Abstract
The doubling times of bacteria at sites of colonization or infection are considerably longer than those in laboratory culture media, and slow growth reduces the susceptibility of bacteria to antimicrobial agents. Helicobacter pylori is susceptible to a wide range of antimicrobial agents in vitro; however, tests for inhibitory activity do not adequately predict which antimicrobial agents will eradicate slowly growing H. pylori from the stomachs of patients. The chemostat can be used to compare the bactericidal activities of antimicrobial substances against slowly growing bacteria. In this study we compared the bactericidal activities of antimicrobial agents against slowly growing H. pylori. The bactericidal activities of erythromycin, minocycline, ampicillin, amoxicillin, cefixime, metronidazole, and bismuth subcitrate against slowly growing H. pylori NCTC 11,637 in a chemostat were compared. Antimicrobial agents were added to the system at four to eight times the MIC. Exposure of H. pylori to metronidazole was associated with the rapid development of metronidazole resistance, preventing assessment of the bactericidal activity of metronidazole. Resistance to the other antimicrobial agents tested did not develop. The poor bactericidal activities of the antimicrobial agents against slowly growing H. pylori may be a contributory factor in limiting their clinical efficacies. Of the agents tested, only amoxicillin and bismuth subcitrate showed bactericidal activity against slowly growing H. pylori. The chemostat allows comparison of the bactericidal activities of antimicrobial agents against slowly growing H. pylori and may therefore provide results which more accurately identify those agents or combinations of agents that will eradicate H. pylori from patients.