title: Study of the combination of ranitidine bismuth citrate and metronidazole against metronidazole-resistant Helicobacter pylori clinical isolates.
abstract: The in-vitro activity of a combination of ranitidine bismuth citrate (RBC) and metronidazole against metronidazole-resistant Helicobacter pylori strains (MIC > or = 8 mg/L) was evaluated by agar dilution chequerboard and killing curve methods. Twenty-five metronidazole-resistant strains were used in the chequerboard method, using Mueller-Hinton agar plus 7% lysed horse blood, an inoculum of 10(6) cfu/spot and incubation in a 10% CO2 atmosphere at 37 degrees C for 3-5 days. Synergy was defined as a fractional inhibitory concentration (FIC) index of < or = 0.5, partial synergy as 0.5 < FIC < or = 1, indifference as 1 < FIC < or = 4 and antagonism as FIC > 4. For nine strains, killing curves were constructed for metronidazole and RBC individually and in combination at 1 x MIC. The number of viable colonies was counted at time 0 and after 2, 4, 6, 8 and 24 h; the combination was defined as synergic if it produced a decrease of > or = 2 log10 cfu/mL compared with the most active single agent. Metronidazole MICs ranged from 8 to 128 mg/L and RBC MICs from 0.125 to 4 mg/L. The minimum FIC ranged from 0.28 to 1 and the maximum FIC from 1 to 1.25. When RBC and metronidazole were combined, all the metronidazole-resistant H. pylori strains revealed partial (68%) or total (32%) synergy. Five out of the nine strains also exhibited synergy at 4, 6 or 8 h incubation when tested by the killing curve method although three other strains exhibited no synergy. In the last strain, a 2log10 decrease in the initial number was observed with RBC alone or combined with metronidazole.
authors.affiliation: Department of Microbiology, Hospital Universitario de la Princesa, Madrid, Spain. mlbrea@microb.net
authors.forename: M
authors.initials: M
authors.lastname: López-Brea
authors.forename: D
authors.initials: D
authors.lastname: Domingo
authors.forename: I
authors.initials: I
authors.lastname: Sánchez
authors.forename: N
authors.initials: N
authors.lastname: Prieto
authors.forename: T
authors.initials: T
authors.lastname: Alarcón
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001729:Bismuth / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D016480:Helicobacter pylori / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008795:Metronidazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D011899:Ranitidine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D008795:Metronidazole; C073340:ranitidine bismuth citrate; D011899:Ranitidine; D001729:Bismuth