원저 Lab Med Online Vol. 7, No. 2: 73-78, April 임상미생물학 Clostridium difficile 감염증진단을위한검사법의비교평가 Comparison an

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D., Wonmok Lee, M.D., Jung-Sook Ha, M.D., Nam-Hee Ryoo, M.D., Dong-Seok Jeon, M.D., Jae-Ryong Kim, M.D. 계명대학교의과대학진단검사의학교실 Departments of Laboratory Medicine, Keimyung University School of Medicine,

In patients who have a history of antibiotic use and diarrhea, the presence of the C. difficile toxin should be confirmed to diagnose C. difficile infection (CDI).

1 원저 Lab Med Online Vol. 7, No. 2: 73-78, April 2017 임상미생물학 Clostridium difficile 감염증진단을위한검사법의비교평가 Comparison and Evaluation of Diagnostic Assays for Clostridium difficile Infection 김경보 김도훈 이원목 하정숙 류남희 전동석 김재룡 Kyoung-Bo Kim, M.D., Do Hoon Kim, M.D., Wonmok Lee, M.D., Jung-Sook Ha, M.D., Nam-Hee Ryoo, M.D., Dong-Seok Jeon, M.D., Jae-Ryong Kim, M.D. 계명대학교의과대학진단검사의학교실 Departments of Laboratory Medicine, Keimyung University School of Medicine, Daegu, Korea Background: Clostridium difficile is a leading causative microorganism of pseudomembranous colitis (PMC) and antibiotic-associated diarrhea. In patients who have a history of antibiotic use and diarrhea, the presence of the C. difficile toxin should be confirmed to diagnose C. difficile infection (CDI). In this study, the results of three assays for CDI, which were performed on 1,363 clinical stool samples at a tertiary hospital, were analyzed to evaluate the performance and usefulness of these assays for diagnosis of CDI. Methods: The results of the VIDAS C. difficile Toxin A&B Immunoassay (biomérieux SA, France), Xpert C. difficile Real-Time PCR Assay (Cepheid, USA), and ChromID C. difficile Agar (biomérieux SA, France) culture were analyzed retrospectively. Cases were defined as CDI according to the positive Xpert assay or the positive VIDAS assay and/or culture in the presence of PMC findings after radiological imaging or endoscopic procedures. Results: A total of 1,027 samples (75.8%) tested negative in all three assays, 101 samples (7.4%) tested positive in all three assays, and overall agreement among them was 82.7%. In this study, 291 cases (21.3%) were diagnosed as CDI. Sensitivity and specificity of the VIDAS assay were 38.8% and 99.3%, and those of ChromID culture were 71.5% and 96.5%, respectively. The Xpert assay showed good sensitivity (98.6%, 