Comparison of new and classical point mutations associated with clarithromycin resistance in Helicobacter pylori strains isolated from dyspeptic patients and their effects on phenotypic clarithromycin resistance

Kocazeybek, Bekir; Sakli, Merve Kutlu; Yüksel, Pelin; Demırci, Mehmet; Caliskan, Reyhan; Sarp, Tevhide Ziver; Demiryas, Süleyman; Kalaycı, Fatma; Çakan, Hüseyin; Uysal, Hayriye Kırkoyun; Gareayaghi, Nesrin; Erǧin, Sevgi; Erzın, Yusuf; Bal, Kadir; Taşçı, İhsan; Tokman, Hrisi Bahar

doi:10.1099/jmm.0.000944

Cited by 19 publications

(17 citation statements)

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“…In addition, clarithromycin, metronidazole, levofloxacin, tetracycline, and amoxicillin resistance rates range between 18-34%, 28.7-56%, 0-22%, 0-10%, and 0-14%, respectively, in different regions of the world [13,16,[39][40][41], and are 3. [27,[44][45][46]. In a previous study carried out in Bursa province, which is also the location of the present study, the rates of clarithromycin, metronidazole, tetracycline, and amoxicillin resistance were found to be 41.9%, 41.9%, 3.2%, and 3.2%, respectively [14] ( Table 3).…”

Section: Discussionsupporting

confidence: 52%

Detection of Helicobacter pylori by invasive tests in adult dyspeptic patients and antibacterial resistance to six antibiotics, including rifampicin in Turkey. Is clarithromycin resistance rate decreasing?

et al. 2021

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Section: Discussionsupporting

confidence: 52%

Detection of Helicobacter pylori by invasive tests in adult dyspeptic patients and antibacterial resistance to six antibiotics, including rifampicin in Turkey. Is clarithromycin resistance rate decreasing?

et al. 2021

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“…30 A recent study from Turkey reported 33.4% A2142G and 45.8% of A2143G in clarithromycin resistance isolates. 5 Conversely, data from US studies reported the high frequency of A2142G (53%) as compared to A2143G (45%). 31 The clinical importance of these mutations has been studied extensively.…”

Section: Discussionmentioning

confidence: 93%

“…4 Other mutations like A2142C, G1939A, A2115G, G2141A, A2144G, A2144T, C2147G, T2182C, G2224A, and T2215C vary geographically and found to mediate resistance phenotype. 1,3,5 This study on the characterization of 23S rRNA gene mutations in clinical isolates of H. pylori in Pakistan found three new features of domain V. First, a new MboII RFLP pattern was found. Second, 1.2 kb long amplicons of domain V instead of 1.4 kb with a specific primer set were obtained.…”

Section: Introductionmentioning

confidence: 90%

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Characterization of Domain V Mutations in Clinical Isolates of Helicobacter pylori in Pakistan and Their Effect on Clarithromycin MIC

Anis¹,

Niaz²

2021

IDR

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Purpose: Clarithromycin is commonly prescribed for H. pylori infection. Domain V mutations are responsible for clarithromycin resistance. This study was aimed to characterize the clarithromycin resistance and its associated mutations in clinical isolates of H. pylori in Pakistan. Materials and Methods: Infection was diagnosed in 93 patients' biopsies using culture, rapid urease test, 16S rRNA, and vacA gene multiplex PCR. Clarithromycin resistance was assessed by the agar dilution method. Mutations were detected by PCR-RFLP using 46 (1.4 kb) domain V fragments. Sequencing was executed for 13 domain V fragments, of which 12 showed unusual amplicon size (1.2 kb) and 01 had a new MboII RFLP pattern. Results: A total of 48 (83%) strains were obtained from 58 (62.3%) PCR H. pylori-positive samples. Resistance (MIC ≥ 0.001 mg/mL) and intermediate resistance phenotype (MIC = 0.0005 mg/mL) was observed in 22 (46%), and 10 (21%) isolates, respectively. The primary resistance was found in 23 (39.6%) samples. PCR-RFLP detected A2142G, A2143G, and double mutations in 19, 04, and 01 resistant strain, respectively. Sequencing of 10 amplicons obtained from intermediated resistant strains and 03 amplicons from resistant strains showed 138 new mutations. Among them, T2182C was also seen in 04 intermediated resistant isolates, whereas A2142G, A2143G, and A2143C were observed in resistant isolates. The new MboII RFLP pattern in an intermediated resistant strains was due to A1761G mutation. Conclusion: H. pylori domain V mutations showed extensive diversity. Multiple mutations in domain V may give endurance to H. pylori against clarithromycin. Further investigations on the molecular mechanism of antibiotic resistance in H. pylori seem crucial at this stage.

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“…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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Comparison of new and classical point mutations associated with clarithromycin resistance in Helicobacter pylori strains isolated from dyspeptic patients and their effects on phenotypic clarithromycin resistance

Cited by 19 publications

References 28 publications

Detection of Helicobacter pylori by invasive tests in adult dyspeptic patients and antibacterial resistance to six antibiotics, including rifampicin in Turkey. Is clarithromycin resistance rate decreasing?

Detection of Helicobacter pylori by invasive tests in adult dyspeptic patients and antibacterial resistance to six antibiotics, including rifampicin in Turkey. Is clarithromycin resistance rate decreasing?

Characterization of Domain V Mutations in Clinical Isolates of Helicobacter pylori in Pakistan and Their Effect on Clarithromycin MIC

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

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