Clostridium difficile, an anaerobic toxigenic bacterium, causes a severe infectious colitis that leads to significant morbidity and mortality worldwide. Both enhanced bacterial toxins and diminished host immune response contribute to symptomatic disease. C. difficile has been a well-established pathogen in North America and Europe for decades, but is just emerging in Asia. This article reviews the epidemiology, microbiology, pathophysiology, and clinical management of C. difficile. Prompt recognition of C. difficile is necessary to implement appropriate infection control practices.
Asia/epidemiology ; Clostridium Infections/*diagnosis/epidemiology/microbiology/*therapy ; Clostridium difficile/genetics/*pathogenicity ; Europe/epidemiology ; Global Health ; Humans ; North America/epidemiology

OBJECTIVEThis review discusses the current status and progress in studies on fulminant Clostridium difficile colitis (FCDC), including the definition, risk factor, diagnostic role of CT, surgical treatment, postoperative mortality, and new therapeutic strategy.

DATA SOURCESA literature search was conducted mainly in Medline and PubMed published in English between January 2000 and May 2011. The search terms were "ulminant Clostridium difficile colitis" "reatment", "urgery" and "ortality"

RESULTSRecent studies show that the overall mortality rate for FCDC remains high despite early surgical intervention. It has been difficult to identify the real value for surgical intervention in patients with FCDC due to the absence of prospective, randomized studies. Early recognition of patients with FCDC will help a clinician decide the need for treatment in an intensive care setting, multi-disciplinary consultation, and appropriate therapeutic selection. Some studies emphasize the importance of early recognition and emergent surgery at a less severe stage. Monoclonal antibody therapy and intravenous immunoglobulin treatment may be useful for the treatment of FCDC.

CONCLUSIONSPresent studies do not provide strong evidence for guiding the surgical treatment of FCDC; hence, creation of collaborative research networks is crucial in order to undertake large prospective multi-center studies for improvement in overall survival.

Antibodies, Monoclonal ; therapeutic use ; Clostridium Infections ; drug therapy ; surgery ; Clostridium difficile ; drug effects ; pathogenicity ; Humans ; Immunoglobulins ; therapeutic use

BACKGROUNDClostridium difficile-associated diarrhea (CDAD) is a major public health problem because of significant morbidity and mortality, and many clinicians pay attention to Lactobacillus as a potentially effective treatment. The purpose of this meta-analysis was to evaluate the efficacy of Lactobacillus in the prevention of CDAD.

METHODSThe databases MEDLINE, the Cochrane Central Register of Controlled Trials, metaRegister of Controlled Trials, National Institutes of Health, CNKI, VIP, and Wanfang data were searched to locate all reported randomized controlled trials (RCT) from 1990 to December 2012. Only RCT in English and Chinese using Lactobacillus for the prevention of documented CDAD were considered for study inclusion. The data was analyzed by Review Manager and SPSS software.

RESULTSSeven placebo-controlled RCTs that evaluated the prevention of CDAD, which included 1486 subjects, accorded with inclusion and exclusion criteria. The mean age of the subjects ranged from 4.15 to 64.75 years and the proportion of male subjects ranged from 42.0% to 59.1%. The total daily dose of Lactobacillus ranged from 1.2×10(9)-1.2×10(12) colonyforming units (CFU). A low risk of bias was attributed to two studies and four studies evaluated a medium-level risk of bias. The combined risk ratio (RR) of developing CDAD was significantly lower in subjects who received Lactobacillus compared with subjects who received placebo (RR 0.38, 95% confidence interval (CI) 0.22-0.67). A combination regimen of Lactobacillus acidophilus (L. acidophilus) and Lactobacillus casei (L. casei) (RR 0.05, 95% CI 0.01-0.36) showed significant effect sizes for the prevention of CDAD, while single regimens of Lactobacillus plantarum (L. plantarum) and Lactobacillus rhamnosus (L. rhamnosus) did not. Across all trials, positive significant effects of Lactobacillus were observed in the elderly subgroup (RR 0.05, 95% CI 0.01-0.36). Whether the 1×10(12)-9×10(12) CFU/d Lactobacillus could prevent CDAD significantly or not was unclear.

CONCLUSIONThere is a sufficient evidence to recommend Lactobacillus (L. acidophilus and L. casei) as a prevention therapy for CDAD.

Clostridium difficile ; pathogenicity ; Diarrhea ; microbiology ; prevention & control ; Humans ; Lactobacillus ; physiology ; Randomized Controlled Trials as Topic

OBJECTIVEClostridium difficile is an obligate anaerobic Gram-positive bacillus, it can cause Clostridium difficile-associated diarrhea (CDAD). This study aimed to investigate the virulence genes and clinical features of CDAD in children by gene detection.

