Treatment Failure of Ofloxacin in Campylobacter Pylori Infection

The antibacterial activity of TAK-083 was tested against 54 clinical isolates of Helicobacter pylori and was compared with those of amoxicillin, clarithromycin, and metronidazole. The growth-inhibitory activity of TAK-083 was more potent than that of amoxicillin, clarithromycin, or metronidazole (the MICs at which 90% of the strains are inhibited were 0.031, 0.125, 64, and 8 g/ml, respectively). The antibacterial activity of TAK-083 was highly selective against H. pylori; there was a >30-fold difference between the concentration of TAK-083 required to inhibit the growth of H. pylori and that required to inhibit the growth of common aerobic and anaerobic bacteria. Exposure of H. pylori strains to TAK-083 at the MIC or at a greater concentration resulted in an extensive loss of viability. When four H. pylori strains were successively subcultured in the medium containing subinhibitory concentrations of TAK-083, no significant change in the MICs of this compound was observed. TAK-083 strongly inhibited the formation of tryptophanyl-tRNA in H. pylori while exhibiting little effect on the same system in eukaryotes. TAK-083 was efficacious in the treatment of gastric infection caused by H. pylori in Mongolian gerbils. The results presented here indicate that TAK-083 is a promising candidate for the treatment of H. pylori infection.

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confidence: 99%

In Vitro and In Vivo Antibacterial Activities of TAK-083, an Agent for Treatment of Helicobacter pylori Infection

Kanamaru

Nakano

Toyoda

et al. 2001

“…Histological studies have demonstrated that gastritis can be cured after this organism is eradicated from the gastric mucosa (24,27). However, clinical therapy by a single antibiotic has not been successful (12,27,28,40,42). Instead, combinations of chemotherapeutic agents including bismuth salts have yielded better results (27,43).…”

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confidence: 99%

Potent inhibitory action of the gastric proton pump inhibitor lansoprazole against urease activity of Helicobacter pylori: unique action selective for H. pylori cells

Nagata

Satoh

Iwahi

et al. 1993

146

The gastric proton pump inhibitor lansoprazole, its active analog AG-2000, and omeprazole dose dependently inhibited urease activity extracted with distilled water from Helicobacterpylori cells; the 50%1 inhibitory concentrations were between 3.6 and 9.5 ,M, which were more potent than those of urease inhibitors, such as acetohydroxamic acid, hydroxyurea, and thiourea. These compounds also inhibited urease activity in intact cells of H. pylori and Helicobacter mustelae but did not inhibit ureases from other bacteria, such as Proteus vulgaris, Proteus mirabilis, and Providencia rettgeri. The mechanism of urease inhibition was considered to be blockage of the SH groups of H. pylori urease, since SH residues in the enzyme decreased after preincubation with lansoprazole and glutathione or dithiothreitol completely abolished the inhibitory action. The SH-blocking reagents A -ethylmaleinide and idoacetamide were also examined for their inhibition of the urease activity; their 5W0 inhibitory tontentrations were 100-to 1,000-fold higher than those of lansoprazole. These results suggest that lansoprazole and omeprazole can potently and selectively inhibit H. pylori urease and that inhibition may be related to earlier findings indicating that these compounds have selective activity against HP growth.

“…However, two recent reports have dampened enthusiasm for the role of these agents in the treatment of C. pylori-associated gastritis. Glupczynski et al (4) described five patients who were treated with ofloxacin and ranitidine, in whom resistance to ofloxacin developed during treatment; cross-resistance to other fluoroquinolones was also observed. Stone and co-workers (16) have reported a failure to eradicate C. pylori in 9 of 14 patients with …”

Section: 13 15 17)mentioning

confidence: 99%

Comparative in vitro activities of six new fluoroquinolones and other oral antimicrobial agents against Campylobacter pylori

Simor

Ferro

Low

1989

The in vitro susceptibilities of 56 clinical isolates of Campylobacter pylori to six new fluoroquinolones and other oral antimicrobial agents were determined by an agar dilution technique. Ciprofloxacin was the most active of the fluoroquinolones (MIC for 90% of strains tested [MIC90], 0.05 microgram/ml). Other fluoroquinolones had variable activities, although most isolates were moderately susceptible to fleroxacin (MIC90, 4 micrograms/ml) and lomefloxacin (MIC90, 4 micrograms/ml).