title: Efficacy of genotypic resistance-guided sequential therapy in the third-line treatment of refractory Helicobacter pylori infection: a multicentre clinical trial.
abstract: OBJECTIVE
  The efficacy of sequential therapy and the applicability of genotypic resistance to guide the selection of antibiotics in the third-line treatment of Helicobacter pylori have not been reported. We aimed to assess the efficacy of genotypic resistance-guided sequential therapy in third-line treatment.
  
  
  METHODS
  Genotypic and phenotypic resistances were determined in patients who failed at least two eradication therapies by PCR with direct sequencing and agar dilution test, respectively. The patients were retreated with sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole plus clarithromycin, levofloxacin or tetracycline for another 7 days (all twice daily), according to genotypic resistance determined using gastric biopsy specimens. Eradication status was determined by the (13)C-urea breath test. Trial registered at clinicaltrials.gov (identifier: NCT01032655).
  
  
  RESULTS
  The overall eradication rate was 80.7% (109/135, 95% CI 73.3%-86.5%) in the intention-to-treat analysis. The presence of amoxicillin resistance (OR 6.83, 95% CI 1.62-28.86, P = 0.009) and prior sequential therapy (OR 4.77, 95% CI 1.315-17.3, P = 0.017), but not tetracycline resistance (tetracycline group), were associated with treatment failure. The eradication rates in patients who received clarithromycin-, levofloxacin- and tetracycline-based sequential therapies were 78.9% (15/19), 92.2% (47/51) and 71.4% (25/35) in strains susceptible to clarithromycin, levofloxacin and tetracycline, respectively.
  
  
  CONCLUSIONS
  A simple molecular method guiding sequential therapy can achieve a high eradication rate in the third-line treatment of refractory H. pylori infection.
authors.affiliation: Department of Internal Medicine,  National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei,  Taiwan.
authors.forename: Jyh-Ming
authors.initials: JM
authors.lastname: Liou
authors.forename: Chieh-Chang
authors.initials: CC
authors.lastname: Chen
authors.forename: Chi-Yang
authors.initials: CY
authors.lastname: Chang
authors.forename: Mei-Jyh
authors.initials: MJ
authors.lastname: Chen
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Fang
authors.forename: Ji-Yuh
authors.initials: JY
authors.lastname: Lee
authors.forename: Chien-Chuan
authors.initials: CC
authors.lastname: Chen
authors.forename: Shih-Jer
authors.initials: SJ
authors.lastname: Hsu
authors.forename: Yao-Chun
authors.initials: YC
authors.lastname: Hsu
authors.forename: Cheng-Hao
authors.initials: CH
authors.lastname: Tseng
authors.forename: Ping-Huei
authors.initials: PH
authors.lastname: Tseng
authors.forename: Lawrence
authors.initials: L
authors.lastname: Chang
authors.forename: Wen-Hsiung
authors.initials: WH
authors.lastname: Chang
authors.forename: Hsiu-Po
authors.initials: HP
authors.lastname: Wang
authors.forename: Chia-Tung
authors.initials: CT
authors.lastname: Shun
authors.forename: Jeng-Yih
authors.initials: JY
authors.lastname: Wu
authors.forename: Yi-Chia
authors.initials: YC
authors.lastname: Lee
authors.forename: Jaw-Town
authors.initials: JT
authors.lastname: Lin
authors.forename: Ming-Shiang
authors.initials: MS
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001944:Breath Tests; D016903:Drug Monitoring; D024881:Drug Resistance, Bacterial; D005260:Female; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D014508:Urea / Q000032:analysis
chemical_list: D000900:Anti-Bacterial Agents; D014508:Urea