METHODFrom May 2012 to January 2013, the 121 inpatients in Beijing Children's Hospital who suffered from diarrhea after antibiotics treatment were detected for Clostridium difficile virulence genes including the five genes for pathogenic loci (tcdA, tcdB, tcdC, tcdD, tcdE) and the genes for binary toxin CDT (cdtA and cdtB) using polymerase chain reaction (PCR) in order to research the clinical features of CDAD, and analyze target products by sequencing.

RESULTSIn the 121 children with diarrhea, 60 (49.6%) were toxin B-positive,including 12 toxin A-positive and toxin B-positive (A+B+), 48 toxin A-negative but toxin B-positive (A-B+). The toxin A-positive but toxin B-negative (A+B-) specimens or binary toxin (cdtA and cdtB)-positive specimens were not detected. Of 60 tcdB-positive specimens, tcdC, tcdD and tcdE positive specimens were 24 (40%), 25 (42%), 24 (40%), respectively. The sequencing results of tcdA, tcdB, tcdC, tcdD, and tcdE gene were consistent with the reference sequence. In the 60 children with CDAD, infants (≤3 years) accounted for 62% (37/60). The duration of diarrhea was 3-77 days, and 42 (70%) cases had acute diarrhea; 39 (65%) patients had fever, 40 (67%) had anemia, 36 (60%) had abnormal white blood cell count, 30 (50%) had hypoalbuminemia, 25 (42%) had elevated C-reactive protein (CRP). The level of CRP in positive group was significantly higher compared to the negative group (45.0(16.0,89.0) mg/L vs. 19.0(14.5,41.5) mg/L, Z=-2.008, P=0.045). The level of plasma albumin in positive group was significantly lower compared to the negative group (35.3(29.7,39.8) g/L vs. 38.5(33.9,41.5) g/L, Z=-2.610, P=0.009). There were no significant differences in gender, age, duration of diarrhea, hospital staytime, time of using antibiotics and laboratory test between A+B+ group and A-B+ group (all P>0.05).

CONCLUSIONThe main virulence genotype of Clostridium difficile was toxin A-negative but toxin B-positive in this research. The clinical features of CDAD in children were acute diarrhea with fever. Laboratory examination showed that white blood cell count was abnormal, CRP was increased, hemoglobin and plasma albumin were reduced.

Anti-Bacterial Agents ; Bacterial Toxins ; genetics ; Beijing ; C-Reactive Protein ; Child ; Clostridium Infections ; microbiology ; Clostridium difficile ; genetics ; pathogenicity ; Diarrhea ; microbiology ; Fever ; Genes, Bacterial ; Genotype ; Humans ; Infant ; Leukocyte Count ; Polymerase Chain Reaction ; Virulence ; genetics

The incidence and severity of Clostridium difficile infection (CDI) has increased over the past decades. It is related to the emergence of hypervirulent strains and increased use of antibiotics. The incidence of refractory CDI to standard therapies and the risk for recurrent CDI are also increasing. Current guidelines recommend the first recurrence to be treated with the same agent used for the initial episode. However, data are lacking to support any particular treatment strategy for severe refractory CDI or cases with multiple recurrence. Treatments currently available for CDI are inadequate to prevent recurrence. Widely used method for managing a subsequent recurrence involves tapering followed by pulsed doses of vancomycin. Other potentially effective strategies for recurrent CDI are use of other antibiotics such as fidaxomicin, nitazoxanide, rifaximin, tigecycline, and teicoplanin. There are efforts to recover gut microflora and to optimize immune response to CDI. These include use of probiotics, fecal microbiota transplantation, intravenous immunoglobulin, monoclonal antibodies directed against C. difficile toxins, and active vaccination. However treatment of patients with refractory CDI and those with multiple CDI recurrences is based on limited clinical evidence, and there is an ongoing need for continued research to improve the outcomes these patients.
Anti-Bacterial Agents/therapeutic use ; Antibodies, Monoclonal/immunology/therapeutic use ; Clostridium difficile/drug effects/pathogenicity ; Enterocolitis, Pseudomembranous/*drug therapy ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Probiotics/therapeutic use ; Recurrence ; Vancomycin/therapeutic use

