Elsevier

Gene Reports

Volume 24, September 2021, 101275
Gene Reports

High prevalence of clarithromycin resistant Helicobacter pylori in Turkish children with gastric disorders

https://doi.org/10.1016/j.genrep.2021.101275Get rights and content

Highlights

  • Helicobacter pylori (H. pylori) is one of the leading causes of most gastroduodenal diseases.

  • This study is aimed to survey clarithromycin-resistant H. pylori infection in children with gastric disorders in Turkey.

  • Our findings highlight a high rate of resistance to clarithromycin in Turkish children with H. pylori infection.

Abstract

Objectives

Helicobacter pylori (H. pylori) is one of the leading cause of most gastroduodenal diseases. Commonly, clarithromycin is prescribed to treat H. pylori infections. Increasing resistance to clarithromycin is now one of the main problems of health worldwide. This study is aimed to survey clarithromycin resistant H. pylori infection in children with gastric disorders in Turkey.

Patients and methods

A total of 110 biopsy samples were collected from the gastric antral of children referred to Balcali Hospital in Adana city, Turkey from October 2015 to November 2016. After the DNA extraction, a PCR reaction was performed for the detection of glmM gene as a diagnostic marker for Helicobacter. To examine resistance to clarithromycin, RFLP-PCR was performed to detect A2142G and A2143G point mutations in the 23SrRNA amplification product.

Results

Based on histopathological and RUT tests and PCR, H. pylori was detected in 26.4% (29/110), 23.6% (26/110), and 33.6% (37/110) of the pediatric patients respectively. The frequency of H. pylori infection was dependent on age but independent of gender. The A2143G and A2142G point mutations were found in (n: 13, 61.90%) and (n: 8, 38.09%) of H. pylori isolates.

Conclusion

Our findings highlight a high rate of resistance to clarithromycin in Turkish children with H. pylori infection. Hence, it is essential to note other classes of antibiotics except clarithromycin for the effective treatment of H. pylori infection in children younger than 18 years in the study region.

Introduction

Helicobacter pylori (H. pylori) is a Gram-negative microaerophilic spiral-shaped bacterium that is colonized in the gastric mucosa of almost 30%–50% of healthy individuals (Li et al., 2018). H. pylori infection is usually presented as dyspepsia, peptic ulcer disease, chronic gastritis, and sometimes stomach cancer and extragastric diseases (Take et al., 2015). It is essential, the eradication of H. pylori to control related infections (Zagari et al., 2018; Montazer-Saheb et al., 2011). PCR procedure through the detection of UreC (glmM) gene as a housekeeping gene is now known as an effective method to identify H. pylori infections independent of sample quality and culturing limitations (Shetty et al., 2017). In this respect, clarithromycin as a proton pump inhibitor (PPI) is often used to treat H. pylori infections (Malfertheiner et al., 2017). Clarithromycin by binding to bacterial 23S ribosomal subunit inhibits ribosome protein synthesis.

However, the spread of antibiotic-resistant H. pylori strains has limited the utilization of clarithromycin (Chey et al., 2017). Based on reports, the resistance rate to clarithromycin varies in different geographic areas, such as 37% in North America, 50% in China, 30% in Japan and Italy, and 17.5% to 23.4% in Europe and 40% in Turkey (Thung et al., 2016; Agudo et al., 2010).

In most cases, resistance to clarithromycin appears through point mutations in the domain V of 23SrRNA subunit of H. pylori. A conformation change occurs in the target site of clarithromycin so it can not stop the protein synthesis in the bacterial cell (Megraud et al., 2013). The most common mutations in the 23SrRNA gene are A-to-G transition at location 2142 (A2142G) and A-to-G transition at location 2143 (A2143G) (Kim et al., 2002). Restriction fragment length polymorphism (PCR- RFLP) is known as a fast and accurate method for detecting clarithromycin resistant H. pylori strains through the detection of the mutations in the 23S rRNA gene (Klesiewicz et al., 2014). The purpose of this study was to examine the prevalence rate of H. pylori and resistance to clarithromycin in pediatric patients by the PCR-RFLP technique.

Section snippets

Subjects and samples

A cross-sectional study was performed from October 2015 to November 2016 in the Pediatric Center of the Balcali Hospital, Adana, Turkey. Each of the patient's parents signed an informed consent approved by the research ethics committee. The biopsy samples were obtained from the gastric antrum of patients with digestive disorders by esophagogastroduodenoscopy. Patients with gastritis, ulcer, nodular gastritis, pangastritis, and hyperemia were included in this study. In total, 110 patients

Results

The prevalence of H. pylori was examined in patients with gastric disorders. Based on the results, the prevalence of H. pylori was considerably associated with mild gastritis, pangastritis, and nodular gastritis (p < 0.05) (Table 1).

