Proposed mechanism for metronidazole resistance in Helicobacter pylori.

Metronidazole MIC values were determined for ten isolates of Helicobacter pylori. Under microaerobic conditions four were inhibited by less than 0.25 mg/L, two strains required 2.0 mg/L and four strains had MIC greater than 32 mg/L. The strains were tested for their susceptibility to metronidazole after varying lengths of anaerobic exposure prior to or during microaerobic incubation. The susceptibility was determined by E-test and traditional agar dilution technique. The level of susceptibility of primarily susceptible strains was not significantly affected by a 2 to 24 h period of anaerobic incubation. However, the effect on resistant strains was dramatic. These strains were increasingly susceptible when a 2 to 12 h period of anaerobicity was provided anytime during the first 48 h and fully susceptible (MIC less than 0.1 mg/L) if 24 h of anaerobicity was provided. When tested again under microaerobic conditions the strains exhibited their original MIC values. The composition of the medium did not influence the results. We propose that "metronidazole resistance" in H. pylori is due to a decreased ability of these strains to achieve a sufficiently low redox potential under microaerobic conditions for the necessary reduction of metronidazole, and that these strains during short periods of anaerobicity manage to reduce and "store" sufficient amounts of metronidazole to appear fully susceptible after subsequent microaerobic incubation. microaerobic incubation.