Inhibitory action of a novel proton pump inhibitor, rabeprazole, and its thioether derivative against the growth and motility of clarithromycin-resistant Helicobacter pylori.
BACKGROUND
Clarithromycin-resistant Helicobacter pylori (CRHP) has increasingly been isolated from patients in Japan. The aim of our study was to test whether proton pump inhibitors (PPIs) and their thioether derivatives, which are secreted into the gastric mucosa, could inhibit the growth and motility (a factor in colonization) of CRHP.


METHODS
CRHP was isolated from patients who had experienced gastritis or peptic ulcers in Tokyo and Niigata. Drugs and related agents tested were omeprazole, lansoprazole, rabeprazole, the thioether derivative of rabeprazole (rabeprazole-TH), clarithromycin, amoxicillin and metronidazole. The MICs of the drugs and agents for H. pylori strains were determined by the agar dilution


METHODS
Bacterial swimming in a liquid layer was examined under an inverted, phase-contrast microscope.


RESULTS
The PPIs and rabeprazole-TH, but not the anti-H. pylori agents, inhibited the motility of CRHP at both pH 7.4 and 6.0. The concentrations (microg/ml) necessary to inhibit 50% of the motility at pH 7.4 were 0.25-0.5, 8-32, 8-16 and 128-256 for rabeprazole-TH, rabeprazole, lansoprazole and omeprazole, respectively. Rabeprazole-TH exhibited the strongest inhibitory effect against the growth of CRPH (MIC, 0.5 microg/ml).


CONCLUSIONS
Rabeprazole-TH, which is secreted into the gastric mucosa, had the strongest inhibitory action against both the growth and motility of CRHP, suggesting that it is a potential novel agent for CRHP eradication.
Ohara
T
T
Department of Bacteriology, School of Medicine, Niigata University, Niigata, Japan.
Goshi
S
S
Taneike
I
I
Tamura
Y
Y
Zhang
H M
HM
Yamamoto
T
T
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D017291:Clarithromycin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D005756:Gastritis / Q000382:microbiology*; D016481:Helicobacter Infections / Q000188:drug therapy; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D007564:Japan; D009068:Movement / Q000187:drug effects; D009853:Omeprazole / Q000031:analogs & derivatives; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D013440:Sulfides / Q000737:chemistry / Q000494:pharmacology*; D017211:Treatment Failure
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D054328:Proton Pump Inhibitors; D013440:Sulfides; D064750:Rabeprazole; D017291:Clarithromycin; D009853:Omeprazole