No benefit with genotypic resistance-guided therapy for refractory H. pylori
Genotypic resistance-guided therapy is no better than traditional empiric therapy for treating patients with refractory Helibacter pylori infection. Researchers found no significant difference in eradication rate between the two strategies when used in the third-line setting.
“We can consider empiric therapy, according to prior eradication regimens, as an alternative treatment strategy for H. pylori infection if antibiotic susceptibility testing is not available,” commented lead investigator Dr Po-Yueh Chen of the Ditmanson Medical Foundation Chia-Yi Christian Hospital in Chia-Yi, Taiwan, who spoke at the Asian Pacific Digestive Week 2017 held recently in Hong Kong.
Antibiotic resistance has hindered the use of eradication therapy for patients with H. pylori infection. Treatment strategies based on antimicrobial resistance has become routine in refractory patients as empiric therapy becomes less effective in the presence of multidrug resistance. Around 5 percent of patients with H. pylori infection will require third-line treatment.
The Maastricht V Consensus guidelines currently recommend third-line treatment based on culture-based susceptibility testing, genotypic resistance-guided therapy or empiric therapy based on prior treatment regimens, while The Toronto Consensus guidelines recommend empiric therapy based on prior eradication regimens only. [Gut 2017;66:6-30; Gastroenterology 2016;151:51-69.e14]
“However, the strengths of both treatment recommendations are weak, and there remains many limitations in traditional susceptibility testing,” said Chen. “For one, little is known about how to select appropriate antibiotics even if the susceptibility test results are available.”
To overcome these limitations, Chen and colleagues assessed the efficacy of genotypic resistance-guided therapy vs empiric therapy in a multicentre, randomized controlled trial involving 410 patients with persistent H. pylori infection who had failed at least two prior lines of treatment.
For patients randomized to receive genotypic resistance-guided therapy, levofloxacin-based sequential therapy was given for those with no mutations present in the genes encoding for gyrase A, clarithromycin-based sequential therapy was given for those positive for mutations in gyrase A and negative for mutations in the 23S ribosomal RNA (rRNA), and tetracycline-based sequential therapy was given for those with both gyrase A and 23S rRNA mutations. Similarly, patients randomized to receive empiric therapy were given levofloxacin-, clarithromycin- or tetracycline-based sequential therapy based on their prior treatment history.
Following the 14-day treatment regimens, patients receiving genotypic resistance-guided therapy in the intention-to-treat analysis achieved an eradication rate of 78.2 percent, while those receiving empiric therapy achieved an eradication rate of 72.5 percent. In the per-protocol analysis, the eradication rate was 78.9 percent in the genotypic resistance-guided therapy arm vs 74.7 percent in the empiric therapy arm.
“This is the first randomized controlled trial to show that genotypic resistance-guided therapy is not significantly superior to empiric therapy by more than 10 percent after two or more eradication failures,” concluded Chen.