287/291), whereas the VIDAS assay and ChromID culture showed low sensitivities. Conclusions: These results suggest that rapid molecular diagnostic assays, such as the Xpert assay, are promising candidates for an initial diagnostic test for CDI. Key Words: Clostridium difficile, Molecular diagnostic testing, Diagnostic test, Xpert 서론 Clostridium difficile 은무산소성그람양성막대균으로항균제 사용후발생하는위막성대장염 (pseudomembranous colitis, PMC) 의주요원인균이며, 원내에서발생하는항생제관련설사의원인 균중하나이다 [1]. C. difficile 감염증 (C. difficile infection, CDI) 은 C. difficile 이생성하는독소 A (enterotoxin) 와독소 B (cytotoxin) Corresponding author: Nam-Hee Ryoo Department of Laboratory Medicine, Keimyung University School of Medicine, 56 Dalseong-ro, Jung-gu, Daegu 41931, Korea Tel: , Fax: , nhryoo@naver.com Received: June 23, 2016 Revision received: September 13, 2016 Accepted: September 26, 2016 This article is available from , Laboratory Medicine Online This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 중주로독소 B에의해발생하며, 증상은단순설사부터패혈증까지다양하게나타날수있다. CDI의진단을위해서는설사혹은장폐색증상을보이는환자를대상으로검사실에서독소를생성하는 C. difficile의존재를증명하거나, 영상학적검사혹은내시경검사를통해 PMC의특징적인소견을확인해야한다 [2]. 이중실험실적검사법으로는독소를검출하는면역검사법과선택배지를이용한 C. difficile 배양법이예전부터이용되었으며, 독소배양법 (toxigenic culture) 이표준검사법으로사용되어왔다 [3-7]. 최근에는독소생성유전자를직접검출하는분자진단검사법이상용화되어진단에이용되고있다 [3-5, 7-10]. 기존연구들에따르면 C. difficile의공통항원인글루탐산탈수소효소 (glutamate dehydrogenase, GDH) 를검출하는면역학적검사는민감도는높으나독소생성유무를추가로확인해야하는단점이있으며, 독소면역검사법의경우다른검사법들에비해민감도가낮은단점을가지고있다. 한편배양법은양성이나오더라도단독으로는 C. difficile의독소생성유무를확인할수없어추가검사가필요하다는제한점을가지고있다 [11-13]. 또한표준검사법 eissn

2 인독소배양법은특수한배양조건과비교적긴검사시간으로인해일반검사실들에서실제시행되기어렵다. 이러한이유로 CDI 관련학회및문헌들에서는 CDI 진단을위해선별검사와확진검사로나뉘어진 2, 3단계의검사알고리즘을제시하였다 [2, 4, 14, 15]. 하지만이러한알고리즘들은단일검사에비해최종판정까지소요되는시간이길어지고 [4, 15] 면역검사법의경우 ribotype에따라민감도가낮아지는등실제임상에적용하기에제한점이많았다 [5]. 이러한기존검사법들과알고리즘의한계점이존재하는가운데, 최근분자진단검사법의자동화와더불어다양한 CDI 검사법들이개발됨에따라새로운진단알고리즘에대한많은연구들이이루어지고있다 [11, 15-17]. 이에본연구는한대학병원검사실에서 CDI 진단을위해의뢰된대변검체로시행된면역검사법, 배양법및분자진단검사법의결과를분석함으로써, CDI 진단검사법들의성능을비교평가하고기존진단알고리즘의개선점을모색하고자하였다. 재료및방법 1. 대상 한대학병원에서 2014년 11월 7일부터 2016년 3월 7일까지 CDI 검사를위해검사실로의뢰된대변검체 1,384개를대상으로하였다. 본검사실에서는기존에시행하던면역검사법인 VIDAS C. difficile Toxin A&B (biomérieux SA, Marcy l Etoile, France) 검사및 ChromID C. difficile agar (biomérieux SA) 를이용한배양검사와최근도입된분자진단검사법인 Xpert C. difficile assay (Cepheid, Sunnyvale, CA, USA) 를비교평가하기위해, 검사실로의뢰된검체에대해세가지검사를모두시행하였다. 가능한검사실도착즉시검사를시행하였으며, 바로검사를시행할수없는경우 4 C 에서보관후최대 72시간이내에모든검사를시행하였다. 