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. Aim: 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). Conclusion: 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.