title: Heteroresistance of Helicobacter pylori from the same patient prior to antibiotic treatment.
abstract: Antibiotic resistance among Helicobacter pylori strains has been increasing worldwide and has affected the efficacy of current treatments. The aim of this study was to evaluate whether treatment failure was due to the presence of antibiotic-susceptible and -resistant H. pylori simultaneously within the same host before eradication. In order to discover H. pylori with antibiotic heteroresistance in the same patient, we examined the antibiotic susceptibility of H. pylori isolated from 412 patients without H. pylori eradication. The E-test was used to determine the minimal inhibitory concentration of these strains. The results showed 19 (4.6%) of patients harbored antibiotic heteroresistant H. pylori, resistant to levofloxacin (5/19), clarithromycin (1/19) and metronidazole (16/19). Among them, three patients' isolates showed heteroresistance to two antibiotics. The genetic diversity of each isolate was evaluated by random amplified polymorphic DNA PCR and the results showed that only 1 patient' isolate (5.3%) had a different pattern while the others showed identical or similar fingerprinting patterns. Mutations in the genes responsible for antibiotic resistance were investigated by direct sequencing and compared between strains within each pair. All 5 levofloxacin-resistant isolates had mutations in GyrA at the QRDR region (N87 or D91). Strain 1571R with clarithromycin resistance had a A2042G substitution in its 23S rRNA. There were 15 metronidazole-resistant strains (100%) with isogenic variation of RdxA, and 6 strains (40%) contained FrxA variation (excluded pair 1159). These results suggest that the treatment failure of heteroresistant H. pylori mostly develops from high genomic variation of pre-existing strains through long term evolution rather than mixed infection with different strains.
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Cheng-Yen
authors.initials: CY
authors.lastname: Kao
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ai-Yun
authors.initials: AY
authors.lastname: Lee
authors.affiliation: Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ay-Huey
authors.initials: AH
authors.lastname: Huang
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Pin-Yi
authors.initials: PY
authors.lastname: Song
authors.affiliation: Department of Pediatrics, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yao-Jong
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shew-Meei
authors.initials: SM
authors.lastname: Sheu
authors.affiliation: Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Bor-Shyang
authors.initials: BS
authors.lastname: Sheu
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: jjwu@mail.ncku.edu.tw.
authors.forename: Jiunn-Jong
authors.initials: JJ
authors.lastname: Wu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D024881:Drug Resistance, Bacterial; D014644:Genetic Variation; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology*; D016480:Helicobacter pylori / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009601:Nitroreductases / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D009601:Nitroreductases; C476646:RdxA protein, Helicobacter pylori
keywords: Antibiotic; Helicobacter pylori; Heteroresistance; Treatment failure