전체검체중동일환자에서같은날의뢰된중복검체 21건은제외하였으며, 최종 1,363개검체의결과를후향적으로분석하였다. 2. 방법 1) VIDAS C. difficile Toxin A&B assay VIDAS C. difficile Toxin A&B assay는 C. difficile 독소 A와독소 B를효소결합형광분석법 (enzyme-linked fluorescent assay) 으로검출하는면역검사법이다. 모든검사과정은제조사의지침에따랐으며, 대변검체 200 μl를원심분리튜브에분주하고희석액 1,000 μl와잘혼합한후 12,000 g에서 5분간원심분리하였다. 이후상층액 300 μl를이용하여 mini VIDAS (biomérieux SA) 장비로 CD Toxin A&B를측정하였다. 결과는측정된형광강도에따른결과치가 0.37 이상인경우양성, 0.37 미만인경우음성으로판정하였다. 2) Xpert C. difficile assay Xpert C. difficile assay는실시간중합효소반응원리를이용해 tcdb, cdt 유전자의유무, 그리고 tcdc 유전자의돌연변이유무를검출하는분자진단검사법이다. 전검사과정은제조사의지침에따랐으며, 검체를면봉으로채취하여시약튜브에넣고혼합하여카트리지통에옮긴후 GeneXpert Dx (Cepheid) 장비를이용해검사를시행하였다. 결과는 tcdb, cdt 유전자및 tcdcδ117을표적으로하는세개의 probe와하나의양성대조군 probe의 Ct 값을확인하여독소생성 C. difficile 양성혹은음성으로판정하였다. 3) ChromID C. difficile agar culture ChromID C. difficile agar는다른그람양성, 음성세균과진균의배양은억제하면서 C. difficile 배양을촉진하는선택배지로, C. difficile이배양될경우회색혹은검은색의불규칙한경계를가진집락이특징적으로나타난다. 이연구에서는다른세균들의성장을억제하기위해대변검체를알코올처리한후배지에획선접종하였고 [18, 19], 37 C, 무산소환경에서 24시간배양한후결과를판독하였다. 균이자란경우그람염색을통해그람양성간균임을확인하였으며, 집락이나그람염색소견이 C. difficile 소견과일치하는경우양성으로판정하였다. 배양된균이 C. difficile 소견과일치하지않는경우에는 Vitek 2 ANC ID Card (biomérieux SA) 를사용하여 Vitek 2 (biomérieux SA) 자동화장비를통해균종을동정하여양성혹은음성으로판정하였다. 4) 통계및자료분석 Xpert 검사와비교하여 VIDAS 검사법과 ChromID 배양법의일치율과 Cohen s kappa 계수를계산하였다 [20]. 또한 Xpert 검사가양성인경우, 혹은 Xpert 검사가음성이지만다른검사법중하나이상이양성이면서영상학적검사혹은내시경검사에서 PMC의특징적인소견이관찰된경우를 CDI의진단기준으로정의하여각검사법의민감도와특이도를확인하였다. 통계학적분석에는 SPSS 20.0 (IBM Corporation, NY, USA) 프로그램을사용하였다. 결과 1. 검사간일치율 전체검체중 1,027검체 (75.3%) 는세검사모두음성이었고, 101 검체 (7.4%) 는세검사모두양성으로세검사의전체일치율은 82.7% 였다 (Table 1). Xpert 검사양성은 287건이었고, VIDAS 검사만양성인경우중 PMC 소견이관찰된경우가한건, 배양법만양성인경우중 PMC 소견이관찰된경우가세건으로 CDI로진단된경우는총 291건 (21.3%) 이었다. 74

3 Table 1. Summary of the results of three diagnostic assays for CDI from 1,363 stool samples Assay VIDAS Toxin A/B assay Xpert C. difficile assay ChromID C. difficile agar culture N (%) Result Negative Negative Negative 1,027 (75.3) Positive Negative Negative 8 (0.6) Negative Positive Negative 71 (5.2) Positive Positive Negative 11 (0.8) Negative Negative Positive 41 (3.0) Positive Negative Positive 0 (0.0) Negative Positive Positive 104 (7.6) Positive Positive Positive 101 (7.4) Xpert positive 287 (21.1) PMC findings in radiologic/endoscopic test* 4 (0.3) True positive cases 291 (21.3) Total 1,363 (100.0) *In discrepant cases with a negative Xpert C. difficile result, CDI was diagnosed