title: Effect of cyclo-oxygenase inhibitors on Helicobacter pylori susceptibility to metronidazole and clarithromycin.
abstract: BACKGROUND
  We previously reported that aspirin inhibited Helicobacter pylori growth and suppressed the mutagenic effect of metronidazole.
  
  
  OBJECTIVE
  To determine the effects of a cyclo-oxygenase (COX)-2-specific inhibitor, SC-236, and a non-selective COX inhibitor, indometacin, on the growth, urease activity and antimicrobial susceptibility of H. pylori.
  
  
  METHODS
  Three H. pylori reference strains, and 18 clinical isolates were treated with SC-236 or indometacin for 24 and 48 h. Growth, urease activity and susceptibility to clarithromycin and metronidazole of the bacteria were assessed by viable colony counting, spectrophotometry and E-test respectively.
  
  
  RESULTS
  SC-236 and indometacin inhibited H. pylori growth in a dose-dependent manner with the lowest inhibitory concentrations of 0.03 and 0.1 mm, and the lethal concentrations of 0.09 and 0.3 mm, respectively. The numbers of CFU/mL in Brucella broth containing 0.09 mm SC-236 were 2 log lower at 24 h, and even 3 log lower at 48 h than that at 0 h (P = 0.035, compared with the vehicle control). Treatment of 0.3 mm indometacin reduced the number of CFU/mL by 1 log at 24 h compared with that at 0 h (P = 0.037 compared with the vehicle control). Helicobacter pylori urease activity began to decrease with 0.06 mm SC-236 at 24 h (P = 0.016), and 0.3 mm indometacin at 48 h (P = 0.025). MICs of metronidazole and clarithromycin against H. pylori were decreased significantly in the presence of 0.03 mm SC-236 or 0.1 mm indometacin (all P < 0.001).
  
  
  CONCLUSIONS
  Both SC-236 and indometacin suppressed the growth and urease activity of H. pylori in a dose-dependent manner, and increased its susceptibility to the antibiotics.
authors.affiliation: Department of Medicine, University of Hong Kong, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Gu
authors.forename: H H-X
authors.initials: HH
authors.lastname: Xia
authors.forename: W H
authors.initials: WH
authors.lastname: Wang
authors.forename: J D
authors.initials: JD
authors.lastname: Wang
authors.forename: W M
authors.initials: WM
authors.lastname: Wong
authors.forename: A O O
authors.initials: AO
authors.lastname: Chan
authors.forename: M F
authors.initials: MF
authors.lastname: Yuen
authors.forename: S K
authors.initials: SK
authors.lastname: Lam
authors.forename: H K-L
authors.initials: HK
authors.lastname: Cheung
authors.forename: X G
authors.initials: XG
authors.lastname: Liu
authors.forename: B C-Y
authors.initials: BC
authors.lastname: Wong
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D017291:Clarithromycin / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004347:Drug Interactions; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori; D006801:Humans; D008795:Metronidazole / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D000096926:Benzenesulfonamides
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D017291:Clarithromycin; D016861:Cyclooxygenase Inhibitors; D008795:Metronidazole; D011720:Pyrazoles; D013449:Sulfonamides; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides