In vitro synergistic activity between bismuth subcitrate and various antimicrobial agents against Campylobacter pyloridis (C. pylori)

Abstract

The in vitro interactions between bismuth subcitrate and a variety of antimicrobial agents against 12 Campylobacter pyloridis (C. pylorn) isolates were studied by the agar dilution checkerboard technique. The combination of bismuth subcitrate with the older quinolone, oxolinic acid, produced synergistic activity against all strains. This observation, however, could not be extended to the (aryl) fluoroquinolones, norfloxacin, ofloxacin, and difloxacin, since synergy was rare or absent when bismuth subcitrate was combined with these antibiotics. Among the other antimicrobial agents tested, rifampin and the beta-lactams frequently showed synergistic interactions with bismuth subcitrate. Nifuroxazide, a nitrofuran which is not significantly absorbed, showed MICs for C. pyloridis similar to those of bismuth subcitrate.Antimicrobial chemotherapy is helping to clarify the role of Campylobacter pyloridis (C. pylori) in the pathogenesis of gastritis. Histological studies have demonstrated that gastritis is cured after the organism is eradicated from the gastric mucosa (6, 9).A variety of antimicrobial agents display good activity against C. pyloridis in vitro (1,5,8). Yet when tested as single agents in clinical studies, they do not succeed in eradicating the organism. Failure of therapy and relapse are very common (10). The reason for this discrepancy between in vitro and clinical results has not been established. Possible explanations are poor penetration of the compounds in gastric mucus, destruction at acid pH, or both. The best results so far have been achieved with the combination of a nonabsorbed agent with topical activity, colloidal bismuth subcitrate, and a well-absorbed agent with systemic activity, amoxycillin (10). But clearly, therapy for C. pyloridisassociated infections still is suboptimal.The purpose of this study was to select, on the basis of synergistic activity in vitro, advantageous partner compounds for bismuth salts for combination therapy against C. pyloridis.The antibiotics (ampicillin, cefaclor, difloxacin, erythromycin, metronidazole, minocycline, nifuroxazide, nitrofurantoin, norfloxacin, ofloxacin, oxolinic acid, polymyxin B, rifampin, and tobramycin) were provided by the manufacturers. Bismuth subcitrate was obtained from Gist-Brocades nv, Delft, The Netherlands.The organisms which were tested were 12 recent C. pyloridis isolates obtained from antrum biopsies from patients at the University Hospital, Antwerp, Belgium. One isolate from each patient was tested. The identification of isolates was based on standard biochemical tests (7).Antibiotic solutions were prepared in appropriate buffer solutions, distilled water, or both. Bismuth subcitrate powder was brought into colloidal suspension in 1 N NaOH and further diluted in distilled water.Antibacterial activity was determined by the agar dilution technique, with Mueller-Hinton agar (GIBCO Diagnostics, Madison, Wis.) supplemented with 10% sterile defibrinated * Corresponding author. horse blood to support growth of the organism. The inoculu...

Lansoprazole, a novel benzimidazole proton pump inhibitor, and its related compounds have selective activity against Helicobacter pylori

“…All of the plates for the MIC tests were further incubated for 2 additional days, but there were no changes in the MICs. Bismuth citrate was active against all of the strains tested, and these MICs agree well with those previously reported by several investigators (8,22,36). Cimetidine, ranitidine, and famotidine were almost inactive, and these results are also in agreement with those reported elsewhere (8,32).…”

“…In this study, we found that two antiulcer agents with the ability to inhibit the proton pump mechanisms in gastric parietal cells, lansoprazole and omeprazole, showed marked in vitro activities against H. pylori. In particular, lansoprazole, recently developed (27,31), was fourfold more active than omeprazole, and the in vitro activity of the former agent was comparable to that of bismuth salts, which are used as an antiulcer agent and are known to have antibacterial activity against this organism (1,8,22,36). Mainguet et al (14) and Biasco et al (2) have reported that omeprazole treatment of patients with duodenal ulcer and positive cultures for H. pylori resulted in negative cultures immediately after the treatment, but these investigators have not determined whether the efficacy of the drug is attributable to a direct action on the bacteria or to modifications of the intragastric content.…”

“…In vitro, a number of antibiotics, including P-lactams, macrolides, and quinolones, have been known to be highly active against H. pylori (1,8,10,13,22,30,32,33,36). However, when tested as single agents in clinical studies, erythromycin (23), doxycycline (35), ofloxacin (5), ciprofloxacin (34), and norfloxacin (24) have not succeeded in eradicating H. pylori.…”

“…Taking a close association between H. pylori and gastroduodenal disorders into consideration, we examined the activities against this organism of various types of antiulcer agents, including lansoprazole (AG-1749), a novel benzimidazole proton pump inhibitor (27,31), by an agar dilution method. In this report, we show that the benzimidazole proton pump inhibitors have a notable and selective activity against H. pylori and that the activities of lansoprazole and its related compounds are comparable or superior to that of a bismuth salt known to posess a reliable activity against this organism (1,8,22,36). The effect of lansoprazole on the growth kinetics and morphology of H. pylori growing in a liquid medium was also investigated.…”

The Action of Bismuth against Helicobacter pylori Mimics but Is Not Caused by Intracellular Iron Deprivation

“…The oldest regimen, an extremely effective one for clearing H. pylori infection, uses bismuth in combination with certain antibiotics (2,51). Bismuth "triple therapy" consists of a bismuth compound (usually CBS or bismuth subsalicylate) in combination with metronidazole and tetracycline or amoxicillin (16) and reportedly cures 87.9% of patients within 1 week of treatment and 89.2% of patients within 2 weeks of treatment (49).…”