Effect of cyclo-oxygenase inhibitors on Helicobacter pylori susceptibility to metronidazole and clarithromycin.
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.
Gu
Q
Q
Department of Medicine, University of Hong Kong, China.
Xia
H H-X
HH
Wang
W H
WH
Wang
J D
JD
Wong
W M
WM
Chan
A O O
AO
Yuen
M F
MF
Lam
S K
SK
Cheung
H K-L
HK
Liu
X G
XG
Wong
B C-Y
BC
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
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