Phenotypic and genotypic Helicobacter pylori clarithromycin resistance and therapeutic outcome: benefits and limits

Francesco, Vincenzo De; Zullo, Angelo; Ierardi, Enzo; Giorgio, Floriana; Perna, Federico; Hassan, Cesare; Morini, Sergio; Pañella, C.; Vaira, Dino

doi:10.1093/jac/dkp445

Cited by 99 publications

(85 citation statements)

References 31 publications

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“…However, some differences between phenotype and genotype profiles were observed; these were characterized by phenotypic susceptibility and genotypic resistance or vice versa, in contrast to other studies [22][23][24].…”

Section: Discussioncontrasting

confidence: 86%

Phenotypic and genotypic correlation as expressed in Helicobacter pylori resistance to clarithromycin and fluoroquinolones

Binyamin

Pastukh

et al. 2017

Gut Pathog

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Background:Helicobacter pylori susceptibility to clarithromycin and fluoroquinolone can be determined through Etest or molecular assays. We examined the correlation between phenotypic susceptibility (MIC results) and genotypic susceptibility in H. pylori strains isolated from gastric biopsies. Results:Out of 85 duplicate biopsies obtained from patients from northern Israel who underwent endoscopy, 70 were positive for H. pylori using the CUTest (urease test). These biopsies were cultured for H. pylori and Etest breakpoints were determined for levofloxacin and clarithromycin. H. pylori detection, characterization of wild type (WT) or mutant alleles, and antibiotic resistance were determined molecularly using GenoType HelicoDR kit. Phenotypic and genotype results were compared. The molecular method had higher sensitivity for detection of H. pylori than culture (94.3% vs. 77.1%). Resistance to clarithromycin was higher than to levofloxacin by both methods. Levofloxacin resistance was found in 21.2 and 0% using genotypic and phenotypic methods, respectively. Clarithromycin resistance was found in 66.7 and 62.9% by genotypic and phenotypic methods, respectively. Some samples were found susceptible by Etest and resistant by GenoType HelicoDR (13/53 samples) and some vice versa (10/53 samples). Conclusion:GenoType HelicoDR kit has high sensitivity rate for H. pylori detection. It has the ability to detect many mutations and can help to determine initial antibiotic treatment at the beginning of therapy. However, there were a few cases where there was a phenotype-genotype mismatch result that could derive from possible causes. For example, a resistance mechanism that is not tested in the kit.

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Section: Discussioncontrasting

confidence: 86%

Phenotypic and genotypic correlation as expressed in Helicobacter pylori resistance to clarithromycin and fluoroquinolones

Binyamin

Pastukh

et al. 2017

Gut Pathog

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“…Notably, the eradication rate showed the lowest value (30.7%) when the phenotypic bacterial resistance was genetically linked to the A2143G point mutation. The conclusion of this study was that there is a disagreement between the two methods; clarithromycin resistance markedly reduces H. pylori eradication only when it is linked to a specific point mutation [26] . On these grounds, it has been suggested that MIC values for clarithromycin resistance should be dropped to 0.5 in order to improve the efficacy of phenotypic detection [27] .…”

Section: Methods For Clarithromycin Resistance Detectionmentioning

confidence: 89%

Primary clarithromycin resistance toHelicobacter pylori: Is this the main reason for triple therapy failure?

Giorgio

Principi²,

Francesco³

et al. 2013

WJGP

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“…In particular, point mutations at positions 2143 (A to G) and 2142 (A to G or C) are responsible for Ͼ90% of clarithromycin resistance cases (9). Moreover, the presence of the A2143G mutation is strongly associated with eradication therapy failure (10,11). A lower prevalence of the A2142G/C mutation has been reported (11), but these mutations are also commonly found in patients for whom clarithromycin-based treatment failed to eradicate the infection.…”

mentioning

confidence: 99%

A Novel Stool PCR Test for Helicobacter pylori May Predict Clarithromycin Resistance and Eradication of Infection at a High Rate

et al. 2017

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Clarithromycin-based regimens are commonly used as a first-line therapy for Helicobacter pylori-positive patients; however, resistance to clarithromycin has led to treatment failures. The aim of this study was to evaluate the feasibility of using stool samples to detect the presence of H. pylori DNA while concurrently detecting mutations associated with resistance to clarithromycin. For this purpose, total DNA was extracted from 294 raw stool specimens from H. pylori-positive and -negative patients. TaqMan real-time PCR amplification was used to detect the presence of H. pylori as well as to predict the phenotype of the organism and the related outcome for patients treated with clarithromycin. Clarithromycin resistance was determined upon analysis of the PCR result. Patients were also tested by a urea breath test and were subjected to esophagogastroduodenoscopy, followed by histology, culture, and a rapid urease test, in order to obtain a consensus patient infection status. Of 294 total stool samples, 227 were deemed true positive. The sensitivity of H. pylori detection by PCR was 93.8%. Of 213 true-positive samples that were sequenced, 36.2% showed point mutations associated with clarithromycin resistance (A2142C, A2142G, A2143G). The final correlation of the mutant genotypes as determined by sequencing with the eradication of infection was 86%. We found that Helicobacter pylori DNA can be detected in human stool specimens with high sensitivity and can therefore be used to determine the presence of the bacterium without obtaining a biopsy sample. Moreover, genotypic resistance to clarithromycin can be predicted without obtaining a biopsy sample, facilitating the choice of the right therapeutic approach.

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Phenotypic and genotypic Helicobacter pylori clarithromycin resistance and therapeutic outcome: benefits and limits

Abstract: This study showed that: (i) there is a relevant discordance between the two methods; and (ii) phenotypic clarithromycin resistance markedly reduces H. pylori eradication when it is linked to a specific point mutation.

Cited by 99 publications

References 31 publications

Phenotypic and genotypic correlation as expressed in Helicobacter pylori resistance to clarithromycin and fluoroquinolones

Phenotypic and genotypic correlation as expressed in Helicobacter pylori resistance to clarithromycin and fluoroquinolones

Primary clarithromycin resistance toHelicobacter pylori: Is this the main reason for triple therapy failure?

A Novel Stool PCR Test for Helicobacter pylori May Predict Clarithromycin Resistance and Eradication of Infection at a High Rate

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