if radiologic and/or endoscopic findings of PMC were present. Table 2. Agreement on results in comparison with the Xpert C. difficile assay OPA PPA NPA κ coefficient % (95% CI) P value VIDAS ( ) <0.05 ChromID ( ) <0.05 Abbreviations: OPA, overall percentage agreement; PPA, positive percentage agreement; NPA, negative percentage agreement; CI, confidence interval. Table 3. Performance of the VIDAS Toxin A/B assay and ChromID C. difficile culture Sensitivity Specificity PPV NPV % (95% CI) VIDAS 38.8 ( ) 99.3 ( ) 94.2 ( ) 85.7 ( ) ChromID 71.5 ( ) 96.5 ( ) 84.6 ( ) 92.6 ( ) Abbreviations: PPV, positive predictive value; NPV, negative predictive value; CI, confidence interval. 각검사간비교시전체일치율과양성일치율, 음성일치율은 Xpert 검사법과 VIDAS 검사법의경우각각 86.6%, 39.0%, 99.3% 였으며, Xpert 검사법과 ChromID 배양법의경우각각 91.0%, 71.4%, 96.2% 였다. VIDAS 검사법과 ChromID 배양법의 Cohen s kappa 계수는각각 (P <0.05), (P <0.05) 로 Xpert 검사법과 VI- DAS 검사법은중등도의일치 (moderate agreement) 를, Xpert 검사법과 ChromID 배양법은강한일치 (substantial agreement) 를보였다 (Table 2). 2. 각검사법의성능 VIDAS 검사법의민감도와특이도는각각 38.8% (95% confidence interval, CI: %), 99.3% (95% CI: %) 였으며, ChromID 배양법은각각 71.5% (95% CI: %), 96.5% (95% CI: %) 였다 (Table 3). Xpert 검사법에서음성결과를보였으나 CDI로진단된예가 4건 (PMC 소견이관찰되면서 VIDAS 검사만양성인 1건과배양법만양성인 3건 ) 이확인되어 Xpert 검사법의민감도는 98.6% (287/291) 였다. 고찰 2000년대초북미와유럽에서고병원성 C. difficile 균주가유행하면서신속하고정확한 CDI 진단과치료의필요성이대두되었고 [21-23], 새로운검사법에대한많은연구들이이루어져왔다. 그중실시간중합효소연쇄반응등을이용한분자진단검사법은다른검사법들에비해높은민감도와특이도를가지는것으로확인되었으며 [5, 8, 9, 12], 표준검사법인독소배양법과의비교연구에서도우 수한성적을보였다 [3, 6, 7, 10, 16]. 일부문헌과가이드라인에서는 CDI 진단을위한 2, 3단계알고리즘을대체할방법으로분자진단검사법단독사용을제안하였고 [14, 16, 17], 최근 CDI 검사법에대한연구들에서는독소배양법대신분자진단검사법을표준검사법으로사용하는경우도있었다 [12, 24]. 본연구또한분자진단검사법인 Xpert 검사법이양성인경우를기준으로 CDI로진단하였다. 면역검사법인 VIDAS 검사법은본연구에서 38.8% 의낮은민감도를나타냈으며, 이는 % 의낮은민감도를보인기존문헌들의결과와도유사하였다 [2-5, 12, 13, 25]. ChromID 배양법의민감도는본연구에서 71.5% 로, 역시기존문헌들에서보고된 % 와유사한수준이었다 [13, 26]. 분자진단검사법인 Xpert 검사법은다른두검사법들과비교했을때높은양성률을보였다. VI- DAS 검사법은민감도가너무낮아 CDI 진단에사용하기에는부적합하다고생각되었으며, ChromID 배양법역시단독으로 CDI를판정하기에는민감도가낮고독소를생성하지않는 (non-toxigenic) C. difficile이배양되는위양성의가능성이존재한다. GDH 면역검사법은본연구에서는시행하지못하였으나, 많은연구들에서민감도는높지만단독으로는 CDI를판정할수없어항상다른검사들과함께사용되어야만하는한계점을가진것으로보고되었다 [2, 3, 5, 14]. 그리고한연구 [5] 에서는독소배양법을기준으로 GDH 면역검사법과독소면역검사법을결합한알고리즘을평가하였으며, 이때 C. difficile의 ribotype에때라민감도가 15.4% 에서 75.0% 까지차이를보였다. 같은연구에서 Xpert 검사법의경우 ribotype 에따라 75.0% 에서 100.0% 까지의민감도를보여면역검사법들에비해훨씬우수한성능을보여주었다. 일부문헌에서는독소검사법과배양법이모두양성인경우를 75

