Korean Journal of Microbiology (미생물학회지)

The Microbiological Society of Korea (한국미생물학회)
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Relationship between Eradication of Helicobacter pylori Infection and Clarithromycin Resistance

Helicobacter pylori 감염의 치료와 Clarithromycin 내성간의 연관성

  • Sohn Seung Ghyu (Department of Biological Sciences, Myongji University) ;
  • Lee Jong Hwa (Research Center of Gastroenterology, College of Medicine, Dankook University) ;
  • Lee Jung Hun (Department of Biological Sciences, Myongji University) ;
  • Lee Sang Hee (Department of Biological Sciences, Myongji University)
  • 손승규 (명지대학교 자연과학대학 생명과학정보학부) ;
  • 이종화 (단국대학교 의과대학 소화기연구소) ;
  • 이정훈 (명지대학교 자연과학대학 생명과학정보학부) ;
  • 이상희 (명지대학교 자연과학대학 생명과학정보학부)
  • Published : 2005.09.01
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Abstract

H. pylori strains were isolated from antral biopsies taken during upper endoscopy in 114 dyspeptic patients with no previous therapy against H. pylori. Rapid urease test, PCR amplification of SSA and cagA gene for H. pylori detection, and Western blot for CagA expression detection were performed. H. pylori infected patients were treated with omeprazole, clarithromycin (a macrolide), and amoxicillin. At 6 weeks after the discontinuation of therapy, the bacterial eradication rate was determined by endoscopy. The resistance rate to clarithromycin and amoxicillin was $20.2\%$ and $0.0\%$, respectively. The clarithromycin resistance was mainly caused by the A2142G mutation in the 23S rRNA gene of H. pylori. MICs of clarithromycin for the A2142G mutant isolates were significantly higher than MICs for the A2143G mutant isolates. H. pylori eradication was obtained in all patients with clarithromycin-susceptible isolates but not in patients with clarithromycin-resistant isolates (P = 0.0001). These results did not appear to be biased by any differences in CagA expression. The resistance of H. pylori to clarithromycin included in the therapeutic regimens is the most important reason for treatment failure. H. pylori antimicrobial susceptibility testing of the gastric biopsy culture should be performed before choosing the first triple therapy in infected patients and the increase in prevalence of clarithromycin resistance in Korea was problematic.

본 연구를 수행하기 전에 H. pylori에 대한 어떠한 치료도 받지 않은 114명의 소화기 궤양 환자들을 내시경 검사를 하는 동안, 114개의 H. pylori 균주를 위 전정부로부터 분리하였다. H. pylori를 검출하기 위하여 rapid urease test, SSA와 cagA 유전자의 PCR증폭을 수행하였고, CagA 발현 검출을 위하여 Western blot을 수행하였다. H. pylori에 감염된 환자들은 omeprazole. clarithromycin (a macrolide), amoxicillin을 모두 사용하는데 3제 요법(triple therapy)으로 치료하였다. 치료가 중단되고 6주 후에 내시경 검사에서 세균 박멸률을 측정하였다. 내성률은 각각 clarithromycin이 $20.2\%$. amoxicillin이 $0.0\%$였다. Clarithromycin 내성은 H. pylori의 23S rRNA 유전자에 있는 A2142G돌연변이에 의한 것이 $87\%$이었다. A2142G돌연변이의 clarithromycin의 MIC값($32\~>256\;{\mu}g\ml$)은 A2143G돌연변이의 MIC값($4\~128\;{\mu}g/ml$)보다 더 높았다. Clarithromycin에 감수성을 가진 H. pylori는 박멸되었으나 clarithromycin내성을 가진 H. pylori는 박멸되지 않았다(P = 0.0001). 이러한 결과들은 CagA 발현에는 어떠한 영향도 받지 않았으며 H. pylori의 clarithromycin 내성은 치료 실패의 가장 중요한 이유임을 제시하였다. 우선적으로 실시되는 생검 배양에 대한 H. pylori의 항생제 감수성 시험은 감염된 환자들에 대한 3제 요법을 선택하기 이전에 필히 실시되어야 하며 국내에서 clarithromycin에 대한 1차 내성의 높은 빈도는 H. pylori의 감염증 치료에 심각한 문제점을 야기시켰다.

Keywords

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