AUTHOR=Kim Jewel J., Kocsmár Ildikó , Buzás György M., Szirtes Ildikó , Rusz Orsolya , Diczházi Csaba , Szijártó Attila , Hritz István , Schaff Zsuzsa , Kiss András , Kocsmár Éva , Lotz Gábor 

TITLE=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

JOURNAL=Pathology and Oncology Research

VOLUME=27

YEAR=2021

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2021.1609863

DOI=10.3389/pore.2021.1609863

ISSN=1532-2807

ABSTRACT=<p>The global rise in clarithromycin (Cla) resistance is considered to be the main contributor of <italic>Helicobacter pylori</italic> (<italic>Hp</italic>) eradication failures. In nearly half of the Cla-resistant <italic>Hp</italic> infections, Cla-susceptible bacteria are simultaneously present with the Cla-resistant ones (Cla-heteroresistance). The proportion of resistant bacteria in the bacterial population (R-fraction) and its predictive role for the use of Cla-based therapies in Cla-heteroresistant infections has not yet been investigated. Our retrospective study analyzed gastric biopsy samples of 62 <italic>Hp</italic>-positive patients with Cla-heteroresistant infection. Fluorescence <italic>In Situ</italic> Hybridization technique was used to visualize the coexistence of resistant and susceptible bacteria within one tissue sample. R-fraction was quantified on multichannel microimages by digital morphometry. Resistant bacteria had a patchy distribution within the whole bacterial population causing high diversity among the investigated areas. Patients were subdivided into two major groups according to whether a Cla-based eradication attempt was conducted before or after the biopsy sampling. R-fraction was significantly lower among cases having only one previous Cla-based eradication attempt vs. those that had multiple previous eradications, including at least one Cla-containing therapy (0.41 vs. 0.89, <italic>p</italic> = 0.0308). Majority of the patients without previous eradication attempt had successful eradication with Cla-containing regimen (59.26%), verified by a negative <sup>13</sup>C-urea breath test or control biopsy. Multivariable model indicated that the therapeutic outcome using Cla-based regimens depended on the bacterial density rather than the R-fraction. Our study raises the potential use of Cla-containing eradication therapies in certain Cla-heteroresistant <italic>Hp</italic> infections, taking into account the possible predictive role of bacterial density.</p>