Noninvasive molecular analysis ofHelicobacter pylori: Is it time for tailored first-line therapy?

Abstract

The main problem of Helicobacter pylori (H. pylori) infection management is linked to antibiotic resistances. This phenomenon has grown in the last decade, inducing a dramatic decline in conventional regimen effectiveness. The causes of resistance are point mutations in bacterial DNA, which interfere with antibiotic mechanism of action, especially clarithromycin and levofloxacin. Therefore, international guidelines have recently discouraged their use in areas with a relevant resistance percentage, suggesting first-line schedules with expected high eradication rates, i.e., bismuth containing or non-bismuth quadruple therapies. These regimens require the daily assumption of a large number of tablets. Consequently, a complete adherence is expected only in subjects who may be motivated by the presence of major disorders. However, an incomplete adherence to antibiotic therapies may lead to resistance onset, since sub-inhibitory concentrations could stimulate the selection of resistant mutants. Of note, a recent meta-analysis suggests that susceptibility tests may be more useful for the choice of first than second-line or rescue treatment. Additionally, susceptibility guided therapy has been demonstrated to be highly effective and superior to empiric treatments by both meta-analyses and recent clinical studies. Conventional susceptibility test is represented by culture and antibiogram. However, the method is not available everywhere mainly for methodology-related factors and fails to detect hetero-resistances. Polymerase chain reaction (PCR)-based, culture-free techniques on gastric biopsy samples are accurate in finding even minimal traces of genotypic resistant strains and hetero-resistant status by the identification of specific point mutations. The need for an invasive endoscopic procedure has been the most important limit to their spread. A further step has, moreover, been the detection of point mutations in bacterial DNA fecal samples. Few studies on clarithromycin susceptibility have shown an overall high sensitivity and specificity when compared with culture or PCR on gastric biopsies. On these bases, two commercial tests are now available although they have shown some controversial findings. A novel PCR method showed a full concordance between tissue and stool results in a preliminary experience. In conclusion, despite poor validation, there is increasing evidence of a potential availability of noninvasive investigations able to detect H. pylori resistances to antibiotics. These kinds of analysis are currently at a very early phase of development and caution should be paid about their clinical application. Only further studies aimed to evaluate their sensitivity and specificity will afford novel data for solid considerations. Nevertheless, noninvasive molecular tests may improve patient compliance, time/cost of infection management and therapeutic outcome. Moreover, the potential risk of a future increase of resistance to quadruple regimens as a consequence of their use on large scale and incomplete patient ad...

Helicobacter pylori Eradication According to Sequencing-Based 23S Ribosomal RNA Point Mutation Associated with Clarithromycin Resistance

“…Previous studies using the PCR-Restriction Fragment Length Polymorphism (RFLP) system have shown the high frequency of the A2143G or A2144G mutations in clarithromycin-resistant H. pylori in both the United States and Europe [16,26]. There was no mutation at position 2144 in our study, indicating that the main 23S rRNA gene mutations inducing clarithromycin resistance are dissimilar in western and eastern countries [14]. Moreover, we documented that clinically insignificant point mutations had little influence on the H. pylori eradication rate; however, this has yet to be confirmed and fully elucidated.…”

“…This study has some limitations. First, we could not perform H. pylori culture and antibiotic susceptibility testing [14]. It is reported that there may be discordance between genotype and phenotype [27].…”

“…Recently, there has been increasing evidence of molecular methods for the detection of H. pylori resistance to antibiotics such as clarithromycin and quinolones, which have been commonly used until now [12][13][14]. Dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) assay detects mutational changes in H. pylori obtained from biopsy samples or feces.…”

“…Dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) assay detects mutational changes in H. pylori obtained from biopsy samples or feces. The method is relatively simple and accurate in finding minimal traces of genotypic resistant strains; however, it can only detect A2143G and A2142G mutations [12][13][14].…”

Surveillance of the Antimicrobial Resistance Rates of <b><i>Helicobacter pylori</i></b> Ten Years Later in the Western Central Region, Colombia

“…International guideline agencies have recently rejected the use of clarithromycin in areas with a resistance rate higher than 15%. Nevertheless, guidelines are designed for the clinical practice within an empirical setting, that is, where susceptibility testing is unavailable, epidemiological data are taken in account to allow for the rational use of antibiotics [31]. Before 2007, between the years 1999 and 2006, in the central-western region of Colombia, the resistance to metronidazole, clarithromycin, and amoxicillin was found in 82, 3.8, and 1.9% of 106 H. pylori isolates respectively.…”