Detection and characterization of Clostridium difficile infections tracking the trends of Clostridium difficile culture

Ock, Min-Su,Oh, Jin-Sun,Kim, Hwa-Jung,Lyu, Yong-Man,Lee, Moo-Song Korean Society for Quality in Health Care 2016 한국의료질향상학회지 Vol.22 No.2

Objectives: In this study, we examined the validity of Clostridium difficile culture results as a proxy measure of Clostridium difficile infection, and inferred the epidemiologic characteristics of Clostridium difficile infection by tracking the trends of Clostridium difficile culture results. Methods: We reviewed the medical records to figure out the actual possibilities of Clostridium difficile infection of those with positive or negative results of Clostridium difficile culture during the time span from January 2012 to March 2012. We calculated the positive and negative predictive value of Clostridium difficile culture results for Clostridium difficile infection. Furthermore, epidemiologic characteristics of Clostridium difficile infection in a tertiary general hospital in 2012 were analyzed. Result: The estimated positive predictive value of Clostridium difficile culture tests for Clostridium difficile infection was 100%, and the estimated negative predictive value was around 94.4~99.3% depending on the cutoff value of possibility of Clostridium difficile infection. A total of 622 cases were identified as Clostridium difficile infection in a tertiary general hospital in 2012 and there were 4.9 patients with Clostridium difficile infection per 1,000 inpatients. Conclusion: In conclusion, we identified that Clostridium difficile culture results can be used as a proxy measure of Clostridium difficile infection.

REVIEW : Clostridium difficile Infection: What`s New?

( Geom Seog Seo ) 대한장연구학회 2013 Intestinal Research Vol.11 No.1

Since 2000, Clostridium difficile infection has increased substantially in both hospital-acquired and community-acquired diarrhea, not only in North America but also in Europe. There was a steady increase in the incidence and severity of C. difficile infection over the past decade, associated with significantly higher morbidity and mortality. The major risk factors for C. difficile infection appear to be the use of new antimicrobial therapy, long-term hospitalization in old age and emerging hypervirulent strains, such as various ribotypes. Rapid and accurate diagnosis of C. difficile infection is necessary for appropriate treatment as well as reliable epidemiological data. Currently available treatment options are withdrawal of the suspected offending antibiotics and then treating patients with highly effective antibiotics for C. difficile. Multiple recurrence or acute fulminant C. difficile infection could be treated with fecal microbiota transplantation. Promising therapies for treating C. difficile infection should always be equipped with high efficacy and safety in the future. (Intest Res 2013;11:1-13)

Clostridium difficile Infection: What’s New?

서검석,박성훈,황기은,박도심,김학렬,윤권하 대한장연구학회 2013 Intestinal Research Vol.11 No.1

Since 2000, Clostridium difficile infection has increased substantially in both hospital-acquired and community-acquired diarrhea,not only in North America but also in Europe. There was a steady increase in the incidence and severity of C. difficile infection over the past decade, associated with significantly higher morbidity and mortality. The major risk factors for C. difficile infection appear to be the use of new antimicrobial therapy, long-term hospitalization in old age and emerging hypervirulent strains, such as various ribotypes. Rapid and accurate diagnosis of C. difficile infection is necessary for appropriate treatment as well as reliable epidemiological data. Currently available treatment options are withdrawal of the suspected offending antibiotics and then treating patients with highly effective antibiotics for C. difficile. Multiple recurrence or acute fulminant C. difficile infection could be treated with fecal microbiota transplantation. Promising therapies for treating C. difficile infection should always be equipped with high efficacy and safety in the future. (Intest Res 2013;11:1-13)

Clostridium difficile 감염의 발생률 및 임상 양상; 단일기관 연구

이진호 ( Jin Ho Lee ),이수연 ( Su Yeon Lee ),김유선 ( You Sun Kim ),박선욱 ( Sun Wook Park ),박성원 ( Sung Won Park ),조소영 ( So Young Jo ),류수형 ( Soo Hyung Ryu ),이정환 ( Jung Hwan Lee ),문정섭 ( Jeong Seop Moon ),황동희 ( Don 대한소화기학회 2010 대한소화기학회지 Vol.55 No.3

