Antimicrobial susceptibility testing for Helicobacter pylori in times of increasing antibiotic resistance

Abstract

The gram-negative bacterium Helicobacter pylori (H. pylori) causes chronic gastritis, gastric and duodenal ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Treatment is recommended in all symptomatic patients. The current treatment options for H. pylori infection are outlined in this review in light of the recent challenges in eradication success, largely due to the rapid emergence of antibiotic resistant strains of H. pylori. Antibiotic resistance is a constantly evolving process and numerous studies have shown that the prevalence of H. pylori antibiotic resistance varies significantly from country to country, and even between regions within the same country. In addition, recent data has shown that previous antibiotic use is associated with harbouring antibiotic resistant H. pylori. Local surveillance of antibiotic resistance is warranted to guide clinicians in their choice of therapy. Antimicrobial resistance is assessed by H. pylori culture and antimicrobial susceptibility testing. Recently developed molecular tests offer an attractive alternative to culture and allow for the rapid molecular genetic identification of H. pylori and resistance-associated mutations directly from biopsy samples or bacterial culture material. Accumulating evidence indicates that surveillance of antimicrobial resistance by susceptibility testing is feasible and necessary to inform clinicians in their choice of therapy for management of H. pylori infection.

Keywords: Antibiotic resistance; Antimicrobial susceptibility testing; Helicobacter pylori; Molecular test; Polymerase chain reaction.

Figure 1

Molecular mechanism of clarithromycin and levofloxacin resistance. A: Clarithromycin binds and suppresses the activity of the bacterial ribosomal subunit, thus inhibiting protein synthesis. Single point mutations within the Helicobacter pylori (H. pylori) rrl gene encoding the 23S ribosomal RNA component of ribosomes result in clarithromycin resistance. The best characterised point mutations conferring clarithromycin resistance are A2146C, A2146G and A2147G; B: Levofloxacin targets H. pylori DNA gyrase. The most significant mutations conferring levofloxacin resistance occur at positions 87 and 91 of the H. pylori gyrA gene, which encodes the A subunit of the DNA gyrase enzyme involved in regulating the topological state of bacterial DNA during replication. CLAR^S: Clarithromycin sensitive; CLAR^R: Clarithromycin resistant; LEVO^S: Levofloxacin sensitive; LEVO^R: Levofloxacin resistant; WT: Wild type; MUT: Mutant.