In vitro antagonism of rabeprazole and metronidazole upon clinical isolates of Helicobacter pylori.

BACKGROUND: Rabeprazole inhibits Helicobacter pylori in vitro. This property could influence the antibacterial activity of metronidazole or amoxicillin. Our goal was to evaluate in vitro the effect of rabeprazole upon the antibacterial activity of metronidazole and amoxicillin. METHODS: The minimal inhibitory concentration (MIC) was determined by agar dilution upon 30 clinical isolates, and the antibacterial effect of the combined drugs was estimated by calculating the fractional inhibitory concentration index (FICI). RESULTS: Nine strains (30%) were resistant to metronidazole (MIC 8-256 mg/l) while only 1 strain was resistant to amoxicillin (MIC 1.0 mg/l). Rabeprazole also inhibited H. pylori (MIC 0.125-1.0 mg/l). The association of metronidazole and rabeprazole showed synergism in 30% of the strains (FICI < or =0.25), but also antagonism in 23.3% of the clinical isolates (FICI > or =4.0). Mostly, amoxicillin-rabeprazole showed an effect of synergism (53.3%). CONCLUSION: The results presented suggest the need to keep in mind that failure in eradication therapies based on metronidazole and rabeprazole could be due to an antagonism of the drugs.