A Domestic Outbreak of Bacterial Dysentery Caused by Extended-Spectrum β-Lactamase(ESBL)-producing Shigella sonnei

집단 발생한 Extended-spectrum β-lactamase(ESBL) 생산 Shigella sonnei 감염에 의한 세균성 이질에 관한 연구

  • Lim, Hyun Taek (Department of Pediatrics College of Medicine, Konkuk University) ;
  • Lee, So Hee (Department of Pediatrics College of Medicine, Konkuk University) ;
  • Lee, Jung Hwa (Department of Pediatrics College of Medicine, Konkuk University) ;
  • Kim, Jeong Eun (Department of Pediatrics College of Medicine, Konkuk University) ;
  • Kim, Kyo Sun (Department of Pediatrics College of Medicine, Konkuk University) ;
  • Jeong, Eun Ju (Department of Microbiology College of Medicine, Konkuk University) ;
  • Lee, Seung Hyun (Department of Microbiology College of Medicine, Konkuk University) ;
  • Kang, Chang Gyu (Local Corporation Chungju Medical Center) ;
  • Hong, Seong Jin (Department of Pediatrics College of Medicine, Konkuk University)
  • 임현택 (건국대학교 의과대학 소아과학교실) ;
  • 이소희 (건국대학교 의과대학 소아과학교실) ;
  • 이정화 (건국대학교 의과대학 소아과학교실) ;
  • 김정은 (건국대학교 의과대학 소아과학교실) ;
  • 김교순 (건국대학교 의과대학 소아과학교실) ;
  • 정은주 (건국대학교 의과대학 미생물학교실) ;
  • 이승현 (건국대학교 의과대학 미생물학교실) ;
  • 강창규 (지방공사 충주의료원) ;
  • 홍성진 (건국대학교 의과대학 소아과학교실)
  • Received : 2005.06.20
  • Accepted : 2005.08.05
  • Published : 2005.10.15

Abstract

Purpose : An outbreak of ESBL-producing Shigella sonnei enteritis was unprecedented not only in Korea but throughout the world in the past. We intended to devise a management guideline for ESBL-producing shigellosis based on analysis of clinical manifestations and response to therapy. Methods : We analyzed 103 patients who were admitted to the hospital with acute GI symptoms and were shown positive result for S. sonnei on stool culture. We performed sensitivity test to the antibiotics and DNA sequencing of ESBL gene in the isolated S. sonnei colonies. In addition, we retrospectively analyzed their clinical characteristics, laboratory results, and clinical and microbiological responses to the antibiotics. Results : Among the clinical manifestations, fever was the most frequent(96.1%), followed by diarrhea(93.2%), abdominal pain(76.7%), headache(71.8%), vomiting(65.0%), and nausea(41.7%). The fever was sustained for average of 2.0 days and diarrhea for 3.9 days. Watery diarrhea was the most common(69%) followed by mucoid(26%), and bloody stool(5%). On peripheral blood smear, leukocytosis was noted in 53.4% of patients, and 78.6% of patients tested positive for serum CRP response. On stool direct smear, 11.7% of patients showed more than 50 WBCs/HPF, and 9.7% of patients between 5 to 20 WBCs/HPF. Stool occult blood was positive in 71% of patients. Production of CTX-M-14 type ESBL was reported for all S. sonnei strains isolated from this outbreak. Microbiological eradication rates to various antibiotics were as follows : 100%(9/9) to ciprofloxacin, 100% 5/5) to azithromycin, 6.9%(5/72) to cefdinir, 0%(0/8) to ceftriaxone, 12.5%(1/8) to ceftizoxime, 0%(0/ 8) to TMP/SMX, 42.9%(3/7) to ampicillin/sulbactam, 20%(1/5) to amoxicillin/clavulanic acid, and 68.8 %(11/16) to imipenem/cilastatin. Conclusion : It is presumed that azithromycin can be an attractive option for the treatment of ESBL-producing S. sonnei enteritis in pediatric population, given its cost-effectiveness and safety. Although ciprofloxacin is another cost-effective agent, its use in pediatric population may be a bit too premature.

목 적 : ESBL 생산 S. sonnei에 의한 장염의 대규모 발생은 과거 국내는 물론 세계에서도 유래를 찾아볼 수 없었다. 저자들은 집단 발생한 ESBL 생산 S. sonnei에 의한 장염 환자의 임상적 특징과 치료에 대한 반응 등을 분석하여 ESBL 생산 S. sonnei 감염증에 대한 치료 지침을 마련하는데 도움이 되고자 한다. 방 법 : 연구 대상은 2004년 11월 충주 ${\bigcirc}{\bigcirc}$초등학교를 중심으로 집단 발생한 급성 장염 환자 중 분변 배양 검사상 S. sonnei가 검출되어 치료받은 환자 103명을 대상으로 하였다. 환자에서 분리된 S. sonnei에 대해 항생제 감수성 검사와 DNA 염기 서열 검사를 시행하였고, 환자들의 임상적 특징과 검사 소견, 그리고 항생제에 대한 반응 등을 후향적으로 분석하였다. 결 과 : 임상 증상은 발열 96.1%, 설사 93.2%, 복통 76.7%, 두통 71.8%, 구토 65.0%, 그리고 구역 41.7% 순으로 나타났다. 발열은 평균 2.0일간 지속되었고, 설사는 평균 3.9일간 지속되었다. 설사의 양상은 수양성 설사는 69%, 점액성 설사는 26%, 그리고 혈변은 5%에서 관찰되었다. 말초 혈액 검사에서 백혈구 증다증을 보이는 경우는 53.4%이었고, 혈청 검사에서 CRP 양성을 보이는 경우는 78.6%이었다. 대변 직접 도말 검사에서 백혈구가 고배율 당 50개 이상인 경우가 11.7%, 그리고 5-20개인 경우 9.7%이었다. 대변 잠혈 반응은 71%에서 양성이었다. 본 유행에서 분리된 ESBL의 유형은 염기 서열을 분석한 결과 CTX-M-14 유형으로 밝혀졌다. 항생제 투여에 대한 미생물학적 치료 결과는 ciprofloxacin 투여자 중 100%(9/9), azithromycin 투여자 중 100%(5/5), cefdinir 투여자 중 6.9%(5/72), ceftriaxone 투여자 중 0%(0/8), ceftizoxime 투여자 중 12.5%(1/8), TMP/SMX 투여자 중 0%(0/8), ampicillin/sulbactam 투여자 중 42.9%(3/7), amoxicillin/clavulanic acid 투여자 중 20%(1/5), 그리고 imipenem/cilastatin 투여자 중 68.8%(11/16)에서 추적 검사상 음전 되었다. 결 론 : 소아에서 발생한 ESBL 생산 S. sonnei에 의한 세균성 이질에 대한 항생제 선택에서 비용-효과 면이나 안전성 면에서 azithromycin이 매력적인 일차 선택약일 수 있을 것으로 사료된다. Ciprofloxacin은 비용-효과 면에서는 우수한 약제일 수는 있으나 소아에서의 사용은 아직 이르다고 생각된다.

Keywords

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