Change of Clostridium difficile Colitis during Recent 10 Years in Korea

최근 10년간 Clostridium difficile 대장염의 임상 양상 변화

Lee, Yun-Jeong;Choe, Myeong-Gyu;Im, Cheol-Hyeon;Jeong, Ung-Ryong;Jo, Hyeon-Seon;Seong, Hye-Yeong;Nam, Gwan-U;Jang, Jae-Hyeok;Jo, Yu-Gyeong;Park, Jae-Myeong;Kim, Sang-U;Jeong, In-Sik
이윤정;최명규;임철현;정웅룡;조현선;성혜영;남관우;장재혁;조유경;박재명;김상우;정인식

  • Published : 20100000

Abstract

Background/Aims: Our clinical experience and recent published literatures suggest that Clostridium difficile colitis (CDC) has become more common and potentially more pathogenic in recent years. The aim of study was to evaluate changes in the epidemiological features of CDC in hospitalized patients in Korea. Methods: We retrospectively reviewed all patients of CDC diagnosed at Kangnam St. Mary Hospital from 1998 to 2007. CDC was defined as having a positive C. difficile cytotoxicity assay, or endoscopic or pathologic evidence of CDC. Results: A total of 189 cases (male 73, female 116, mean age 63.3 years) of CDC were diagnosed during the study period. The prevalence of CDC increased from 1.9/10,000 patient admissions in 1998-1999 to 8.82/10,000 patient admissions in 2006-2007. One hundred sixty three indication for cases (86.2%) of patients identified a prior use of antibiotics in the 2 months preceding diagnosis. The most common antibiotic use was prophylactic use during perioperational period (33.3%) followed by pneumonia (23.3%). The overall response rate to initial antibiotics was 82.7%. One hundred seventy two (91%) patients were initially treated with metronidazole. The response rate was 84.3%. All patients with initial failure to metronidazole were successfully treated by vancomycin. The response rate of vancomycin as first treatment was 80%. Three deaths were associated with CDC despite the use of combinationof metronidazole and vancomycin. Conclusions: The prevalence of CDC in hospitalized patients in Korea significantly increased from 1998 to 2007.

목적: 최근 수년간의 임상 경험과 최근 발표들은 Clostridium difficile 대장염(CDC)이 더욱 흔해지고 병인성이 강해짐을 시사한다. 이 연구의 목적은 한국에서 입원 환자의 CDC의 역학적인 특징 변화를 조사하는 것이다. 대상 및 방법: 1998년 1월부터 2007년 12월까지 강남성모병원에서 CDC로 진단받은 환자를 전향 조사했다. Clostridium difficile 세포독성검사에서 양성이거나 내시경 또는 병리 증거가 존재할 경우 CDC로 정의했다. 결과: 연구 기간 동안 총 189명(남자 73명, 여자 116명)이 CDC로 진단되었다. 평균 연령은 63.3세였다. 65세 초과 환자는 103명(54.4%)이었다. 1998년부터 2007년까지 CDC의 유병률은 유의하게 증가했다. CDC의 유병률은 1997-1998년 입원환자 10,000명당 1.9명에서 2006-2007년 입원환자 10,000명당 8.82명으로 증가했다. 163건(86.2%)에서 진단 2개월 이내에 항생제 사용을 확인했다. 사용한 항생제는 평균 2.1종류였고 항생제 사용 기간은 평균 18.8일(1-240일)이었다. Cephalosporin이 가장 많은 131명(80.4%)에서 투여되었고, 다음으로 aminoglycoside는 85명(52.1%), fluoroquinolone은 24명(14.7%), macrolide는 20명(12.3%) 순으로 사용되었다. 가장 많은 항생제 사용 원인으로 수술 전후 예방적 투여(33.3%)와 폐렴(23.3%)이었다. CDC에 대한 초기 항생제 치료 반응률은 82.7% (153/ 184)였다. Metronidazole에 대한 반응률은 84.3% (145/172)였다. Metronidazole 초치료에 실패한 모든 환자는 vancomycin으로 성공적으로 치료되었다. Vancomycin으로 1차 치료 시 반응률은 80% (4/5)였다. 3명의 환자가 metronidazole과 vancomycin 복합 치료에도 불구하고 CDC와 관련하여 사망했다. 결론: 1998년부터 2007년까지 한국에서 입원 환자의 CDC 유병률이 유의하게 증가했다.