4 CDI 진단기준으로사용한경우가있었으며 [8-10], 이러한기준을본연구에적용하여 VIDAS 검사법과 ChromID 배양법모두양성인경우를 CDI로간주하는경우 Xpert 검사법의민감도와특이도는 96.2% (95% CI: %) 와 85.2% (95% CI: %) 로다른검사법들에비해우수한성능을보였다. 이번연구에서는 Xpert 검사법에서도위음성이존재할수있음이확인되었는데, VIDAS 검사법에서만양성으로나온 CDI가한건존재하였으며, ChromeID 배양법에서만양성인사례중 PMC 소견이보인경우도세건이존재하였다. 본연구에서 Xpert 검사음성이면서 VIDAS 검사혹은배양법에서양성인 49건중영상학적혹은내시경검사를시행한사례는 13건뿐이었고, 따라서나머지 36건중에서도영상학적혹은내시경검사를시행했다면추가로위음성사례가발견되었을것으로예상된다. 이러한위음성의가능성을가진 Xpert 검사법은불완전표준검사법 (imperfect reference test) 으로, 본연구에서 Xpert 검사법을기준으로확인한타검사법의민감도와특이도는어느정도의오류가능성을내재하고있다는한계점이있다. 그리고기존 CDI 진단을위한가이드라인에서는 C. difficile 검사에서양성이나온경우 test of cure, 즉치료효과판정을위한추적검사는권유하지않고있으나이번연구에서는이러한추적검사들을모두배제하지는못한한계가있었다 [2, 14]. CDI의진단과치료가늦어질경우환자의임상경과가악화되고재원기간이증가할위험이있으므로항생제관련설사환자에서신속하고정확한 CDI의진단은매우중요하다. 본연구를통해분자진단검사법의우수한성능을입증한기존의연구들을뒷받침하는결과를얻을수있었으며, 이러한검사법이 CDI의초기진단에결정적인역할을할수있을것으로생각된다. 하지만우수한성능이여러문헌들에서입증되었음에도불구하고분자진단검사법이다단계진단알고리즘을완전히대체하지못하는이유는면역검사법에비해높은비용과긴검사소요시간 (turn-around time, TAT), 그리고여러문헌들에서지적된위양성의문제때문이다 [6, 9, 10]. 각 CDI 검사법의소요비용과 TAT를조사한일부연구들 [12, 15-17] 에의하면분자진단검사법의비용은면역검사법의약 2-10배이고, TAT 역시 Xpert 검사법외의분자진단검사법은면역검사법에비해긴편으로이러한단점들이분자진단검사법을 CDI 진단의초기검사로사용하는데장애가되어왔다. 그런데최근한연구 [15] 에서는면역검사법만으로초기검사를시행한경우 CDI 진단지연에의해초기치료가늦어질수있고, 이로인한원내전파의증가와재원기간연장이결국전체비용을증가시킬수있다는점을언급하고있다. 이러한점들을고려할때분자진단검사법을초기에시행함으로써 CDI의진단과치료에필요한전체비용을평균적으로감소시킬수있을것이다. 그리고 Xpert 검사법은다른 분자진단검사법들과는달리면역검사법과큰차이가없는짧은검사소요시간을가지고있다는장점이있으며, 다른신속분자진단검사법들도지속적으로상용화되고있다 [12, 17]. 따라서저자는 CDI 진단에있어초기에면역검사법을우선시행하는기존의다단계알고리즘을사용하기보다즉시및개별검사가가능한신속분자진단검사법을우선시행하는것이 CDI의빠른진단및치료에도움이될것으로판단하였다. 영상학적검사와내시경검사역시 CDI의진단에도움을줄수는있지만, 방사선노출과침습적시술에따른합병증의위험성이존재하므로검사실적검사를우선시행한후그결과에따라제한적으로시행하는것이비용대비효율적일것으로사료된다. 그리고추가연구들에서분자진단검사법을비롯한여러검사실적검사법들의결과와함께영상학적혹은내시경검사결과를확인및비교해본다면각검사법들의성능과효용성을좀더정확히평가하는데도움이될것이라생각된다. 요약 배경 : Clostridium difficile은항생제사용후발생하는위막성대장염 (pseudomembranous colitis, PMC) 의주요원인균이다. C. difficile 감염 (C. difficile infection, CDI) 의진단을위해서는이전항생제사용력, 지속적인설사등의병력을가지는환자를대상으로 C. difficile 독소를검출하는것이필수적이다. 본연구에서는한대학병원임상미생물검사실로 CDI 진단을위해의뢰된대변검체 1,363개를대상으로시행된세가지방법의 C. difficile 검사결과를분석하여각검사법들의성능과실제유용성을확인하고자하였다. 방법 : 각검체는면역검사법인 VIDAS C. difficile Toxin A&B (bio- Mérieux SA, France) 검사와실시간중합효소연쇄반응을기반으로하는 Xpert C. difficile assay (Cepheid, USA) 검사및 ChromID C. difficile agar (biomérieux SA, France) 를이용한배양검사를모두시행하였다. CDI의진단기준은 Xpert 검사결과가양성인경우와 VIDAS 검사법이나배양법두가지중하나이상이양성이면서영상학적검사혹은내시경검사에서 PMC가진단된경우로정의하였다. 결과 : 전체검체중 1,027검체 (75.3%) 는세검사모두음성이었고, 101검체 (7.4%) 는세검사모두양성으로세검사의전체일치율은 82.7% 였다. 또한최종적으로 CDI로진단된경우는총 291건 (21.3%) 이였다. 각검사법의민감도와특이도는 VIDAS 검사법의경우 38.8%, 99.3% 였으며, ChromID 배양법은각각 71.5%, 96.5% 였다. VIDAS 검사법과배양법의경우단독으로사용하기에는민감도면에서부족한결과를보였고, Xpert 검사법은높은민감도 (98.6%, 287/291) 76

