Effect of clarithromycin and omeprazole therapy on the diversity and stability of genotypes of Helicobacter pylori from duodenal ulcer patients.
The genotypes of multiple isolates of Helicobacter pylori from 17 duodenal ulcer patients in the United Kingdom were compared to determine reasons for treatment failure. Isolates were from antrum and corpus biopsies taken before and after dual therapy with clarithromycin and omeprazole. All isolates were tested for antibiotic resistance and characterised by a novel scheme combining polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the ureA + ureB and 23S rRNA genes, vacA signal and midregion genotypes, and PCR detection of cagA. Combined genotypes of paired pre- and post-treatment isolates from 8 patients showed an infection with a single strain of H. pylori that had acquired resistance to clarithromycin. In 4 other patients, acquisition of clarithromycin resistance was associated with the presence of different strain types of H. pylori. The remaining 5 patients had clarithromycin-sensitive isolates. Overall, H. pylori from different patients had diverse genotypes, yet most (70%) were colonized by the same predominant and stable strain in both the antrum and corpus. There was no link between the emergence of in vitro clarithromycin resistance and a particular strain genotype for these UK isolates. It was concluded that colonization with a clarithromycin-resistant H. pylori was due to selection of a resistant strain or clonal variant within the infecting population. Present genomic markers had low predictive value for emergence of resistance.
Owen
R J
RJ
Helicobacter Reference Unit, Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK.
Slater
E R
ER
Gibson
J
J
Lorenz
E
E
Tompkins
D S
DS
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001483:Base Sequence; D017291:Clarithromycin / Q000008:administration & dosage / Q000627:therapeutic use*; D017931:DNA Primers; D004359:Drug Therapy, Combination; D004381:Duodenal Ulcer / Q000188:drug therapy / Q000382:microbiology*; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D009853:Omeprazole / Q000008:administration & dosage / Q000627:therapeutic use*; D017354:Point Mutation; D012338:RNA, Ribosomal, 23S / Q000235:genetics
D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D017931:DNA Primers; D012338:RNA, Ribosomal, 23S; D017291:Clarithromycin; D009853:Omeprazole