Korean J Gastroenterol.  2013 May;61(5):252-258. 10.4166/kjg.2013.61.5.252.

Clarithromycin-resistant Helicobacter pylori Associated with 23S rRNA Point Mutations in Jeju Island

• Kim T
• Song HJ
• Shin SY
• Kim JH
• Na SY
• Boo SJ
• Choi EK
• Cho YK
• Kim HU
• Song BC

• KMID: 1501646
• DOI: http://doi.org/10.4166/kjg.2013.61.5.252

Abstract

BACKGROUND/AIMS
The point mutations in 23S rRNA gene accounts for the majority of the clarithromycin resistance of Helicobacter pylori. This study aimed to investigate the association between the clarithromycin-resistance of H. pylori and the failure of primary H. pylori eradication therapy in Jeju Island.
METHODS
Between April 2011 and October 2012, 6,937 patients underwent endoscopy, and H. pylori infection was evaluated in 2,287 patients (33.0%). Total of 110 patients with H. pylori infection were treated with proton pump inhibitor (PPI)-based triple therapy. The result of eradication was evaluated with urea breath test, histology and PCR which were conducted 4 weeks from the last dose of medicine.
RESULTS
The patients who had point mutations were 33 (26.0%). A2142G and A2143G mutations were observed in 10 patients (7.9%) and 23 patients (18.1%). Among 110 patients treated with PPI-based triple therapy, the success rate of the eradication therapy was 52.7% (58/110) and 70.7% (58/82) by intention-to-treat and per-protocol analysis, respectively. Fifteen of the 24 patients who failed the eradication therapy showed point mutations; 1 patient (4.2%) showed A2142G mutation and 14 patients (58.3%) showed A2143G mutation. Patients with A2143G mutation H. pylori showed higher failure rate of 87.5%. Patients with A2142G mutation H. pylori showed similar failure rate compared to those of the patients with wild type H. pylori.
CONCLUSIONS
In Jeju Island, the frequency of 23S rRNA point mutations is similar (26.0%) with other regions of Korea (15.8-31.3%). A2143G mutation is associated with the failure of H. pylori eradication.

Keyword

23S rRNA; Point mutation; Clarithromycin; Resistance; Helicobacter pylori

MeSH Terms

Adolescent
Adult
Aged
Aged, 80 and over
Anti-Bacterial Agents/*therapeutic use
Clarithromycin/*therapeutic use
DNA, Bacterial/analysis
Drug Resistance, Bacterial
Female
Gastroscopy
Helicobacter Infections/*drug therapy
Helicobacter pylori/drug effects/*genetics
Humans
Islands
Male
Middle Aged
Point Mutation
Polymerase Chain Reaction
Proton Pump Inhibitors/therapeutic use
RNA, Ribosomal, 23S/*genetics
Republic of Korea
Young Adult
Anti-Bacterial Agents
Clarithromycin
DNA, Bacterial
Proton Pump Inhibitors
RNA, Ribosomal, 23S

Figure

• 

  Fig. 1. Detection of point mutation at A2143G and A2142G in 23S rRNA gene by polymerase chain reaction products. M, marker; NC, negative control; PC1, PC2, clarithromycin resistance (PC1: A2143G, PC2: A2142G). Lane 28, A2143G mutation; lane 29, wild type; lane73, A2142G mutation.

• 

  Fig. 2. Results of Helicobacter pylori eradication with primary triple theraphy. PPI, proton pump inhibitor.

Reference

References

1. NIH consensus conference. Helicobacter pylori in peptic ulcer disease. NIH consensus development panel on Helicobacter pylori in peptic ulcer disease. JAMA. 1994; 272:65–69.

2. Blaser MJ. Hypothesis: the changing relationships of Helicobacter pylori and humans: implications for health and disease. J Infect Dis. 1999; 179:1523–1530.

3. Boyanova L, Mentis A, Gubina M, et al. The status of anti-microbial resistance of Helicobacter pylori in eastern Europe. Clin Microbiol Infect. 2002; 8:388–396.

4. Pounder RE, Ng D. The prevalence of Helicobacter pylori infection in different countries. Aliment Pharmacol Ther. 1995; 9(Suppl 2):33–39.

