The role of ranitidine bismuth citrate in significantly reducing the emergence of Helicobacter pylori strains resistant to antibiotics.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
RBC significantly decreased resistance acquisition in an inherently sensitive strain and also decreased resistance emergence in a strain that readily became metronidazole-resistant.
McLaren
A
A
GlaxoWellcome Medicines Research Centre, Stevenage, Hertfordshire, United Kingdom.
Donnelly
C
C
McDowell
S
S
Williamson
R
R
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001729:Bismuth / Q000494:pharmacology*; D017291:Clarithromycin / Q000494:pharmacology; D004347:Drug Interactions; D004352:Drug Resistance, Microbial; D016480:Helicobacter pylori / Q000187:drug effects*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008795:Metronidazole / Q000494:pharmacology; D011899:Ranitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013307:Streptomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D006635:Histamine H2 Antagonists; D008795:Metronidazole; C073340:ranitidine bismuth citrate; D011899:Ranitidine; D017291:Clarithromycin; D001729:Bismuth; D013307:Streptomycin