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Multicenter Study for the Frequency of 23S rRNA Point Mutations Associated with Clarithromycin Resistance in Helicobacter pylori in Korea

이종욱|김미나|이미경|이미애|채현석|성흥섭|강정옥|이혜경|심기남
대한임상미생물학회 (Korean Society of Clinical Microbiology)|2008.10|Annals of Clinical Microbiology|제11권 제2호|pp. 84-89

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KoreaHelicobacter pyloriClarithromycin resistance23S rRNA mutation

초록

배경: Clarithromycin (CLA)내성은 Helicobacter pylori 감염의 박멸 치료 실패의 중요한 원인이다. 본 연구에서는 한국에서 CLA 내성과 연관이 있는 23S rRNA 유전자 변이의 빈도와 유형을 분석하고자 하였다. 방법: 2008년 1월부터 2008년 3월까지 서울과 경기도 소재 5개 대학병원에 내원한 환자 353명으로부터 위생검조직을 채취하였다. H. pylori의 검출에서 3가지 방법(미호기성배양, 신속요소분해효소검사, Giemsa/silver 염색)중 한가지라도 양 성인 경우 H. pylori에 감염된 것으로 정의하였다. 모든 검체에 Seeplex ClaR-H. pylori PCR (Seegene Inc., Seoul, Korea)을 시행하여 H. pylori 감염여부, 23S rRNA의 야생형, A2143G 및 A2142G 변이형의 빈도를 조사하였다. 29균주에 대해서는 E-test (AB Biodisk, Solna, Sweden)나 CLSI (Clinical and Laboratory Standards Institute) 디스크확산법으로 CLA 감수성 검사 를 시행하였다. 결과: 176개의 Seeplex ClaR-H. pylori PCR양성 검체중 23S rRNA 변이가 38균주(A2143G 27균주, A2142G 11균주)에서 관찰되어 변이 빈도 21.6%를 보였다. 총 변이 빈도는 15.8%에서 31.3%로 병원에 따라 다양하였다. A2143G 변이 빈도는 5 병원에서 8.5%에서 25.0%로 다양하였다. CLA 감수성 검사에서 10균주가 내성을 나타내었는데 모두 A2143G 변이를 나타내었다. CLA 감수성 검사에서 감수성을 나타내었던 19균주중 3주가 변이형이었다. 결론: 한국에서 CLA 내성빈도는 21.6%이었으나 내성과 관련있는 23S rRNA 유전자 변이는 연구기관에 따라 빈도와 유 형이 다양하였다.

Abstract

Background: Clarithromycin resistance in Helicobacter pylori is a major cause of eradication therapy failure. The objective of this study was to determine the frequency and type of mutations in the 23S rRNA gene in Korea, which are associated with clarithromycin resistance. Methods: From January 2008 to March 2008, 353 gastric biopsy specimens were collected from five university hospitals in Seoul and Kyunggido. H. pylori infection was defined as showing a positive result in at least one of the following three tests: a microaerophilic culture, a CLO test, and a Giemsa/silver stain. The frequencies of A2143G, A2142G, and the wild type of 23S rRNA and the presence of H. pylori were determined by Seeplex ClaR-H. pylori PCR (Seegene Inc., Seoul, Korea). Twenty-nine culture isolates were tested for susceptibility to clarithromycin by E-test (AB Biodisk, Solna, Sweden) or the CLSI (Clinical and Laboratory Standards Institute) disk diffusion test. Results: From 176 H. pylori PCR-positive specimens, 23S rRNA gene mutations were detected in 38 isolates (21.6%), including 27 isolates of A2143G and 11 isolates of A2142G. Total mutation rates varied from 15.8% to 31.3% with the frequency of A2143G mutation alone varying from 8.5% to 25.0% among the five hospitals studied. There were 10 clarithromycin- resistant isolates found by susceptibility test and they were all positive for A2143G mutation. But, 3 of the 19 susceptible isolates were also positive for either A2143G or A2142G mutation. Conclusion: In Korea, the overall frequency of clarithromycin- resistant H. pylori was 21.6%; however, the type and frequency of the 23S rRNA mutations varied from hospital to hospital.

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