The Role of Ranitidine Bismuth Citrate in Significantly Reducing the Emergence of Helicobacter pylori Strains Resistant to Antibiotics

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Abstract
This study was carried out to investigate the clinical observation that the emergence of antibiotic resistance can be reduced in Helicobacter pylori if agents are administered in combination with bismuth salts. Two H. pylori clinical isolates were grown on chocolate Columbia agar containing either ranitidine bismuth citrate (RBC) at one-half lethal concentration (8 micrograms/ml) or no drug control for 22 subcultures. After 1, 5, 8, 14, 17, and 22 subcultures, the emergence of antibiotic resistance to metronidazole, clarithromycin, and streptomycin was calculated and statistically analyzed. Acquisition of resistance to metronidazole was reduced significantly for both strains (p = .007 and 0.014) and for one strain against clarithromycin (p = .037). However, spontaneous emergence of resistance to streptomycin was not altered significantly. In an analysis of the effect of long-term exposure of the isolates to RBC, susceptibility to bismuth was unaltered in one strain and had risen by only twofold in the other at experiment termination. RBC significantly decreased resistance acquisition in an inherently sensitive strain and also decreased resistance emergence in a strain that readily became metronidazole-resistant.