title: Gemifloxacin can partially overcome quinolone resistance of H. pylori with gyrA mutation in Taiwan.
abstract: BACKGROUND
  The levofloxacin resistance caused by gyrA gene mutation is rising rapidly to limit wide application for Helicobacter pylori eradication. We investigated whether gemifloxacin has a superior antimicrobial activity to levofloxacin against H. pylori.
  
  
  METHODS
  Forty-four consecutive clinical H. pylori isolates with levofloxacin resistance and 80 randomly selected levofloxacin-sensitive controls were tested for gemifloxacin sensitivity by E-test. The resistance to levofloxacin or gemifloxacin was defined as minimal inhibitory concentration (MIC) > 1 mg/L. The clinical features and GyrA mutation patterns checked by direct sequencing were also analyzed to assess its association with the H. pylori gemifloxacin resistance.
  
  
  RESULTS
  All levofloxacin-sensitive H. pylori isolates were sensitive to gemifloxacin. Eight strains (18.2%) resistant to levofloxacin could be still sensitive to gemifloxacin. Gemifloxacin achieved a 5-time lower in MIC levels against levofloxacin-resistant isolates. Nearly all levofloxacin-resistant isolates (97.7%, 43/44) had GyrA mutation at amino acid position 87 or 91. Double mutation sites may play dual roles in quinolone resistance, as N87K plus H57Y or D91N plus V77A mutations showed high-level resistance to both quinolones; whereas D91Y plus A97V or D91N plus A97V mutations showed low level levofloxacin resistance to become sensitive to gemifloxacin. In H. pylori isolates with single N87K, D91Y or D91N mutation, near 20% was gemifloxacin-sensitive and levofloxacin-resistant. The gemifloxacin-resistant rate of H. pylori was higher in patients with gastric ulcer than in those without (p <.05).
  
  
  CONCLUSIONS
  Gemifloxacin is superior to levofloxacin in antimicrobial activity against clinical H. pylori isolates, and even overcome some levofloxacin resistance.
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Chang
authors.forename: Cheng-Yen
authors.initials: CY
authors.lastname: Kao
authors.forename: Chung-Tai
authors.initials: CT
authors.lastname: Wu
authors.forename: Ay-Huey
authors.initials: AH
authors.lastname: Huang
authors.forename: Jiunn-Jong
authors.initials: JJ
authors.lastname: Wu
authors.forename: Hsiao-Bai
authors.initials: HB
authors.lastname: Yang
authors.forename: Hsiu-Chi
authors.initials: HC
authors.lastname: Cheng
authors.forename: Bor-Shyang
authors.initials: BS
authors.lastname: Sheu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D027081:DNA Gyrase / Q000235:genetics* / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D000077735:Gemifloxacin; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology*; D016480:Helicobacter pylori / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009287:Naphthyridines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D013624:Taiwan
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D009287:Naphthyridines; D015363:Quinolones; D027081:DNA Gyrase; D000077735:Gemifloxacin