In vitro anti-Helicobacter pylori activity of BAS-118, a new benzamide derivative.
The antibacterial activity of BAS-118, a new benzamide derivative, against Helicobacter pylori and other species of bacteria was investigated, as was the in vitro ability of the compound to induce drug resistance in H. pylori. The MICs of BAS-118 for 155 isolates of H. pylori, including 30 clarithromycin (CAM)-resistant isolates (MIC > or= 1.56 mg/L) and 25 metronidazole (MNDZ)-resistant isolates (MIC >or = 6.25 mg/L), and 29 reference strains of other genera were determined by an agar dilution method. The MIC(50), MIC(90) and MIC range of BAS-118 for 100 randomly selected isolates of H. pylori were <or =0.003, 0.013 and < or =0.003-0.025 mg/L, respectively, with similar values obtained for CAM- and MNDZ-resistant isolates. Furthermore, MICs of BAS-118 for five H. pylori strains increased no more than two-fold after 10 serial passages in the presence of subinhibitory concentrations. BAS-118 exhibited a low antibacterial activity against the 29 non-H. pylori strains, with MICs of >or =8 mg/L. In summary, BAS-118 is a novel anti-H. pylori agent with a potent and selective antibacterial activity, which includes CAM- and MNDZ-resistant isolates. Furthermore, BAS-118 does not appear to induce drug resistance readily in vitro.
Kobayashi
Intetsu
I
Chemotherapy Division, Mitsubishi Kagaku Bio-Clinical Laboratories, 3-30-1 Shimura, Itabashi-ku, Tokyo 174-8555, Japan. mbc-ka@sa2.so-net.ne.jp
Muraoka
Hiroe
H
Hasegawa
Miyuki
M
Saika
Takeshi
T
Nishida
Minoru
M
Kawamura
Makoto
M
Ando
Ryoichi
R
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D017291:Clarithromycin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D016481:Helicobacter Infections / Q000150:complications / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008795:Metronidazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010437:Peptic Ulcer / Q000209:etiology / Q000382:microbiology
D000900:Anti-Bacterial Agents; D001549:Benzamides; C471412:N-methyl-3-(2-(2-naphthyl)acetylamino)benzamide; D008795:Metronidazole; D017291:Clarithromycin