title: Comparative in vitro antimicrobial susceptibility and synergistic activity of antimicrobial combinations against Helicobacter pylori isolates in Taiwan.
abstract: BACKGROUND
  Antimicrobial resistance is a major determinant of Helicobacter pylori treatment failures. We conducted a population-based survey to monitor changing antimicrobial susceptibility of H. pylori isolates in Taiwan, with a focus on combinatorial effects of synergism and the influence of acidity.
  
  
  METHODS
  H. pylori isolates from endoscopic specimens taken from patients enrolled at two medical centers were obtained between January 2008 and December 2009. Minimum inhibitory concentrations (MICs) were determined by agar dilution and Etest methods. Agar media of varying pH (pH 7.3, 6.0, or 5.0) were used to assess whether acidity influences the bactericidal effects of the agents tested. Time-kill assays were used to assess for synergism between different drug combinations.
  
  
  RESULTS
  A total of 176 non-duplicate H. pylori isolates from endoscopic specimens were tested. The following MIC90 (mg/L) (susceptible) results were obtained at neutral pH 7.3: amoxicillin, 0.25 (100%); tetracycline, 0.5 (100%); metronidazole, 32 (67.6%); clarithromycin, 0.25 (90.3%); ciprofloxacin, 1 (92.0%); gemifloxacin, 0.5 (94.9%); levofloxacin, 1 (93.2%); and moxifloxacin, 1 (91.5%). A decrease in pH from 6.0 to 5.0 significantly decreased the antimicrobial activity of levofloxacin and moxifloxacin against H. pylori. For clarithromycin-susceptible isolates, levofloxacin combined with clarithromycin provided both synergistic and bactericidal effects. For clarithromycin-resistant isolates with amoxicillin hypersusceptibility (MIC <0.01 mg/L), levofloxacin with amoxicillin or minocycline had at best additive effect but no bactericidal effects.
  
  
  CONCLUSIONS
  Amoxicillin, tetracycline, clarithromycin, and fluoroquinolones, but not metronidazole, showed good in vitro anti-H. pylori activity (>90% susceptible). Synergism was only observed for clarithromycin-susceptible isolates. Acidity adversely influenced the antimicrobial activity of levofloxacin against H. pylori.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan.
authors.forename: Aristine
authors.initials: A
authors.lastname: Cheng
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan. Electronic address: whsheng@ntu.edu.tw.
authors.forename: Wang-Huei
authors.initials: WH
authors.lastname: Sheng
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Jyh-Ming
authors.initials: JM
authors.lastname: Liou
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Hsiu-Po
authors.initials: HP
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Ming-Shiang
authors.initials: MS
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; Department of Internal Medicine, E-Da Hospital and I-Shou University, Kaohsiung, Taiwan.
authors.forename: Jaw-Town
authors.initials: JT
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Shan-Chwen
authors.initials: SC
authors.lastname: Chang
mesh_terms: D000362:Agar; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001706:Biopsy; D003470:Culture Media / Q000737:chemistry; D004357:Drug Synergism; D005753:Gastric Mucosa / Q000382:microbiology; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D013624:Taiwan
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D000362:Agar