1887

Journal of Medical Microbiology logo

Volume 68, Issue 4

Editor's Choice Comparison of new and classical point mutations associated with clarithromycin resistance in strains isolated from dyspeptic patients and their effects on phenotypic clarithromycin resistance Free

Abstract

We aimed to investigate the presence of three recently identified point mutations (A2115G, G2141A and A2144T) of the 23 S rRNA gene and compare them with the three most frequently encountered point mutations (A2142G, A2142C and A2143G) in strains in Turkey.

A total of 63 patients (mean 47.08±12.27) were included. The E-test method (for clarithromycin) was used for the clarithromycin antimicrobial susceptibility test of isolated strains. Real-time PCR was used to detect the point mutations.

A total of 24 out of 63 strains (38.1%) were detected as clarithromycin resistant (>0.5 mg l ). The new A2115G (:6, 25%), A2144T (:7, 29.1%) and G2141A, 8 (:8, 33.3%) mutations and the classical A2142G (:8, 33.3%) and A2143G (:11, 45.8%) point mutations were detected in the 24 clarithromycin-resistant strains. The A2144T point mutation had the highest median MIC value (3 mg l ) amongst the new mutations, but the classical mutations (A2142G and A2143G) had the highest median MIC values (256 mg l ) overall. The presence of the A2115G (OR:31.66), A2144T (OR:36.92) or G2141A (OR:28.16) mutations increased the likelihood of clarithromycin resistance in strains by 31.66-, 36.92- and 28.16-fold (ORs), respectively, according to the binary logistic regression analysis.

. We concluded that classical mutations of the 23 S rRNA gene resulted in higher clarithromycin MIC values than new mutations. These new point mutations caused moderate elevations in the MIC values of clarithromycin-resistant strains.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): A2115G, A2144T and G2141A , clarithromycin , Helicobacter pylori and point mutations
© 2019 The Authors
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000944
2019-04-01
2024-09-14
Loading full text...

Full text loading...

/deliver/fulltext/jmm/68/4/566.html?itemId=/content/journal/jmm/10.1099/jmm.0.000944&mimeType=html&fmt=ahah

