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...