Keywords

References

  1. Larson HE, Price AB, Honour P, Borriello SP. Clostridium difficile and the aetiology of pseudomembranous colitis. 1978;1:1063-1066
  2. Loo VG, Poirier L, Miller MA, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 2005;353:2442-2249 https://doi.org/10.1056/NEJMoa051639
  3. P$\acute{e}$pin J, Valiquette L, Cossette B. Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec. CMAJ 2005;173:1037-1042 https://doi.org/10.1503/cmaj.050978
  4. P$\acute{e}$pin J, Valiquette L, Alary ME, et al. Clostridium difficileassociated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. CMAJ 2004;171:466-472 https://doi.org/10.1503/cmaj.1041104
  5. Lim PS, Yun HD, Yim KW, Song IS, Choi KW, Kim CY. A clinical study on pseudomembranous colitis. Korean J Gastrointest Endosc 1987;7:13-17
  6. Chung MH, Hyun MS, Lee HJ, Chung MK, Shim MC, Lee TS. A clinical study of pseudomembranous enterocolitis. Korean J Med 1988;34:673-680
  7. Lee CR, Lee JK, Cho YS, Yoo HM, Kim WH, Lee KW. A clinical investigation of Clostridium difficile-associated disease. Korean J Gastroenterol 1999;33:338-347
  8. Kim DS, Kim NS, Lee SH. Determination of defined daily dose of medicines using nominal group technique and analysis of antibiotics use in national insurance claim data: focused on antibiotics without DDD of WHO. Korean J Clin Pharm 2007;17:19-32
  9. Hirschborn LR, Trnka Y, Onderdonk A, Lee ML, Platt R. Epidemiology of community-aquired Clostridium difficile- associated diarrhea. J Infect Dis 1994;169:127-133
  10. Frost F, Hurley JS, Petersen HV, Casciano RN. Estimated incidence of Clostridium difficile infection. Emerg Infect Dis 1999;5:303-304 https://doi.org/10.3201/eid0502.990224
  11. Karlström O, Fryklund B, Tullus K, Burman LG. A prospective nationwide study of C. difficile-associated diarrhea in Sweden. The Swedish C. difficile study Group. Clin Infect Dis 1998;26:141-145 https://doi.org/10.1086/516277
  12. Zilberberg MD, Shorr AF, Kollef MH. Increase in adult Clostridium difficile-related hospitalizations and case-fatality rate, United States, 2000-2005. Emerg Infect Dis 2008;14:929-931 https://doi.org/10.3201/eid1406.071447
  13. Barbut F, Gariazzo B, Bonn$\acute{e}$ L, et al. Clinical features of Clostridium difficile-associated infections and molecular characterization of strains: results of a retrospective study, 2000-2004. Infect Control Hosp Epidemiol 2007;28:131-139 https://doi.org/10.1086/511794
  14. Hubert B, Loo VG, Bourgault AM, et al. Portrait of the geographic dissemination of the Clostridium difficile North American pulsed-field type 1 strain and the epidemiology of C. difficile-associated disease in Québec. Clin Infect Dis 2007;44:238-244 https://doi.org/10.1086/510391
  15. Warny M, Pepin J, Fang A, et al. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 2005;366:1079-1084 https://doi.org/10.1016/S0140-6736(05)67420-X
  16. Tae CH, Jung SA, Song HJ, et al. The first case of antibiotic-associated colitis by Clostridium difficile PCR ribotype 027 in Korea. J Korean Med Sci 2009;24:520-524 https://doi.org/10.3346/jkms.2009.24.3.520
  17. Shin BM, Kuak EY, Yoo HM, et al. Multicentre study of the prevalence of toxigenic Clostridium difficile in Korea: results of a retrospective study 2000-2005. J Med Microbiol 2008;57:697-701 https://doi.org/10.1099/jmm.0.47771-0
  18. Abrahamian FM, Talan DA, Moran GJ, Pinner R. Update on emerging infections from the Centers for Disease Control and Prevention. Severe Clostridium difficile-associated disease in populations previously at low risk-four states, 2005. Ann Emerg Med 2006;48:55-59
  19. Rodriguez-Palacios A, Stämpfli HR, Duffield T, et al. Clostridium difficile PCR ribotypes in calves, Canada. Emerg Infect Dis 2006;12:1730-1736
  20. Kazakova SV, Ware K, Baughman B, et al. A hospital outbreak of diarrhea due to an emerging epidemic strain of Clostridium difficile. Arch Intern Med 2006;166:2518-2524 https://doi.org/10.1001/archinte.166.22.2518
  21. Muto CA, Pokrywka M, Shutt K, et al. A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use. Infect Control Hosp Epidemiol 2005;26:273-280 https://doi.org/10.1086/502539
  22. Aseeri M, Schroeder T, Kramer J, Zackula R. Gastric acid suppression by proton pump inhibitors as a risk factor for Clostridium difficile-associated diarrhea in hospitalized patients. Am J Gastroenterol 2008;103:2308-2013 https://doi.org/10.1111/j.1572-0241.2008.01975.x
  23. Monaghan T, Boswell T, Mahida YR. Recent advances in Clostridium difficile-associated disease. Gut 2008;57:850-860
  24. Gerding DN, Muto CA, Owens RC Jr. Treatment of Clostridium difficile infection. Clin Infect Dis 2008;46(suppl 1):S32-S42 https://doi.org/10.1086/521860
  25. P$\acute{e}$pin J, Alary ME, Valiquette L, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis 2005;40:1591-1597 https://doi.org/10.1086/430315