Direct detection of Helicobacter pylori resistance to macrolides by a polymerase chain reaction/DNA enzyme immunoassay in gastric biopsy specimens

Gut. 1999 Apr;44(4):463-7. doi: 10.1136/gut.44.4.463.

Abstract

Background: The increasing use of macrolides especially in the treatment of Helicobacter pylori infection has led to an increase in resistant strains. The resistance of H pylori to macrolides, especially clarithromycin, is one of the major causes of eradication failure. In H pylori, clarithromycin resistance is due to point mutations localised in domain V of 23S rRNA.

Aim: To develop a molecular technique based on amplification of a relevant fragment of the 23S rRNA and colorimetric hybridisation in liquid phase to detect directly in biopsy specimens the type of mutation associated with resistance of H pylori to clarithromycin.

Methods: Gastric biopsy samples from 61 patients were submitted to this test. The results were compared with standard methods (determination of minimal inhibition concentration, polymerase chain reaction/restriction fragment length polymorphism, and/or DNA sequencing) in order to evaluate the test and to define the cut off values, specificity, and sensitivity.

Results: The 14 biopsy samples in which H pylori was not detected did not give a positive result in any assay, and the 14 samples harbouring strains susceptible to clarithromycin gave a positive result with the wild type probe as expected. The 33 biopsy specimens containing resistant strains always gave a positive signal with one of the probes detecting resistant organisms, but in eight cases they also reacted with the wild type probe, indicating that a mixture of resistant and susceptible organisms was present.

Conclusion: The importance of this new assay is that it allows the detection of multiple genotypes corresponding to either heterogeneous genotypes or mixed infections. Moreover, it allows in a single step not only the detection of H pylori but also the determination of its susceptibility to clarithromycin directly in biopsy specimens without the need for culture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Biopsy
  • Clarithromycin / pharmacology
  • DNA, Bacterial / genetics*
  • DNA, Ribosomal / genetics*
  • Genotype
  • Helicobacter pylori / drug effects*
  • Helicobacter pylori / genetics
  • Humans
  • Immunoenzyme Techniques
  • Microbial Sensitivity Tests / methods*
  • Polymerase Chain Reaction / methods
  • Polymorphism, Restriction Fragment Length
  • RNA, Ribosomal / genetics

Substances

  • Anti-Bacterial Agents
  • DNA, Bacterial
  • DNA, Ribosomal
  • RNA, Ribosomal
  • RNA, ribosomal, 26S
  • Clarithromycin