목적: Clostridium difficile 감염(C. difficile infection, CDI)은 병원성 설사의 가장 흔한 원인이며, 항생제를 많이 사용하거나 주위 환경이 C. difficile 포자로 감염된 경우 발생빈도는 증가한다. 최근 유럽과 북미에서 CDI의 발생률이 증가하고 있어 저자들은 국내에서 CDI의 발생률의 변화에 대해 파악하고자 했다. 대상 및 방법: 2003년 1월부터 2008년 12월까지 6년간 서울백병원에서 입원한 환자 중 CDI로 진단된 18세 이상 환자들을 대상으로 후향 분석하였다. CDI의 진단은 설사와 함께 대변검사에서 C. difficile toxin이 양성이거나 C. difficile이 동정된 경우 또는 위막 대장염이 진단된 경우로 정하였다. 2003-2005년을 초반기군으로, 2006- 2008년을 후반기군으로 나누어 발생률, 재발률 및 임상 경과를 비교했다. 결과: CDI의 발생률은 전반기군에서 입원 환자 만 명당 21.73명이었으며 후반기군은 입원환자 만 명당 71.71명으로 초반기군보다 의미 있게 증가하였다(p<0.01). CDI 발생 시 재원기간은 후반기군에서 전반기군에 비해 짧았고(p<0.01) 원인 항생제로는 cephalosporin이 가장 높은 비율을 차지하였다. 재발률은 두 군 사이에 차이가 없었으며(p=0.973), 재발과 연관된 인자는 혈청 알부민 수치였다. 결론: 이번 연구는 6년 동안 CDI의 증가된 발생률을 관찰한 단일 기관 연구이다. CDI 발생률이 증가하고 있다는 인식이 이 질환의 관리에 중요한 초석이다. Background/Aims: Clostridium difficile is the predominant cause of nosocomial diarrhea. Recently, the incidence of Clostridium difficile infection (CDI) increases in Europe and North America. A retrospective study was performed to evaluate the change of incidence and clinical features of CDI in Korea. Methods: From January 2003 to December 2008, inpatients diagnosed with CDI in Seoul Paik hospital were enrolled. The diagnosis of CDI was made when patients complained diarrhea with any positive results in C. difficile toxin assay, stool culture, or endoscopy. The incidence, recurrence rate, and clinical features were compared between early period (2003-2005) and late period (2006-2008). Results: The incidence of CDI was 21.73 cases per 10,000 admitted patients in early period group, and significantly increased to 71.71 cases per 10,000 admitted patients in late period group (p<0.01). The hospital stay duration at the time of CDI diagnosis was shorter in late period group. Cephalosporin had the highest ratio as the causative antibiotics of CDI. However, there was no difference in recurrence rate between early and late period groups. Recurrence associated clinical factor was serum albumin level. Conclusions: The incidence of CDI showed increasing tendency during recent 6 years. The awareness of increasing disease burden is the first step in control of CDI. (Korean J Gastroenterol 2010;55:175-182)

Case report : A Case of Toxic Megacolon Caused by Clostridium difficile Infection and Treated with Fecal Microbiota Transplantation

( Tae Geun Gweon ),( Kyung Jin Lee ),( Dong Hoon Kang ),( Sung Soo Park ),( Kyung Hoon Kim ),( Hyeon Jin Seong ),( Tae Hyun Ban ),( Sung Jin Moon ),( Jin Su Kim ),( Sang Woo Kim ) The Editorial Office of Gut and Liver 2015 Gut and Liver Vol.9 No.2

Toxic megacolon is a rare clinical complication of fulminant Clostridium difficile infection. The mortality rate of fulminant C. difficile infection is reported to be as high as 50%. Fecal microbiota transplantation is a highly effective treatment in patients with recurrent or refractory C. difficile infection. However, there are few published articles on the use of such transplantation for fulminant C. difficile infection. Here, we report on a patient with toxic megacolon complicated by C. difficile infection who was treated successfully with fecal microbiota transplantation. (Gut Liver, 2015;9:247-250)

Rapid and accurate diagnosis of Clostridium difficile infection by real-time polymerase chain reaction

Pil Hun Song,Jung Hwa Min,You Sun Kim,Soo Yeon Jo,Eun Jin Kim,Kyung Jin Lee,Jeonghun Lee,Hyun Sung,Jeong Seop Moon,Dong Hee Whang 대한장연구학회 2018 Intestinal Research Vol.16 No.1

Background/Aims: The incidence and severity of Clostridium difficile infection (CDI) have increased worldwide, resulting ina need for rapid and accurate diagnostic methods. Methods: A retrospective study was conducted to compare CDI diagnosismethods between January 2014 and December 2014. The stool samples, which were obtained in presumptive CDI patients,were compared for their diagnostic accuracy and rapidity, including real-time polymerase chain reaction (PCR) of toxin genes,C. difficile toxin assay, and culture for C. difficile . Results: A total of 207 cases from 116 patients were enrolled in this study and117 cases (56.5%) were diagnosed as having CDI. Among the 117 cases, the sensitivities of real-time PCR, C. difficile toxin assay,and culture for C. difficile were 87.2% (102 cases; 95% CI, 80.7%−92.8%), 48.7% (57 cases; 95% CI, 41.0%−59.8%), and 65.0% (76cases; 95% CI, 60.2%−78.5%), respectively (P <0.005). Notably, 34 cases (29.0%) were diagnosed with CDI by real-time PCR only. The time required to obtain results was 2.27 hours (136.62±82.51 minutes) for real-time PCR, 83.67 hours (5,020.66±3,816.38minutes) for toxin assay, and 105.79 hours (6,347.68±3,331.46 minutes) for culture (P <0.005), respectively. Conclusions: Weconfirmed that real-time PCR of toxin genes is the most effective diagnostic method for accurate and early diagnosis of CDI. Italso helps to diagnose hypervirulent CDI, such as ribotype 027 infection.