5 를보였다. 결론 : CDI 진단에있어초기검사법으로 Xpert 검사법과같은신속분자진단검사법을시행하는것이효율적일것으로생각되었다. 이해관계 저자들은본연구와관련하여해당회사와이해관계가없음. REFERENCES 1. Bartlett JG, Chang TW, Gurwith M, Gorbach SL, Onderdonk AB. Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. N Engl J Med 1978;298: Bagdasarian N, Rao K, Malani PN. Diagnosis and treatment of Clostridium difficile in adults: a systemic review. JAMA 2015;313: Swindells J, Brenwald N, Reading N, Oppenheim B. Evaluation of diagnostic tests for Clostridium difficile infection. J Clin Microbiol 2010; 48: Novak-Weekley SM, Marlowe EM, Miller JM, Cumpio J, Nomura JH, Vance PH, et al.: Clostridium difficile testing in the clinical laboratory by use of multiple testing algorithms. J Clin Microbiol 2010;48: Tenover FC, Novak-Weekley S, Woods CW, Peterson LR, Davis T, Schreckenberger P, et al. Impact of strain type on detection of toxigenic Clostridium difficile: comparison of molecular diagnostic and enzyme immunoassay approaches. J Clin Microbiol 2010;48: Knetsch CW, Bakker D, de Boer RF, Sanders I, Hofs S, Kooistra-Smid AM, et al. Comparison of real-time PCR techniques to cytotoxigenic culture methods for diagnosing Clostridium difficile infection. J Clin Microbiol 2011;49: Pancholi P, Kelly C, Raczkowski M, Balada-Llasat JM. Detection of toxigenic Clostridium difficile: comparison of the cell culture neutralization, Xpert C. difficile, Xpert C. difiicile/epi, and Illuigene C. difficile assays. J Clin Microbiol 2012;50: Sloan LM, Duresko BJ, Gustafson DR, Rosenblatt JE. Comparison of real-time PCR for detection of the tcdc gene with four toxin immunoassays and culture in diagnosis of Clostridium difficile infection. J Clin Microbiol 2008;46: Karre T, Sloan L, Patel R, Mandrekar J, Rosenblatt J. Comparison of two commercial molecular assays to a laboratory-developed molecular assay for diagnosis of Clostridium difficile infection. J Clin Microbiol 2011;49: Yoo J, Lee H, Park KG, Lee GD, Park YG, Park YJ. Evaluation of 3 automated real-time PCR (Xpert C. difficile assay, BD MAX Cdiff, and IMDx C. difficile for Abbott m2000 assay) for detecting Clostridium difficile toxin gene compared to toxigenic culture in stool