5. Yim JY, Kim N, Choi SH, et al. Seroprevalence of Helicobacter pylori in South Korea. Helicobacter. 2007; 12:333–340.

6. Kim JJ, Reddy R, Lee M, et al. Analysis of metronidazole, clarithromycin and tetracycline resistance of Helicobacter pylori isolates from Korea. J Antimicrob Chemother. 2001; 47:459–461.

7. Lee HK, Chae HS, Kang JO, et al. Multicenter study for the frequency of 23S rRNA Point mutations associated with clarithromycin resistance in Helicobacter pylori in Korea. Korean J Clin Microbiol. 2008; 11:84–89.

8. Houben MH, van de Beek D, Hensen EF, de Craen AJ, Rauws EA, Tytgat GN. A systematic review of Helicobacter pylori eradication therapy-the impact of antimicrobial resistance on eradication rates. Aliment Pharmacol Ther. 1999; 13:1047–1055.

9. Kim JY, Kim NY, Kim SJ, et al. Regional difference of antibiotic resistance of Helicobacter pylori strains in Korea. Korean J Gastroenterol. 2011; 57:221–229.

10. Woo HY, Park DI, Park H, et al. Dual-priming oligonucleotide-based multiplex PCR for the detection of Helicobacter pylori and determination of clarithromycin resistance with gastric biopsy specimens. Helicobacter. 2009; 14:22–28.

11. Kim JM, Kim JS, Jung HC, Kim N, Kim YJ, Song IS. Distribution of antibiotic MICs for Helicobacter pylori strains over a 16-year period in patients from Seoul, South Korea. Antimicrob Agents Chemother. 2004; 48:4843–4847.

12. Hwang TJ, Kim N, Kim HB, et al. Change in antibiotic resistance of Helicobacter pylori strains and the effect of A2143G point mutation of 23S rRNA on the eradication of H. pylori in a single center of Korea. J Clin Gastroenterol. 2010; 44:536–543.

13. Kim N, Kim JM, Kim CH, et al. Institutional difference of antibiotic resistance of Helicobacter pylori strains in Korea. J Clin Gastroenterol. 2006; 40:683–687.

14. Gerrits MM, van Vliet AH, Kuipers EJ, Kusters JG. Helicobacter pylori and antimicrobial resistance: molecular mechanisms and clinical implications. Lancet Infect Dis. 2006; 6:699–709.

15. Kim KS, Kang JO, Eun CS, Han DS, Choi TY. Mutations in the 23S rRNA gene of Helicobacter pylori associated with clarithromycin resistance. J Korean Med Sci. 2002; 17:599–603.

16. García-Arata MI, Baquero F, de Rafael L, et al. Mutations in 23S rRNA in Helicobacter pylori conferring resistance to erythromycin do not always confer resistance to clarithromycin. Antimicrob Agents Chemother. 1999; 43:374–376.

17. Versalovic J, Shortridge D, Kibler K, et al. Mutations in 23S rRNA are associated with clarithromycin resistance in Helicobacter pylori. Antimicrob Agents Chemother. 1996; 40:477–480.

18. De Francesco V, Margiotta M, Zullo A, et al. Clarithromycin-resistant genotypes and eradication of Helicobacter pylori. Ann Intern Med. 2006; 144:94–100.

19. Lee JH, Shin JH, Roe IH, et al. Impact of clarithromycin resistance on eradication of Helicobacter pylori in infected adults. Antimicrob Agents Chemother. 2005; 49:1600–1603.

20. Kim JM, Kim JS, Kim N, Kim SG, Jung HC, Song IS. Comparison of primary and secondary antimicrobial minimum inhibitory concentrations for Helicobacter pylori isolated from Korean patients. Int J Antimicrob Agents. 2006; 28:6–13.

21. Sung H, Chung HJ, Kim MN, Lee GH. Clinical usefulness of anti-microbial susceptibility test for Helicobacter pylori. Korean J Lab Med. 2006; 26:179–184.

22. Kim HU, Song HJ, Choi EK, Cho YK, Song BC. The eradication rate of Helicobacter pylori using PPI-based triple therapy in Jeju Island. Korean J Helicobacter Up Gastrointest Res. 2009; 9:26–30.

23. Cho AR, Lee MK. A comparison analysis on the diagnosis of Helicobacter pylori infection and the detection of clarithromycin resistance according to biopsy sites. Korean J Lab Med. 2010; 30:381–387.