References

  1. Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology 2017; 153:420–429 [View Article]
     [Google Scholar]
  2. Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 1991; 325:1127–1131 PMID: 1891020 [View Article]
     [Google Scholar]
  3. Shinzaki S, Fujii T, Bamba S, Ogawa M, Kobayashi T et al. Seven days triple therapy for eradication of Helicobacter pylori does not alter the disease activity of patients with inflammatory bowel disease. Intest Res 2018; 16:609–618 [View Article]
     [Google Scholar]
  4. Rimbara E, Fischbach LA, Graham DY. Optimal therapy for Helicobacter pylori infections. Nat Rev Gastroenterol Hepatol 2011; 8:79–88 [View Article]
     [Google Scholar]
  5. Graham DY, Fischbach L. Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut 2010; 59:1143–1153 [View Article]
     [Google Scholar]
  6. Hultén K, Gibreel A, Sköld O, Engstrand L. Macrolide resistance in Helicobacter pylori: mechanism and stability in strains from clarithromycin-treated patients. Antimicrob Agents Chemother 1997; 41:2550–2553 PMCID: PMC164161 [View Article]
     [Google Scholar]
  7. Ahmad N, Zakaria WR, Abdullah SA, Mohamed R. Characterization of clarithromycin resistance in Malaysian isolates of Helicobacter pylori . World J Gastroenterol 2009; 15:3161 [View Article]
     [Google Scholar]
  8. Toracchio S, Aceto GM, Mariani-Costantini R, Battista P, Marzio L. Identification of a novel mutation affecting domain V of the 23S rRNA gene in Helicobacter pylori . Helicobacter 2004; 9:396–399 [View Article]
     [Google Scholar]
  9. De Francesco V, Zullo A, Hassan C, Giorgio F, Rosania R et al. Mechanisms of Helicobacter pylori antibiotic resistance: an updated appraisal. World J Gastrointest Pathophysiol 2011; 2:35–41 [View Article]
     [Google Scholar]
  10. Fontana C, Favaro M, Minelli S, Criscuolo AA, Pietroiusti A et al. New site of modification of 23S rRNA associated with clarithromycin resistance of Helicobacter pylori clinical isolates. Antimicrob Agents Chemother 2002; 46:3765–3769 [View Article]
     [Google Scholar]
  11. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) Breakpoint tables for interpretation of MICs and zone diameters (version 6.0); 2013 http://www.eucast.org/clinical_breakpoints/ 6 August, 2018
  12. Tharmalingam N, Port J, Castillo D, Mylonakis E. Repurposing the anthelmintic drug niclosamide to combat Helicobacter pylori . Sci Rep 2018; 8:3701 PMID: 29487357 [View Article]
     [Google Scholar]
  13. De Francesco V, Zullo A, Giorgio F, Saracino I, Zaccaro C et al. Change of point mutations in Helicobacter pylori rRNA associated with clarithromycin resistance in Italy. J Med Microbiol 2014; 63:453–457 [View Article]
     [Google Scholar]
  14. Ménard A, Santos A, Mégraud F, Oleastro M. PCR-restriction fragment length polymorphism can also detect point mutation A2142C in the 23S rRNA gene, associated with Helicobacter pylori resistance to clarithromycin. Antimicrob Agents Chemother 2002; 46:1156–1157 [View Article]
     [Google Scholar]
  15. Oleastro M, Ménard A, Santos A, Lamouliatte H, Monteiro L et al. Real-time PCR assay for rapid and accurate detection of point mutations conferring resistance to clarithromycin in Helicobacter pylori . J Clin Microbiol 2003; 41:397–402 [View Article]
     [Google Scholar]
  16. Agudo S, Pérez-Pérez G, Alarcón T, López-Brea M. High prevalence of clarithromycin-resistant Helicobacter pylori strains and risk factors associated with resistance in Madrid, Spain. J Clin Microbiol 2010; 48:3703–3707 [View Article]
     [Google Scholar]
  17. Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ et al. European Helicobacter and microbiota study group and consensus panel. Management of Helicobacter pylori infection-the Maastricht V/Florence consensus report. Gut 2017; 66:6–30
     [Google Scholar]
  18. Thung I, Aramin H, Vavinskaya V, Gupta S, Park JY et al. Review article: the global emergence of Helicobacter pylori antibiotic resistance. Aliment Pharmacol Ther 2016; 43:514–533 [View Article]
     [Google Scholar]
  19. Georgopoulos SD, Xirouchakis E, Martinez-Gonzalez B, Sgouras DN, Spiliadi C et al. Clinical evaluation of a ten-day regimen with esomeprazole, metronidazole, amoxicillin, and clarithromycin for the eradication of Helicobacter pylori in a high clarithromycin resistance area. Helicobacter 2013; 18:459–467 [View Article]
     [Google Scholar]
  20. Boyanova L, Mitov I. Geographic map and evolution of primary Helicobacter pylori resistance to antibacterial agents. Expert Rev Anti Infect Ther 2010; 8:59–70 [View Article]
     [Google Scholar]
  21. Megraud F, Coenen S, Versporten A, Kist M, Lopez-Brea M et al. Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut 2013; 62:34–42 [View Article]
     [Google Scholar]
  22. Larsen AL, Ragnhildstveit E, Moayeri B, Eliassen L, Melby KK. Resistance rates of metronidazole and other antibacterials in Helicobacter pylori from previously untreated patients in Norway. APMIS 2013; 121:353–358 [View Article]
     [Google Scholar]
  23. Caliskan R, Tokman HB, Erzin Y, Saribas S, Yuksel P et al. Antimicrobial resistance of Helicobacter pylori strains to five antibiotics, including levofloxacin, in Northwestern Turkey. Rev Soc Bras Med Trop 2015; 48:278–284 [View Article]
     [Google Scholar]
  24. Monno R, Giorgio F, Carmine P, Soleo L, Cinquepalmi V et al. Helicobacter pylori clarithromycin resistance detected by Etest and TaqMan real-time polymerase chain reaction: a comparative study. APMIS 2012; 120:712–717 [View Article]
     [Google Scholar]
  25. De Francesco V, Zullo A, Ierardi E, Vaira D. Minimal inhibitory concentration (MIC) values and different point mutations in the 23S rRNA gene for clarithromycin resistance in Helicobacter pylori . Dig Liver Dis 2009; 41:610–611 [View Article]
     [Google Scholar]
  26. Binyamin D, Pastukh N, On A, Paritsky M, Peretz A. Phenotypic and genotypic correlation as expressed in Helicobacter pylori resistance to clarithromycin and fluoroquinolones. Gut Pathog 2017; 9:1 [View Article]
     [Google Scholar]
  27. van Doorn LJ, Glupczynski Y, Kusters JG, Megraud F, Midolo P et al. Accurate prediction of macrolide resistance in Helicobacter pylori by a PCR line probe assay for detection of mutations in the 23S rRNA gene: multicenter validation study. Antimicrob Agents Chemother 2001; 45:1500–1504 [View Article]
     [Google Scholar]
  28. Owen RJ. Molecular testing for antibiotic resistance in Helicobacter pylori . Gut 2002; 50:285–289 [View Article]
     [Google Scholar]
  29. Mégraud F. H pylori antibiotic resistance: prevalence, importance, and advances in testing. Gut 2004; 53:1374–1384 [View Article]
     [Google Scholar]
/content/journal/jmm/10.1099/jmm.0.000944
Loading
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. 68, 566 (2019); https://doi.org/10.1099/jmm.0.000944
/content/journal/jmm/10.1099/jmm.0.000944
/content/journal/jmm/10.1099/jmm.0.000944
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error