Characterization of clarithromycin heteroresistance among Helicobacter pylori strains isolated from the antrum and corpus of the stomach
Mixed infections and heteroresistance of Helicobacter pylori contribute to decreased efficacy of treatments. This study aimed to investigate frequency of clarithromycin heteroresistance and its link with mixed infections, medication history, and disease severity. A total of 40 pairs of H. pylori strains were isolated from the antrum and corpus of 97 patients. Susceptibility of the strains to clarithromycin was measured by agar dilution method. Site-specific mutations of 23S rRNA at A2143G, A2142G, and A2142C positions were analyzed by PCR and genomic relatedness of pairs of the strains was determined by random amplified polymorphic DNA (RAPD)-PCR. The results showed a prevalence of 35% (14/40) clarithromycin resistance. Diversity of the antrum and corpus isolates in resistance to clarithromycin was detected among 17.5% (7/40) of the patients. Similarly, diversity in MIC value was also detected in two patients infected with the sensitive strains. Significant difference in frequency of resistance was detected among patients with peptic ulcer disease (PUD) (MIC90 32 μg/mL) and severe gastritis (MIC90 16 μg/mL), compared with those who suffered from non-ulcer dyspepsia (NUD) (MIC90 8 μg/mL) and chronic gastritis (MIC90 0.25 μg/mL). MIC values showed 8–32 folds increased levels in the corpus. A2142G, A2143G, and A2142C mutations were detected in three, two, and two patients, respectively, but not observed in 46% of the resistant strains. RAPD-PCR fingerprints showed identical molecular patterns for the isolates of the corpus and antrum in each patient. In conclusion, microevolution of H. pylori strains during chronic infection, rather than mixed infection, and inappropriate medication appear to be main reasons of treatment failure in adults.
The authors of this article like to thank all staff of endoscopy unit of Ayatollah Taleghani Hospital and Foodborne and Waterborne Diseases Research Center for their sincere help and assistance.
This study was part of a fellowship dissertation and financially supported by a grant from Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Compliance with ethical standards
This study was approved by the Ethics Committee of Shahid Beheshti University of Medical Sciences.
Conflict of interest
The authors declare that they have no conflict of interest.
- Alebouyeh M, Yadegar A, Farzi N, Miri M, Zojaji H, Gharibi S, Fazeli Z, Ebrahimi Daryani N, Asadzadeh Aghdaei H, Zali MR (2015) Impacts of H. pylori mixed-infection and heteroresistance on clinical outcomes. Gastroenterology and Hepatology from bed to bench 8(Suppl.1):S1–S5PubMedPubMedCentralGoogle Scholar
- Ayala G, Galván-Portillo M, Chihu L, Fierros G, Sánchez A, Carrillo B, Román A, López-Carrillo L, Silva-Sánchez J, Study Group J (2011) Resistance to antibiotics and characterization of Helicobacter pylori strains isolated from antrum and body from adults in Mexico. Microb Drug Resist 17(2):149–155CrossRefPubMedGoogle Scholar
- Boyanova L (2017) Amoxicillin/clarithromycin. Reactions 1646:34–38Google Scholar
- Finger SA, Velapatiño B, Kosek M, Santivañez L, Dailidiene D, Quino W, Balqui J, Herrera P, Berg DE, Gilman RH (2006) Effectiveness of enterobacterial repetitive intergenic consensus PCR and random amplified polymorphic DNA fingerprinting for Helicobacter pylori strain differentiation. Appl and Environ Microbiol 72(7):4713–4716CrossRefGoogle Scholar
- Kao CY, Sheu BS, Wu JJ (2016) Helicobacter pylori infection: an overview of bacterial virulence factors and pathogenesis. Biom J 39(1):14–23Google Scholar
- Malekzadeh R, Mohamadnejad M, Siavoshi F, Massarrat S (2004) Treatment of Helicobacter pylori in Iran: low efficacy of recommended western regimens. Arch Iranian Med 7(1):1–8Google Scholar
- Nishizawa T, Suzuki H (2014) Mechanisms of Helicobacter pylori antibiotic resistance and molecular testing. Front Mol Biosci 1Google Scholar
- Saberi-Firoozi M, Nejabat M (2006) Experiences with Helicobacter pylori treatment in Iran. Iran J Med Sci 31(4):181–185Google Scholar
- Selgrad M, Tammer I, Langner C, Bornschein J, Meißle J, Kandulski A, Varbanova M, Wex T, Schlüter D, Malfertheiner P (2014) Different antibiotic susceptibility between antrum and corpus of the stomach, a possible reason for treatment failure of Helicobacter pylori infection. World J Gastroenterol 20(43):16245–16251CrossRefPubMedPubMedCentralGoogle Scholar
- Wroblewski LE, Piazuelo MB, Chaturvedi R, Schumacher M, Aihara E, Feng R, Noto JM, Delgado A, Israel DA, Zavros Y, Montrose MH, Shroyer N, Correa P, Wilson KT, Peek RMJR (2014) Helicobacter pylori targets cancer-associated apical-junctional constituents in gastroids and gastric epithelial cells. Gut 64(5):720–730CrossRefPubMedPubMedCentralGoogle Scholar
- Zerbetto De Palma G, Mendiondo N, Wonaga A, Viola L, Ibarra D, Campitelli E, Salim N, Corti R, Goldman C, Catalano M (2017) Occurrence of mutations in the antimicrobial target genes related to levofloxacin, clarithromycin, and amoxicillin resistance in Helicobacter pylori isolates from Buenos Aires city. Microb Drug Resist 23(3):351–358CrossRefPubMedPubMedCentralGoogle Scholar