Helicobacter pylori heteroresistance to clarithromycin in adults—New data by in situ detection and improved concept

Abstract

BackgroundClarithromycin (Cla) heteroresistance of Helicobacter pylori (H pylori) infections is commonly assessed by comparing the resistance status of antrum and corpus biopsy samples and by demonstrating the discrepancy between them (interniche heteroresistance). However, fluorescence in situ hybridization (FISH) technique is capable of showing the synchronous presence of susceptible and resistant bacteria (intraniche heteroresistance), enabling the detection of heteroresistant H pylori populations within one biopsy sample.Materials and MethodsAntrum and corpus biopsy specimens of 305 H pylori‐infected patients were investigated with an rRNA‐targeted Cla‐resistance FISH test. Anamnestic data were collected from the institutional electronic register. Prevalence rates of susceptible, homo‐ and heteroresistant cases were correlated with the anamnestic and clinicopathological data.ResultsOverall Cla‐resistance rate was 23.9% (73 cases), consisting of 35 (11.5%) homoresistant and 38 (12.5%) heteroresistant cases. Thirty‐five patients had at least one biopsy site where susceptible and resistant bacteria were present simultaneously. From this subset, 20 cases demonstrated intraniche heteroresistance on both sites. Prior Cla‐based eradication attempts were more frequent in homoresistant than in susceptible and heteroresistant cases (P < .001, P < .001, respectively). Cla‐containing therapy eradicated heteroresistant infections at a significantly lower rate in comparison with susceptible cases (P = .0112), but more effectively than homoresistants (P = .0393).ConclusionsThe most frequent type of Cla‐heteroresistance is the coexistence of susceptible and resistant H pylori bacteria in the same location (intraniche heteroresistance). A previous Cla‐based eradication attempt predisposes patients to homoresistant infection. Heteroresistance is characterized by a non‐eradication‐related background and intermediate characteristics in many respects when compared to susceptible and homoresistant cases.

Antimicrobial resistance of Helicobacter pylori in an eastern German region

“…In 22 samples, we detected H pylori both susceptible and resistant to clarithromycin and levofloxacin, respectively. Patients with such a heteroresistant status still may benefit from clarithromycin‐ and/or levofloxacin‐based eradication treatments when compared with patients carrying exclusively resistant bacteria 15‐17 . An impact on eradication success may also depend on the kind of mutation.…”

Efficacy of Clarithromycin Depends on the Bacterial Density in Clarithromycin-Heteroresistant Helicobacter pylori Infections: An In Situ Detected Susceptibility and Quantitative Morphometry-Based Retrospective Study

“…Given the limited number of cases and the retrospective nature of the study, our results should be considered somewhat preliminary and will require further confirmation. Based on our previous publications, it is clear that heteroresistant H. pylori infections account for about half of all clarithromycin-resistant cases (18,38). Therefore, further prospective studies with increased patient case number would be necessary to establish a more definite relationship between eradication success and bacterial load, as well as, to find further predictive factors to facilitate therapeutic decisions, and in result contribute to establishing a standard protocol for Cla-heteroresistant infections.…”

“…Cla-heteroresistance is frequent, but the currently used routine diagnostic susceptibility test methods (E-test, PCR, or the combination) are set to diagnose interniche heteroresistance only, which may undermine the actual heteroresistance rates (17,18,20,(26)(27)(28)(29)(30). In a previous study of our group, by applying FISH technique to gastric biopsy specimens, we demonstrated that the heteroresistance occurs in more than half (52%) of the Cla-resistant H. pylori infections (18). The most common form was found to be the intraniche heteroresistance occurring simultaneously in the antrum and the corpus of the stomach.…”

“…These widely used H. pylori Cla-resistance detection methods are however not adapted to reveal intraniche heteroresistance, represented by the coexistence of susceptible and resistant microbes in the same gastric mucosal site (16,17), as they only give a yes or no result in routine settings. Another manifestation of heteroresistance is known as interniche heteroresistance, where isolates with different resistance attributes (susceptible, resistant, or mixed) are found within different sites of the stomach, resulting in an underestimation of the actual antimicrobial resistance, as it is difficult to detect resistance when the isolates are not uniformly distributed in the gastric mucosa (16)(17)(18). Fluorescence in situ hybridization (FISH) method is capable of revealing individual H. pylori bacteria carrying Claresistance causing point mutations (19), as well as visualizing the coexistence of susceptible and resistant bacteria within one biopsy sample (18,20).…”

“…Our research group has recently published an improved concept on H. pylori heteroresistance, proposing that Cla-heteroresistant cases form a distinct subgroup of the H. pylori infections with intermediate characteristics compared to the susceptible and homoresistant cases. Accordingly, unlike homoresistant infections, heteroresistant infections are not closely related to prior unsuccessful eradication attempts, and H. pylori eradication with clarithromycin-containing regimens might be successful in more than half of the Cla-heteroresistant infections ( 18 ).…”