노인층에서 Clostridium difficile 감염 약물사용평가 및 비호전군에 대한 영향인자

노현정,함정연,이자균,이정연 한국임상약학회 2018 한국임상약학회지 Vol.28 No.3

Objective: Clostridium difficile Infection (CDI) is one of the common nosocomial infections. As elderly population increases, theproper treatment has been emphasized. We investigated the risk factors associated with CDI unimprovement in elderly patients. Furthermore, we performed drug use evaluation of old CDI patients and oldest-old CDI patients. Methods: It was a retrospectivestudy using electronic medical record at Kangbuk Samsung Medical Center (KBSMC) from January 2016 to December 2017. Seventythree patients aged 65 years or older, diagnosed with CDI by Clostridium difficile Toxin B Gene [Xpert] were screened and theywere assessed for risk factors regarding unimprovement status. We also evaluated drug use evaluation in old patients (65≤age<80)and oldest-old patients (80≤age) by assessing the use of initial therapy, severity, dose, route, treatment course, days of use, totaldays of use and treatment outcome of initial therapy. Results: Out of 73 patients aged over 65 years, four patients were excludedbecause they did not receive any treatment. There were 31 improved patients and 38 unimproved patients after initial therapy. Wewere able to find out patients with surgical comorbidity or endocrine comorbidity (especially, diabetes mellitus) had 2.885 more riskof becoming unimproved than those patients without surgical comorbidity or endocrine comorbidity. Drug use evaluation for CDIwas generally fair, but vancomycin as initial therapy is more recommended than metronidazole. Conclusion: Although age,antibiotics exposure, use of antacids are all important risk factors for CDI, our result did not show statistical significance for theserisk factors. However, the study is meaningful because the number of elderly population keeps increasing and recently updatedguideline suggests the use of vancomycin as drug of choice for CDI.

소아에서 발생한 Clostridium difficile 관련 질환의 역학과 임상양상: 지역사회감염과 원내감염의 비교

조혜정,류일,선용한,조강호,손동우,차한,Cho, Hye-Jung,Ryoo, Eell,Sun, Yong-Han,Cho, Kang-Ho,Son, Dong-Woo,Tchah, Hann 대한소아소화기영양학회 2010 Pediatric gastroenterology, hepatology & nutrition Vol.13 No.2

목 적: 최근 소아에서의 지역사회 획득 Clostridium difficile 관련질환(CDAD)은 증가하는 것으로 보고된다. 그러나 아직 소아에서 발생한 CDAD에 대한 정보는 부족한 실정이다. 저자들은 소아 CDAD환자에서 지역사회감염(CA-CDAD)과 병원감염(HA-CDAD)의 역학과 임상양상의 차이를 비교하여 알아보고자 하였다. 방 법: 2008년 4월부터 2010년 3월까지 가천의대 길병원 소아청소년과에 내원한 환자들의 의무기록을 후향적으로 분석하여 소화기계 증상을 가지고 있으면서 C. difficile 독소 A, B 또는 C. difficile 배양검사에서 양성으로 확인된 경우 CDAD로 진단하였다. 결 과: 총 61명(남 32, 여 29)의 환자가 연구에 포함되었고, 평균연령은 3.79${\pm}$4.54세였으며, 1세 미만이 22명(36.1%)으로 가장 많았다. 전체 중 23명(37.7%)의 환자만이 증상 발현 3개월 이내에 항생제를 투여 받은 적이있었다. 총 61명의 환자 중 CA-CDAD군이 41명, HA-CDAD군이 20명이었고, 나이, 성별, 증상, 검사실소견, 회복기간, 합병증 발생 및 재발률은 두 군 간에 유의한 차이가 없었으나 항생제 노출 여부는 HACDAD의 발생과 관련이 있었다. 결 론: 소화기계 증상을 가지고 외래에 내원한 영아와 어린 소아에서 항생제 노출력이 없는 CA-CDAD의 발생이 증가하고 있다. 신속하게 검사를 시행하는 것이 정확한 진단과 치료를 위해 요구된다. Purpose: Recent studies have reported an increase in the incidence of community-acquired Clostridium difficile-associated disease (CA-CDAD) among children. There is an overall lack of information on CA-CDAD in the pediatric population. The aim of our study was to compare the epidemiologic and clinical features between CA-CDAD and hospital-acquired C. difficile-associated disease (HA-CDAD) in children. Methods: We retrospectively reviewed the medical records of all patients who were diagnosed with C. difficile-associated disease (CDAD) at Gil Hospital between April 2008 and March 2009. The diagnosis of CDAD was made when patients with gastrointestinal symptoms had positive results for C. difficile toxins A and B assay or stool culture. Results: Sixty-one (male, 32 and female, 29) patients were included. The mean age was 3.79${\pm}$4.54 years. Of the 61 patients, 22 (36.1%) were <1 year of age. Twenty-three patients (37.7%) had a history of antibiotic exposure in the previous 3 months. Forty-one patients (67.2%) were diagnosed with CA-CDAD. There were no significant differences in age, gender, symptoms, laboratory findings, recovery period, complications, and recurrence between the CA-CDAD and HA-CDAD groups. On the other hand, exposure to antibiotics was significantly more frequent among patients in the HA-CDAD group (p=0.005). Conclusion: This study suggests that the occurrence of CA-CDAD is increasing in the pediatric population, especially in younger children with no history of exposure to antibiotics and in outpatients. Awareness of the increasing incidence of CA-CDAD and prompt investigation of C. difficile in susceptible patients is needed to avoid misdiagnosis and for appropriate therapy.

