Primary and secondary clarithromycin resistance in Helicobacter pylori and mathematical modeling of the role of macrolides

Kocsmár, Éva; Buzás, György Miklós; Szirtes, Ildikó; Kocsmár, Ildikó; Kramer, Zsófia; Szíjártó, Attila; Fadgyas-Freyler, Petra; Szénás, Kató; Fassan, Matteo; Kiss, András; Schaff, Zsuzsa; Röst, Gergely; Lotz, Gábor

doi:10.1038/s41467-021-22557-7

Cited by 41 publications

(35 citation statements)

References 45 publications

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“…In this study, we showed that female patients had a higher retreatment rate than male, and patients with duodenal ulcer had a lower retreatment rate, which were in accordance with previous studies 29–31 . Our study also showed that the triple therapy containing metronidazole had a significantly higher retreatment rate as compared to therapy containing amoxicillin, and the longer treatment duration for 14 days was associated with a lower retreatment rate.…”

Section: Discussionsupporting

confidence: 91%

Age of eradication and failure rates of clarithromycin‐containing triple therapy forHelicobacter pylori: A 15‐year population‐based study

et al. 2022

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Background Failure rates of clarithromycin‐containing triple therapy for H. pylori are rising. To determine the trend of failure rates of clarithromycin‐containing triple therapy in different age groups in Hong Kong over the past 15 years. Materials and Methods This is a population‐based retrospective age‐period‐cohort study involving all adult H. pylori‐infected patients who had received the first course of clarithromycin‐containing triple therapy in 2003–2017. Failed eradication was identified by the need of retreatment within 2 years of eradication. Logistic regression model was used to characterize the risk of retreatment. Results 113,526 H. pylori‐infected patients were included. The overall failure rate increased from 4.83% in 2003 to 10.2% in 2016 (p for linear trend <0.001). When stratified by age of eradication, patients 75 years or above had the lowest retreatment rate of 5.11%, which progressively increased in younger patients (60–74 years: OR 1.26, 95% CI 1.15–1.38; 45–59 years: OR 1.36, 95% CI 1.24–1.48; 18–44 years: OR 1.55, 95% CI 1.41–1.69). The results remained consistent when stratified by year of birth, and period of eradication. Other risk factors for retreatment included female (OR 1.24, 95% CI 1.18–1.30), triple therapy containing metronidazole (OR 2.30, 95% CI 2.12–2.50), and shorter duration of therapy (10 days: OR 0.88, 95% CI 0.79–0.97; 14 days: OR 0.67, 95% CI 0.58–0.77 vs 7 days). Conclusions While failure rates of clarithromycin‐containing triple therapy progressively increased over the past 15 years, the failure rate was particularly high among younger patients, which could undermine the potential benefits of early H. pylori eradication.

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Section: Discussionsupporting

confidence: 91%

Age of eradication and failure rates of clarithromycin‐containing triple therapy forHelicobacter pylori: A 15‐year population‐based study

et al. 2022

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…However, since this phenomenon affects the individual images equally, it did not cause a bias in the intrapatient and intragroup comparisons. Moreover, as the FISH technique used only detects the three most frequent point mutations of 23S rRNA, the resistance caused by less common genetic mechanisms may have been missed (38)(39)(40)(41)(42). In addition, we did not have the information regarding the resistance to other antibacterial components (e.g.…”

Section: Discussionmentioning

confidence: 99%

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

Kim

Kocsmár

Buzás³

et al. 2021

Pathol. Oncol. Res.

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The global rise in clarithromycin (Cla) resistance is considered to be the main contributor of Helicobacter pylori (Hp) eradication failures. In nearly half of the Cla-resistant Hp 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 Hp-positive patients with Cla-heteroresistant infection. Fluorescence In Situ 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, p = 0.0308). Majority of the patients without previous eradication attempt had successful eradication with Cla-containing regimen (59.26%), verified by a negative 13C-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 Hp infections, taking into account the possible predictive role of bacterial density.

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“…This is explained (correctly) by the authors as due to unintended H. pylori eradication with antibiotics for another disease. This possibility is supported by a further study by us, which for the first time described the population dynamics of H. pylori clarithromycin resistance using mathematical modelling [ 5 ]. In the cohort of this study, 1731 of 4744 H. pylori infected individuals (36.5%) had a history of prior non-eradication macrolide treatment.…”

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confidence: 87%

Comment on Skrebinska et al. Who Could Be Blamed in the Case of Discrepant Histology and Serology Results for Helicobacter pylori Detection? Diagnostics 2022, 12, 133

Kocsmár

Lotz

2022

Diagnostics

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In their article, Skebrinska and colleagues analysed the potential pitfalls of detecting Helicobacter pylori (H. pylori) by serology, histological (Giemsa) and immunohistochemical (IHC) staining. However, in the Introduction, the authors state: “…IHC is recommended only in individuals with active gastritis without H. pylori identification by histochemistry”. Although this is a widely-held view, it does not seem to hold up in view of the results of the study by Kocsmár et al., which showed that the diagnostic sensitivity of Giemsa in the absence of activity is only 33.6%, but it is 92.6% in the presence of active gastritis, which is close to the 99.4% sensitivity of IHC. Considering that chronic active gastritis with the features of H. pylori gastritis is also common in other entities, if active inflammation is present in the sample, there is a very small chance that a Giemsa-negative case will be confirmed as H. pylori-positive by IHC. Based on this, the use of IHC is more reasonable in Giemsa-negative cases with no activity in which the etiological role of H. pylori is suggested by clinical, anamnestic or other data. However, it may also be reasonable to routinely use IHC as the primary staining method instead of Giemsa.

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Primary and secondary clarithromycin resistance in Helicobacter pylori and mathematical modeling of the role of macrolides

Cited by 41 publications

References 45 publications

Age of eradication and failure rates of clarithromycin‐containing triple therapy forHelicobacter pylori: A 15‐year population‐based study

Age of eradication and failure rates of clarithromycin‐containing triple therapy forHelicobacter pylori: A 15‐year population‐based study

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

Comment on Skrebinska et al. Who Could Be Blamed in the Case of Discrepant Histology and Serology Results for Helicobacter pylori Detection? Diagnostics 2022, 12, 133

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