specimens. Diagn Microbiol Infect Dis 2015;83: Carroll KC and Loeffelholz M. Conventional versus molecular methods for the detection of Clostridium difficile. J Clin Microbiol 2011;49(S): Whang DH and Joo SY. Evaluation of the diagnostic performance of the Xpert Clostridium difficile assay and its comparison with the toxin A/B enzyme-linked fluorescent assay and in-house real-time PCR assay used for the detection of toxigenic C. difficile. J Clin Lab Anal 2014; 28: Yang JJ, Nam YS, Kim MJ, Cho SY, You E, Soh YS, et al. Evaluation of a chromogenic culture medium for the detection of Clostridium difficile. Yonsei Med J 2014;55: Sharp S and Gilligan PH. A practical guidance document for the laboratory detection of toxigenic Clostridium difficile. ASM Public and Scientific Affairs Board (PSAB) Committee on Laboratory Practices, American Society for Microbiology (ASM), Washington, D.C. (2010) pdf (Updated on Sep 2010) 15. Verhoye E, Vandecandelaere P, De Beenhouwer H, Coppens G, Cartuyvels R, Van den Abeele A, et al. A hospital-level cost-effectiveness analysis model for toxigenic Clostridium difficile detection algorithms. J Hosp Infect 2015;91: Tenover FC, Baron EJ, Peterson LR, Persing DH. Laboratory diagnosis of Clostridium difficile infection: can molecular amplification methods move us out of uncertainty? J Mol Diagn 2011;13: Brecher SM, Novak-Weekley SM, Nagy E. Laboratory diagnosis of Clostridium difficile infections: there is light at the end of colon. Clin Infect Dis 2013;57: Riley TV, Brazier JS, Hassan H, Williams K, Phillips KD. Comparison of alcohol shock enrichment and selective enrichment for the isolation of Clostridium difficile. Epidemiol Infect 1987;99: Clabots CR, Gerding SJ, Olson MM, Peterson LR, Gerding DN. Detection of asymptomatic Clostridium difficile carriage by an alcohol shock procedure. J Clin Microbiol 1989;27: Cohen J. A coefficient of agreement for nominal scales. Educ Psychol Meas 1960;20: McDonald LC, Killgore GE, Thompson A, Owens RC Jr, Kazakova SV, Sambol SP, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005;353:

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Lumbar spine

Lumbar spine CT 32 111 DOI : 10.3831/KPI.2010.13.2.111 Lumbar Spine CT 32 Received : 10. 05. 23 Revised : 10. 06. 04 Accepted : 10. 06. 11 Key Words: Disc herniation, CT scan, Clinical analysis The Clinical