Epidemiology and Factors Related to Clinical Severity of Acute Gastroenteritis in Hospitalized Children after the Introduction of Rotavirus Vaccination

Kim, Ahlee,Chang, Ju Young,Shin, Sue,Yi, Hana,Moon, Jin Soo,Ko, Jae Sung,Oh, Sohee KOREAN ACADEMY OF MEDICAL SCIENCE 2017 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.32 No.3

<P>We aimed to investigate epidemiology and host- and pathogen-related factors associated with clinical severity of acute gastroenteritis (AGE) in children after rotavirus vaccination introduction. Factors assessed included age, co-infection with more than 2 viruses, and virus-toxigenic <I>Clostridium difficile</I> co-detection. Fecal samples and clinical information, including modified Vesikari scores, were collected from hospitalized children with AGE. The presence of enteric viruses and bacteria, including toxigenic <I>C. difficile,</I> was detected by polymerase chain reaction (PCR). Among the 415 children included, virus was detected in stool of 282 (68.0%) children. Co-infection with more than 2 viruses and toxigenic <I>C. difficile</I> were found in 24 (8.5%) and 26 (9.2%) children with viral AGE, respectively. Norovirus (n = 130) infection, including norovirus-associated co-infection, was the most frequent infection, especially in children aged < 24 months (<I>P</I> < 0.001). In the severity-related analysis, age < 24 months was associated with greater diarrheal severity (<I>P</I> < 0.001) and modified Vesikari score (<I>P</I> = 0.001), after adjustment for other severity-related factors including rotavirus status. Although the age at infection with rotavirus was higher than that for other viruses (<I>P</I> = 0.001), rotavirus detection was the most significant risk factor for all severity parameters, including modified Vesikari score (<I>P</I> < 0.001). Viral co-infection and toxigenic <I>C. difficile</I> co-detection were not associated with any severity-related parameter. This information will be helpful in the management of childhood AGE in this era of rotavirus vaccination and availability of molecular diagnostic tests, which often lead to the simultaneous detection of multiple pathogens.</P>

A chimeric protein comprising the glucosyltransferase and cysteine proteinase domains of toxin B and the receptor binding domain of toxin A induces protective immunity against <i>Clostridium difficile</i> infection in mice and hamsters

Wang, Yuan-Kai,Yan, Ya-Xian,Kim, Hyeun Bum,Ju, Xianghong,Zhao, Song,Zhang, Keshan,Tzipori, Saul,Sun, Xingmin TaylorFrancis 2015 Human Vaccines & Immunotherapeutics Vol.11 No.9

<P><I>Clostridium difficile</I> is the major cause of hospital-acquired infectious diarrhea and colitis in developed countries. The pathogenicity of <I>C. difficile</I> is mainly mediated by the release of 2 large potent exotoxins, toxin A (TcdA) and toxin B (TcdB), both of which require neutralization to prevent disease occurrence. We have generated a novel chimeric protein, designated mTcd138, comprised of the glucosyltransferase and cysteine proteinase domains of TcdB and the receptor binding domain of TcdA and expressed it in <I>Bacillus megaterium</I>. To ensure that mTcd138 is atoxic, 2 point mutations were introduced to the glucosyltransferase domain of TcdB, which essentially eliminates toxicity of mTcd138. Parenteral immunizations of mice and hamsters with mTcd138 induced protective antibodies to both toxins and provided protection against infection with the hyper-virulent <I>C. difficile</I> strain UK6.</P>