title: Genotypic resistance in Helicobacter pylori strains correlates with susceptibility test and treatment outcomes after levofloxacin- and clarithromycin-based therapies.
abstract: The accuracy of genotypic resistance to levofloxacin (gyrA mutations) and its agreement with treatment outcomes after levofloxacin-based therapy have not been reported. We aimed to assess the correlation. Helicobacter pylori strains isolated from patients who received levofloxacin-based and clarithromycin-based triple therapies in a previous randomized trial were analyzed for point mutations in gyrA and 23S rRNA. PCR followed by direct sequencing was used to assess the gyrA and 23S rRNA mutations. An agar dilution test was used to determine the MICs of clarithromycin and levofloxacin. We found that the agreement between genotypic and phenotypic resistance to levofloxacin was best when the MIC breakpoint was >1 μg/ml (kappa coefficient, 0.754). The eradication rates in patients with and without gyrA mutations were 41.7% and 82.7%, respectively (P = 0.003). The agreement between genotypic and phenotypic resistance to clarithromycin was best when the MIC breakpoint was >2 μg/ml (kappa, 0.694). The eradication rates in patients with and without 23S rRNA mutations were 7.7% and 93.5%, respectively (P < 0.001). The agreements (kappa coefficient) between therapeutic outcomes after clarithromycin-based triple therapy and genotypic and phenotypic resistance were 0.671 and 0.356, respectively. The agreements (kappa coefficient) between therapeutic outcomes after levofloxacin-based triple therapy and genotypic and phenotypic resistance were 0.244 and 0.190, respectively. In conclusion, gyrA and 23S rRNA mutations in H. pylori strains appeared to be better markers than phenotypic resistance in the prediction of treatment outcomes. The optimal breakpoints for levofloxacin and clarithromycin resistance appeared to be >1 μg/ml and >2 μg/ml, respectively.
authors.affiliation: Departmentsof 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: Chi-Yang
authors.initials: CY
authors.lastname: Chang
authors.forename: Wang-Huei
authors.initials: WH
authors.lastname: Sheng
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Wang
authors.forename: Mei-Jyh
authors.initials: MJ
authors.lastname: Chen
authors.forename: Yi-Chia
authors.initials: YC
authors.lastname: Lee
authors.forename: Hsu-Wei
authors.initials: HW
authors.lastname: Hung
authors.forename: Hung
authors.initials: H
authors.lastname: Chian
authors.forename: San-Chun
authors.initials: SC
authors.lastname: Chang
authors.forename: Ming-Shiang
authors.initials: MS
authors.lastname: Wu
authors.forename: Jaw-Town
authors.initials: JT
authors.lastname: Lin
mesh_terms: D000328:Adult; D017291:Clarithromycin / Q000627:therapeutic use*; D027081:DNA Gyrase / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005260:Female; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015242:Ofloxacin / Q000627:therapeutic use*; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D012338:RNA, Ribosomal, 23S; D064704:Levofloxacin; D015242:Ofloxacin; D027081:DNA Gyrase; D017291:Clarithromycin