Treatment failure of norfloxacin against Campylobacter pylori and chronic gastritis in patients with nonulcerative dyspepsia

269

156

The activities of various types of antiulcer agents against Helicobacter pylori (formerly called Campylobacter pylon) strains were determined by an agar dilution method. Among the compounds tested, two benzimidazole proton pump inhibitors, lansoprazole (AG-1749) and omeprazole, were found to have significant activities against this organism. The activity of lansoprazole was comparable to that of bismuth citrate, with MICs ranging from 3.13 to 12.5 ,ug/ml, and fourfold more potent than that of omeprazole. A major metabolite and two acid-converted rearrangement products of lansoprazole also exhibited good activities comparable or superior to that of the parent compound. Exposure to lansoprazole of H. pylori growing in a liquid medium led to an extensive loss of viability without a reduction in culture turbidity and produced an aberrant bacterial morphology characterized by the irregular constriction of cells and the collapse of cell surface structures. The antibacterial activity of lansoprazole and its related compounds was selective against H. pylori; common aerobic and anaerobic bacteria and Campylobacterjejuni were not inhibited by 100 ,ug/ml.

Section: Resultsmentioning

confidence: 99%

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

Iwahi

Satoh

Nakao

et al. 1991

269

156

“…Strains resistant to ciprofloxacin, metronidazole, erythromycin, and tobramycin were isolated. The experiments failed to select organisms resistant to bismuth subsalicylate, furazolidone, or amoxicillin, although the MIC of amoxicillin was increased 4-to 16-fold. With the exception of erythromycin, organisms with the selected resistance were stable after at least three passages on antibacterial agent-free medium.…”

mentioning

confidence: 99%

“…The second major problem has been the emergence of resistant strains during singleagent treatment. The development of resistance has been reported during treatment with several quinolones (10,16 (6,10), and rifampin (10).…”

mentioning

confidence: 99%

In vitro selection of resistant Helicobacter pylori

Haas

Nix

Schentag

1990

123

Four strains of Heikobacter pylori were subjected to an in vitro serial passage technique to compare the propensity of the organisms to develop resistance to seven classes of antibacterial agents. The passages were made on serially doubling concentrations of antibacterial agents incorporated into agar starting at one-half the base-line MIC. The frequency of spontaneous resistance was also determined for each strain at four and eight times the MIC of each antibacterial agent. Strains resistant to ciprofloxacin, metronidazole, erythromycin, and tobramycin were isolated. The experiments failed to select organisms resistant to bismuth subsalicylate, furazolidone, or amoxicillin, although the MIC of amoxicillin was increased 4-to 16-fold. With the exception of erythromycin, organisms with the selected resistance were stable after at least three passages on antibacterial agent-free medium. Spontaneous resistance rates were generally of a low magnitude and were not predictive of the serial passage results.Helicobacter pylori (formerly Campylobacter pylori) is accepted as the most common and most important cause of chronic active gastritis and represents one of the common chronic infections of humans. H. pylori infection and gastritis are also associated with the vast majority of cases of chronic, recurrent duodenal ulcer, with a growing body of data supporting an important etiologic role for the organism in that disease (4, 7).Antibacterial therapy resulting in the clearance of H. pylori from the gastric mucosa has led to histologic improvement or normalization of chronic active gastritis (5,17,19). In patients with duodenal ulcers associated with H. pylori infections, effective eradication of the organism has resulted in improved healing of ulcers (12) and significantly lower rates of ulcer relapse (3, 12). These findings support a role for antibacterial therapy in the treatment of H. pyloriassociated upper gastrointestinal diseases.Two major problems have been encountered in the treatment of H. pylori infections, despite its in vitro susceptibility to a wide array of antibacterial agents. First, relapse of H. pylori is common following what appears to be successful treatment (5,17,19). Relapse is presumably due to incomplete eradication of the organism. The second major problem has been the emergence of resistant strains during singleagent treatment. The development of resistance has been reported during treatment with several quinolones (10, 16; Y. Glupczynski, M. Labbe, A. Burette, M. Delmee, V. Avesani, and C. Bruck, Letter, Lancet i:1096, 1987; J. W. Stone, R. Wise, I. A. Donovan, and J. Gearty, Letter, J. Antimicrob. Chemother. 22:92-93, 1988), nitroimidazoles (6, 10), and rifampin (10).The purpose of this in vitro study was to compare the propensity of H. pylori strains to develop resistance to several antibacterial agents by using a serial passage technique (22) and to investigate the rates of spontaneous resistance to the study drugs.

“…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).…”

mentioning

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

147

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.