Published online Mar 7, 2018. doi: 10.3748/wjg.v24.i9.971
Peer-review started: January 10, 2018
First decision: January 18, 2018
Revised: February 5, 2018
Accepted: February 8, 2018
Article in press: February 8, 2018
Published online: March 7, 2018
Helicobacter pylori (H. pylori) causes chronic gastritis, gastric and duodenal ulcers, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Disease outcome is related to both host and bacterial factors. Eradication is recommended in all symptomatic patients and those at risk of gastric cancer. However, eradication rates for current therapies are falling due to the emergence of antibiotic resistant H. pylori strains. H. pylori is a highly heterogeneous bacterium and its virulence varies geographically. Virulence factors contribute to the pathogenicity of the bacteria and have been suggested to influence treatment outcome.
In response to the increasing problem of H. pylori antibiotic resistance, local antibiotic resistance surveillance is recommended to guide clinicians in their choice of H. pylori therapy. Knowledge of local antimicrobial resistance rates and the prevalence of virulent infections will influence strategies for optimising the management of H. pylori infection.
This study aimed to provide an update on the prevalence of antibiotic resistance in Ireland, in particular for the antibiotics clarithromycin and fluoroquinolones. The virulence of the infecting strains was assessed by investigating cagA and vacA status. In addition the relationship between virulence factor status and antibiotic resistance was evaluated.
DNA was extracted from antral and corpus biopsies obtained from H. pylori-infected patients. Genotyping for clarithromycin and fluoroquinolone-mediating mutations was performed using the Genotype HelicoDR assay. CagA and vacA genotypes were investigated using PCR and agarose gel electrophoresis.
Primary resistance to clarithromycin was high at 50.5%. Primary resistance to fluoroquinolones was 15.2%. Primary resistance to both antibiotics was 12.4%. A cagA-positive genotype was detected in 22.4% of patient samples. The dominant vacA genotype was S1/M2 at 44.8%, followed by S2/M2 at 26.7%, S1/M1 at 23.6% and S2/M1 at 4.8%. Primary clarithromycin resistance was significantly lower in cagA-positive strains than in cagA-negative strains (32% vs 56.3%). Similarly, in patients infected with more virulent H. pylori strains bearing the vacA s1 genotype, primary clarithromycin resistance was significantly lower than in those infected with less virulent strains bearing the vacA s2 genotype, (41% vs 77.8%). In summary, genotypic H. pylori clarithromycin resistance is high and cagA-negative strains are dominant in our population. Less virulent (cagA-negative and vacA S2-containing) strains of H. pylori are associated with primary clarithromycin resistance.
Given the high rate of primary clarithromycin resistance detected in our study, the use of alternatives to clarithromycin-based triple therapy should be considered for first line H. pylori treatment in our cohort. In order to validate the association between less virulent strains and clarithromycin resistance, the influence of virulence factor genotype on treatment outcome should be assessed.