Prospective, multicenter clinical trial on inter- and intra-patient genetic variability for antimicrobial resistance of Helicobacter pylori

Objectives:

We conducted a large prospective, multicenter clinical investigation on the antimicrobial resistance of H. pylori strains against clarithromycin and quinolones in Austria.

Methods:

A total of 2004 therapy-naïve patients from all geographic regions of Austria were included. Gastric biopsy samples were collected individually from antrum and corpus during routine endoscopy from 2015 to 2016, and analyzed histopathologically for H. pylori infection. Resistance to clarithromycin and quinolones was evaluated in H. pylori-positive samples by highly sensitive PCR assays. Clinical and demographic information was correlated to resistance patterns.

Results:

H. pylori infection was detected in 514 of 2004 patients (26%) by histopathology. The infection was confirmed in 465/514 (90%) patients by real-time PCR. Discordant PCR results were found for antrum and corpus in 6% (27/465), indicating a patchy infection of the gastric mucosa. Clarithromycin-resistance rates were 17% and 19%, and quinolone-resistance rates were 12% and 10% in antrum and corpus samples, respectively, indicating also a patchy distribution of different H. pylori strains. Combination of test results per patient yielded resistance rates of 21% and 13% for clarithromycin and quinolones, respectively. Overall, the rate of mixed infections with respect to markers of resistance was 14% (65/465). Resistance to both antimicrobials tested was detected in 2% (9/383) of patients. Clarithromycin-resistant H. pylori strains were significantly more frequently found in females (p = 0.033).

Conclusion:

Multiple sampling in endoscopy increases the likelihood of H. pylori detection and identification of resistant strains in mixed infections. Clarithromycin-resistance is high (21%) in Austria, however not as high as previously published in a European study (37%). Alternative strategies to standard combination treatment with clarithromycin are required such as microbiological resistance testing or alternative empiric treatment regimens. Considering the very low multiple-resistance rate, combination treatment regimens of clarithromycin and quinolones may be a good option for first-line eradication therapy in Austria.