The prevalence rate of H. pylori infection was assessed based on three methods including RUT, PCR, and histopathological tests. Based on the RUT test, H. pylori bacteria were detected in 23.6% (26/110) of samples while 26.4% (29/110) of biopsy samples were positive

Discussion

In this study, the resistance to clarithromycin was evaluated in pediatric patients in the Adana city of Turkey. According to our results, 33.6% of the patients were positive for H. pylori which 56.75% of them were resistant to clarithromycin consistent with the previous study done in Turkey in 2003 (Bağlan and Özden, 2003). The prevalence of helicobacter in this study was more than the previous studies in Turkey (Maçin et al., 2015; Özçay et al., 2004; Kocazeybek et al., 2019). Despite this,

Conclusion

According to our data, clarithromycin may be unsuitable as the first-line antibiotic for the eradication of H. pylori in pediatric patients in the south of Turkey. Hence, it is essential to note other classes of antibiotics except clarithromycin for the effective treatment of H. pylori infection in children younger than 18 years in the study region.

Ethics committee approval

Tabriz University of Clinical Research Ethics Committee, (reference number: IR. TBZMED. REC.1396, 235).

CRediT authorship contribution statement

Ali Bahadori: Conceptualization. Tülin Güven Gökmen: Data curation. Fatih Köksal: Writing – original draft. Gökhan Tumgor: Visualization. Mehmet Agin: Investigation. Ali Sadighi: Software. Mojtaba Ziaee: Methodology. Leila Rahbarnia: Supervision, Writing – review & editing.

Declaration of competing interest

The authors have no conflict of interest.

Acknowledgment

This study was supported by the Department of Medical Microbiology, Cukurova University, Adana, Turkey, and Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. The authors are very grateful to the Balcali Hospital endoscopy unit staff for their valuable help and cooperation during this study.

References (28)

  • S. Agudo et al.

    High prevalence of clarithromycin-resistant Helicobacter pylori strains and risk factors associated with resistance in Madrid, Spain

    J. Clin. Microbiol.

    (2010)
  • M. Amin et al.

    Assessment of metronidazole and clarithromycin resistance among Helicobacter pylori isolates of Ahvaz (southwest of Iran) during 2015-2016 by phenotypic and molecular methods

    Jundishapur J. Microbiol.

    (2019)
  • P. Bağlan et al.

    Helicobacter pylori’nin antibiyotiklere direnci

    Güncel Gastroenteroloji.

    (2003)
  • W.D. Chey et al.

    ACG clinical guideline: treatment of Helicobacter pylori infection

    Am. J. Gastroenterol.

    (2017)
  • V. De Francesco et al.

    Clarithromycin-resistant genotypes and eradication of Helicobacter pylori

    Ann. Intern. Med.

    (2006)
  • T. Essawi et al.

    Determination of Helicobacter pylori virulence genes in gastric biopsies by PCR

    ISRN Gastroenterol.

    (2013)
  • E. Ierardi et al.

    How antibiotic resistances could change Helicobacter pylori treatment: a matter of geography?

    World J Gastroenterol: WJG

    (2013)
  • S. Kato et al.

    The prevalence of Helicobacter pylori in Japanese children with gastritis or peptic ulcer disease

    J. Gastroenterol.

    (2004)
  • K.S. Kim et al.

    Mutations in the 23S rRNA gene of Helicobacter pylori associated with clarithromycin resistance

    J. Korean Med. Sci.

    (2002)
  • K. Klesiewicz et al.

    PCR-RFLP detection of point mutations A2143G and A2142G in 23S rRNA gene conferring resistance to clarithromycin in Helicobacter pylori strains

    Acta Biochim. Pol.

    (2014)
  • B. Kocazeybek et al.

    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

    J. Med. Microbiol.

    (2019)
  • J.Y. Lee et al.

    Diagnosis of Helicobacter pylori by invasive test: histology

    Ann. Transl. Med.

    (2015)
  • M. Li et al.

    Systematic review with meta-analysis: vonoprazan, a potent acid blocker, is superior to proton-pump inhibitors for eradication of clarithromycin-resistant strains of Helicobacter pylori

    Helicobacter.

    (2018)
  • C. Lu et al.

    Systematic review of the relationship of Helicobacter pylori infection with geographical latitude, average annual temperature and average daily sunshine

    BMC Gastroenterol.

    (2018)
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