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Anaerobic Preincubation and the Susceptibility of H. pylori: Understanding the Mechanism of Metronidazole Resistance.

VAN DER WOUDEN EJ, VAN ZWET AA, THIJS JC, DE JONG A, GERRITS MM, KUSTERS JG; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 220 (abstract no. 910).

Bethesda Hosp., Dept. of Internal Med., Hoogeveen, NETHERLANDS

Anaerobic preincubation in the presence of metronidazole (MET) turns MET resistant strains of Helicobacter pylori (H. pylori) into susceptible ones. No data exist on the minimal period of preincubation needed for this transformation. Furthermore, it is unknown whether de novo protein synthesis is necessary for this transformation.METHODS: Nine MET resistant strains ( MIC : 8 mg/ml) were tested. Blood agarplates were inoculated with multiple H. pylori colonies and an E-test strip was applied. In the presence of this strip the plates were preincubated under anaerobic conditions for 0, 15, 30, 60, 120, 240 and 480 minutes, respectively. After each preincubation, the plates were stored under micro-aerophilic conditions and read after 3 days. Thereafter, the test was repeated in broth both in the presence and absence of the protein synthesis inhibitor chloramphenicol.RESULTS: Without anaerobic preincubation the median MIC was 192 mg/ml (range 24 to >256 mg/ml). With increasing preincubation-time the MIC decreased slowly for all strains tested. After 120 minutes of preincubation all strains were still resistant. After 480 minutes, however, all strains were susceptible (median MIC 1,3 mg/ml, range 0,38-4 mg/ml). Chloramphenicol did not prevent the loss of resistance under anaerobic preincubation.CONCLUSION: Only extended periods of anaerobic preincubation induces MET susceptibility in resistant H. pylori strains. Our chloramphenicol experiments indicate that de novo protein synthesis is not necessary to induce this phenomenon. It has been shown that null-mutations in an oxygen insensitive nitroreductase induces resistance, but our data indicate that there is also an alternative way to reduce MET. However, this results in an unstable product that is deactivated by 'futile cycling' in the presence of oxygen.

Publication Types:
  • Meeting Abstracts
Keywords:
  • Chloramphenicol
  • Helicobacter pylori
  • Metronidazole
  • Microbial Sensitivity Tests
  • Nitroreductases
Other ID:
  • GWAIDS0007634
UI: 102245130

From Meeting Abstracts




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