The in vitro antimicrobial activity of ciprofloxacin (Bay o 9867) was compared with those of the other new fluorated piperazinyl-substituted quinoline derivatives: norfloxacin, ofloxacin, and pefloxacin, as well as with those of the earlier analogs, nalidixic acid and oxolinic acid. Virtually no resistance against the new fluorated piperazinyl-substituted quinoline derivatives was observed. As a rule, ciprofloxacin was about four times more active in vitro than the other new fluorated piperazinyl-substituted quinoline derivatives. [4]). These products are structurally related to the other naphthyridine and quinoline derivatives, such as nalidixic acid and oxolinic acid ( Fig. 1), but show an expanded antibacterial spectrum. Furthermore, no cross resistance has been described between the earlier analogs and the fluorated piperazinyl-substituted quinoline derivatives.The purpose of this study was to compare all the fluorated piperazinyl-substituted quinoline derivatives.The antibiotics were provided by their respective manufacturers. A total of 343 bacterial isolates included specimens recently isolated from patients hospitalized at the Akademisch Ziekenhuis Antwerpen, Antwerp, Belgium, as well as isolates which had been stored frozen because of some unique feature, such as pattern of resistance, pathogenicity, and rarity of occurrence.Antibiotic solutions were prepared in appropriate buffer solutions or distilled water or both.Antibacterial activity was determined by the agar dilution technique with Mueller-Hinton medium (Difco Laboratories; GIBCO Diagnostics) supplemented with 10% whole human blood to support the growth of streptococci and with 5% lysed human blood and vitamin K for anaerobic bacteria.The inoculum was a 1-,ul suspension of 104 viable cells obtained by dilution in peptone water from an overnight nutrient broth culture yielding about 109 CFU/ml and was applied with a semiautomatic replicator. For Streptococcus spp. and Bacteroides spp., Todd-Hewitt broth and thioglycolate broth, respectively, were used. Streptococcus pneu-* Corresponding author. 518 moniae was also grown in Todd-Hewitt broth, yielding a viable count of 108 CFU/ml.The MIC was the lowest concentration that inhibited visible growth of organisms on agar after 18 h at 35°C (48 h at 35°C in an anaerobic chamber for anaerobic bacteria).Virtually no resistance against ciprofloxacin was noted among the 343 strains tested, with MICs required to inhibit the majority of isolates ranging between 0.008 ,ug/ml or less and 0.5 ,ug/ml. The few exceptions, requiring for inhibition MICs above 0.5 ,ug/ml, were Providencia sp.(1 strain of 6 tested), Flavobacterium sp. (3 strains of 3 tested), Achromobacter sp. (2 strains of 2 tested), Acinetobacter sp.(1 strain of 8 tested), Pseudomonas maltophilia (3 strains of 4 tested), Streptococcus group D (9 strains of 21 tested), and Bacteroides fragilis (13 strains of 13 tested).The activities of ciprofloxacin and the other fluorated piperazinyl-substituted quinoline derivatives, norfloxacin, ofloxacin and pe...

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...

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