Advances in sequencing technology and the development of metagenomics have opened up new ways to investigate the microorganisms inhabiting the human gut. The intestinal microbiota confer protection against pathogens, contribute to the maturation of the immune system, and regulate host metabolism. The composition of gut microbiota in early life is influenced by mode of birth, diet, and antibiotics. Decreased biodiversity and alterations in the composition of the intestinal microbiota have been observed in many diseases including obesity, neonatal necrotizing enterocolitis, inflammatory bowel disease, and recurrent Clostridium difficile infection. Therapeutic options for the diseases linked to imbalance in the microbiota include modifying the gut microbiota through diet, probiotics, and fecal transplants.
Animals ; Anti-Bacterial Agents/therapeutic use ; Clostridium difficile/isolation & purification/pathogenicity ; Enterocolitis, Pseudomembranous/drug therapy/microbiology/pathology ; Fatty Liver/etiology/microbiology ; Humans ; Inflammatory Bowel Diseases/etiology/microbiology ; Intestines/*microbiology ; *Microbiota ; Obesity/etiology/microbiology

In order to investigate the incidence, clinical and microbiologic characteristics of Clostridium difficile infection (CDI) in Korea, a prospective observational study was performed. From September 2008 through January 2010, all patients whose stool was tested for toxin assay A&B and/or C. difficile culture were studied for clinical characteristics. Toxin types of the isolates from stool were tested. The mean incidence of CDI per 100,000 patient-days was 71.6 by month (range, 52.5-114.0), and the ratio of CDI to antibiotic-associated diarrhea was 0.23. Among 200 CDI patients, 37.5% (75/200) was severe CDI based on severity score. Clinical outcome of 189 CDI was as followed; 25.9% (49/189) improved without treatment, 84.3% (118/140) achieved clinical cure and attributed mortality was 0.7% (1/140) with the treatment. Recurrence rate was 21.4% (30/140) and cure without recurrence was 66.4% (93/140). The most common type of toxin was toxin A-positive/toxin B-positive strain (77.5%), toxin A-negative/toxin B-positive strains or binary toxin-producing strains comprised 15.4% or 7.1%, respectively. In conclusion, the incidence of CDI in Korea is a little higher than other reports during the non-epidemic setting. We expect that the change of epidemiology and clinical severity in CDI can be evaluated based on these results.
Aged ; Bacterial Proteins/analysis ; Bacterial Toxins/analysis ; Clostridium Infections/*epidemiology/physiopathology ; Clostridium difficile/*isolation & purification/*pathogenicity ; Diarrhea/epidemiology/microbiology ; Enterocolitis, Pseudomembranous/*epidemiology/microbiology/pathology ; Enterotoxins/analysis ; Feces/microbiology ; Female ; Hospitals ; Humans ; Incidence ; Male ; Metronidazole/therapeutic use ; Middle Aged ; Prospective Studies ; Recurrence ; Republic of Korea/epidemiology ; Treatment Outcome ; Vancomycin/therapeutic use

BACKGROUND/AIMS: It has been suggested that chronic kidney disease (CKD) is a risk factor for Clostridium difficile infection (CDI) and is associated with increased mortality among patients infected with C. difficile. However, recent studies of the clinical impact of CKD on CDI in Asians are still insufficient. We sought to determine the relationship between CKD and CDI in a Korean population. METHODS: This was a single-center, retrospective case-control study. In total, 171 patients with CDI were included as cases and 342 age- and gender-matched patients without CDI were used as controls. We compared the prevalence of CKD in the study sample and identified independent risk factors that could predict the development or prognosis of CDI. RESULTS: Independent risk factors for CDI included stage IV to V CKD not requiring dialysis (odds ratio [OR], 2.90) and end-stage renal disease requiring dialysis (OR, 3.34). Patients with more advanced CKD (estimated glomerular filtration rate < 30) and CDI showed higher in-hospital mortality and poorer responses to the initial metronidazole therapy. CONCLUSIONS: More advanced CKD is an independent risk factor for CDI and is associated with higher in-hospital mortality and poor treatment responses in CDI patients. Thus, in CKD patients, careful attention should be paid to the occurrence of CDI and its management to improve the outcome of CDI.
Aged ; Anti-Infective Agents/therapeutic use ; Chi-Square Distribution ; Clostridium difficile/*pathogenicity ; Enterocolitis, Pseudomembranous/diagnosis/drug therapy/*microbiology/mortality ; Female ; Hospital Mortality ; Humans ; Kidney Failure, Chronic/*complications/diagnosis/therapy ; Logistic Models ; Male ; Metronidazole/therapeutic use ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Prevalence ; Renal Dialysis ; Renal Insufficiency, Chronic/*complications/diagnosis/mortality/therapy ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Treatment Outcome