractory Helicobacter pylori Infection

AU - Taiwan Gastrointestinal Disease and Helicobacter Consortium

AU - Liou, Jyh Ming

AU - Chen, Po Yueh

AU - Luo, Jiing Chyuan

AU - Lee, Ji Yuh

AU - Chen, Chieh Chang

AU - Fang, Yu Jen

AU - Yang, Tsung Hua

AU - Chang, Chi Yang

AU - Bair, Ming Jong

AU - Chen, Mei Jyh

AU - Hsu, Yao Chun

AU - Hsu, Wen Feng

AU - Chang, Chun Chao

AU - Lin, Jaw Town

AU - Shun, Chia Tung

AU - El-Omar, Emad M.

AU - Wu, Ming Shiang

AU - Liou, Jyh Ming

AU - Lee, Yi Chia

AU - Lin, Jaw Town

AU - Wu, Chun Ying

AU - Wu, Jeng Yih

AU - Chen, Ching Chow

AU - Lin, Chun Hung

AU - Fang, Yu Ren

AU - Bair, Ming Jong

AU - Luo, Jiing Chyuan

AU - Wu, Ming Shiang

AU - Cheng, Tsu Yao

AU - Tseng, Ping Huei

AU - Chiu, Han Mo

AU - Chang, Chun Chao

AU - Yu, Chien Chun

AU - Chiu, Min Chin

AU - Chen, Yen Nien

AU - Hu, Wen Hao

AU - Chou, Chu Kuang

AU - Tai, Chi Ming

AU - Lee, Ching Tai

AU - Wang, Wen Lun

AU - Chang, Wen Shiung

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Background & Aims: We aimed to compare the efficacy of genotypic resistance–guided therapy vs empirical therapy for eradication of refractory Helicobacter pylori infection in randomized controlled trials. Methods: We performed 2 multicenter, open-label trials of patients with H pylori infection (20 years or older) failed by 2 or more previous treatment regimens, from October 2012 through September 2017 in Taiwan. The patients were randomly assigned to groups given genotypic resistance–guided therapy for 14 days (n = 21 in trial 1, n = 205 in trial 2) or empirical therapy according to medication history for 14 days (n = 20 in trial 1, n = 205 in trial 2). Patients received sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole, with levofloxacin, clarithromycin, or tetracycline (doxycycline in trial 1, tetracycline in trial 2) for another 7 days (all given twice daily) based on genotype markers of resistance determined from gastric biopsy specimens (group A) or empirical therapy according to medication history. Resistance-associated mutations in 23S ribosomal RNA or gyrase A were identified by polymerase chain reaction with direct sequencing. Eradication status was determined by 13C-urea breath test. The primary outcome was eradication rate. Results: H pylori infection was eradicated in 17 of 21 (81%) patients receiving genotype resistance–guided therapy and 12 of 20 (60%) patients receiving empirical therapy (P =.181) in trial 1. This trial was terminated ahead of schedule due to the low rate of eradication in patients given doxycycline sequential therapy (15 of 26 [57.7%]). In trial 2, H pylori infection was eradicated in 160 of 205 (78%) patients receiving genotype resistance–guided therapy and 148 of 205 (72.2%) patients receiving empirical therapy (P =.170), according to intent to treat analysis. The frequencies of adverse effects and compliance did not differ significantly between groups. Conclusions: Properly designed empirical therapy, based on medication history, is an acceptable alternative to genotypic resistance–guided therapy for eradication of refractory H pylori infection after consideration of accessibility, cost, and patient preference. ClinicalTrials.gov ID: NCT01725906.

AB - Background & Aims: We aimed to compare the efficacy of genotypic resistance–guided therapy vs empirical therapy for eradication of refractory Helicobacter pylori infection in randomized controlled trials. Methods: We performed 2 multicenter, open-label trials of patients with H pylori infection (20 years or older) failed by 2 or more previous treatment regimens, from October 2012 through September 2017 in Taiwan. The patients were randomly assigned to groups given genotypic resistance–guided therapy for 14 days (n = 21 in trial 1, n = 205 in trial 2) or empirical therapy according to medication history for 14 days (n = 20 in trial 1, n = 205 in trial 2). Patients received sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole, with levofloxacin, clarithromycin, or tetracycline (doxycycline in trial 1, tetracycline in trial 2) for another 7 days (all given twice daily) based on genotype markers of resistance determined from gastric biopsy specimens (group A) or empirical therapy according to medication history. Resistance-associated mutations in 23S ribosomal RNA or gyrase A were identified by polymerase chain reaction with direct sequencing. Eradication status was determined by 13C-urea breath test. The primary outcome was eradication rate. Results: H pylori infection was eradicated in 17 of 21 (81%) patients receiving genotype resistance–guided therapy and 12 of 20 (60%) patients receiving empirical therapy (P =.181) in trial 1. This trial was terminated ahead of schedule due to the low rate of eradication in patients given doxycycline sequential therapy (15 of 26 [57.7%]). In trial 2, H pylori infection was eradicated in 160 of 205 (78%) patients receiving genotype resistance–guided therapy and 148 of 205 (72.2%) patients receiving empirical therapy (P =.170), according to intent to treat analysis. The frequencies of adverse effects and compliance did not differ significantly between groups. Conclusions: Properly designed empirical therapy, based on medication history, is an acceptable alternative to genotypic resistance–guided therapy for eradication of refractory H pylori infection after consideration of accessibility, cost, and patient preference. ClinicalTrials.gov ID: NCT01725906.

KW - 23S rRNA

KW - Gyrase A

KW - Susceptibility Testing

KW - Third-Line

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