Editorial: H. pylori Antimicrobial Susceptibility Testing—An Expanding Toolbox

Abstract

Helicobacter pylori (H. pylori) is one of the most common bacterial infections globally and, due to its association with gastric cancer, the leading cause of infection-related malignancy worldwide [1, 2]. Effective eradication of H. pylori has long been challenged by empiric and complicated treatment regimens linked to increasing antimicrobial resistance [3]. Within the UnitedStates, resistance rates to metronidazole, clarithromycin and levofloxacin are 42.1%, 31.5% and 37.6%, respectively [4] leading to a recommendation in the recently published US guidelines against using clarithromycin or levofloxacin unless the strain is known to be sensitive [5].

H. pylori antimicrobial resistance testing is still rarely utilised in routine clinical practice as culture-based testing is slow (often taking one to 2 weeks), often unsuccessful and incontrovertible evidence is still lacking that a ‘tailored’ approach provides superior clinical outcomes over the continuing use of empiric regimens [1]. This is likely to change with the encouragement of more susceptibility testing by national and international authorities [5, 6], and the availability of rapid, sensitive and accurate molecular methods as increasingly used in clinical microbiology practice.

Vasapolli et al. have added to the emerging molecular choices by describing genotypic H. pylori clarithromycin and levofloxacin susceptibility testing by real-time PCR from gastric aspirates harvested at routine upper endoscopy [7]. The results, based on the common gyrase A and 23sRNA mutations that lead to levofloxacin and clarithromycin resistance respectively, [8] were highly concordant with those of conventional phenotypic testing. The rapidity, efficiency and accuracy of this approach could enable endoscopists to both diagnose H. pylori and choose an appropriate regimen based on antimicrobial susceptibility within hours of the procedure.

Gastric aspirate susceptibility testing adds a potential new tool to the growing toolbox of molecular methods, some of which are commercially available. These include biopsy-based PCR, fluorescent in situ hybridisation and next generation sequencing. Stool-based testing (obviating the need for endoscopy) has also been investigated for clarithromycin resistance by PCR as well as for a wider panel of antibiotics by next generation sequencing [9].

Research to this point has demonstrated the feasibility and robustness of these biopsy-dependent or stool-based molecular methods to evaluate H. pylori's susceptibility to clarithromycin and levofloxacin. Resistance to these antibiotics, which is due to a small group of well-defined mutations, is clearly correlated with clinical outcome. Whether molecular testing will be useful for the more complex question of metronidazole resistance remains to be determined [8]. Ultimately, whether H. pylori resistance testing will gain the traction in clinical practice that the experts have deemed to be necessary will depend upon its accuracy, ease of use, cost and demonstration of added value. The gastric aspirate method [7] appears to satisfy the first two of these criteria, thus representing a step towards achieving improved H. pylori eradication rates in routine clinical practice.