儿童艰难梭菌感染

随着广谱抗生素的大量使用,艰难梭菌相关性腹泻(CDAD)的发生率明显上升,特别是高毒力株(027/NAP1/BI)在欧美的出现及流行,已经引起全世界的关注.CDAD的临床症状轻重不一,可从轻度腹泻到致死性假膜性肠炎和中毒性巨结肠.CDAD的确诊依赖于实验室检查,包括厌氧菌培养及细胞毒性试验、细菌毒素抗原检测、毒素基因扩增检测.处理包括停用相关抗生素,尽早应用甲硝唑或万古霉素,以及益生菌药物.     

Diarrhoea in general practice: when should a Clostridium difficile infection be considered? Results of a nested case-control study

Clostridium difficile infections (CDIs) are frequent in hospitals, but also seem to increase in the community. Here, we aim to determine the incidence of CDI in general practice and to evaluate current testing algorithms for CDI. Three Dutch laboratories tested all unformed faeces (12 714) for C. difficile when diagnostic testing (for any enteric pathogen) was requested by a general practitioner (GP). Additionally, a nested case-control study was initiated, including 152 CDI patients and 304 age and sex-matched controls. Patients were compared using weighted multivariable logistic regression. One hundred and ninety-four samples (1.5%) were positive for C. difficile (incidence 0.67/10 000 patient years). This incidence was comparable to that of Salmonella spp. Compared with diarrhoeal controls, CDI was associated with more severe complaints, underlying diseases, antibiotic use and prior hospitalization. In our study, GPs requested a test for C. difficile in 7% of the stool samples, thereby detecting 40% of all CDIs. Dutch national recommendations advise testing for C. difficile when prior antibiotic use or hospitalization is present (18% of samples). If these recommendations were followed, 61% of all CDIs would have been detected. In conclusion, C. difficile is relatively frequent in general practice. Currently, testing for C. difficile is rare and only 40% of CDI in general practice is detected. Following recommendations that are based on traditional risk factors for CDI, would improve detection of CDI.     

产气荚膜梭菌群体感应系统研究进展北大核心CSCD

产气荚膜梭菌是一种分布广泛的条件致病菌,可以导致人与动物多种疾病,其中包括坏死性肠炎、气性坏疽、食物中毒等主要病症。群体感应是细菌之间一种重要的通讯机制,参与调节细菌毒素分泌和致病相关等重要过程。通过对产气荚膜梭菌的群体感应研究现状进行系统介绍,主要描述该菌所含群体感应系统的种类,各个群体感应与生物膜、毒素等致病相关表型的调控机制。产气荚膜梭菌已被证明具有两种群体感应系统,参与该菌毒素产生、生物被膜形成、孢子形成等致病性状。本研究进展为今后进一步研究产气荚膜梭菌致病相关机理提供一定理论基础,同时也为产气荚膜梭菌的生物防控提供新的思路。今后研究应绘制出产气荚膜梭菌完整的QS系统,进一步寻找安全有效的抗感染疗法。     

艰难梭菌毒素B诱导结肠癌细胞凋亡及相关机制研究

目的检测艰难梭菌毒素B(TcdB)对结肠癌SW480细胞增殖与凋亡的影响,研究其引起细胞凋亡的相关机制。方法采用不同浓度的TcdB处理SW480细胞,采用MTT法检测细胞增殖情况;用流式细胞术检测细胞的凋亡及线粒体膜电位变化情况。结果TcdB显著抑制了结肠癌SW480细胞的增殖,作用48 h后的抑制率为46.36%,呈一定的时间-浓度相关性;流式细胞仪检测结果表明,浓度为800 ng/ml的TcdB作用48 h,SW480细胞凋亡率为20.83%,呈一定的时间-浓度相关性。结论艰难梭菌毒素B能够抑制结肠癌SW480细胞增殖、诱导细胞凋亡,其机制可能与启动线粒体凋亡途径有关。     

A cohort study for the derivation and validation of a clinical prediction scale for hospital-onset Clostridium difficile infection

OBJECTIVE:

To develop and validate a clinical prediction scale for hospital-onset Clostridium difficile infection (CDI).

METHODS:

A community-based, 360-bed hospital located in the suburbs of a metropolitan area in the United States served as the setting for the present retrospective cohort study. The cohort consisted of patients admitted to the adult medical service over a six-year period from October 2005 to September 2011. The cohort was divided into derivation (October 2005 to September 2009) and validation (October 2009 to September 2011) groups. The primary outcome measure was hospital-onset CDIs identified as stool positive for C difficile after 48 h of hospital admission ordered for new-onset unformed stool by the treating physician.

RESULTS:

In the derivation phase, 35,588 patients were admitted to the medical service and 21,541 stayed in hospital beyond 48 h. A total of 266 cases of CDI were identified, 121 of which were hospital onset. The developed clinical prediction scale included the onset of unformed stool (5 points), length of hospital stay beyond seven days (4 points), age >65 years (3 points), long-term care facility residence (2 points), high-risk antibiotic use (1 point) and hypoalbuminemia (1 point). The scale had an area under the receiver operating curve (AUC) of 0.93 (95% CI 0.82 to 0.94) in predicting hospital-onset CDI, with a sensitivity of 0.94 (95% CI 0.88 to 0.97) and a specificity of 0.80 (95% CI 0.79 to 0.80) at a cut-off score of 9 on the scale. During the validation phase, 16,477 patients were admitted, of whom 10,793 stayed beyond 48 h and 58 acquired CDI during hospitalization. The predictive performance of the score was maintained in the validation cohort (AUC 0.95 [95% CI 0.93 to 0.96]) and the goodness-to-fit model demonstrated good calibration.

CONCLUSION:

The authors developed and validated a simple clinical prediction scale for hospital-onset CDI. This score can be used for periodical evaluation of hospitalized patients for early initiation of contact precautions and empirical treatment once it is validated externally in a prospective manner.     

A Canadian Working Group report on fecal microbial therapy: microbial ecosystems therapeutics

A working group from across Canada comprised of clinician and basic scientists, epidemiologists, ethicists, Health Canada regulatory authorities and representatives of major funding agencies (Canadian Institutes of Health Research and the Crohn's and Colitis Foundation of Canada) met to review the current experience with fecal microbial therapy and to identify the key areas of study required to move this field forward. The report highlights the promise of fecal microbial therapy and related synthetic stool therapy (together called 'microbial ecosystems therapeutics') for the treatment of Clostridium difficile colitis and, possibly, other disorders. It identifies pressing clinical issues that need to be addressed as well as social, ethical and regulatory barriers to the use of these important therapies.     

Clinical Predictors of Fulminant Colitis in Patients with Clostridium difficile Infection

Background/Aim:

Clostridium difficile infection (CDI) can affect up to 8% of hospitalized patients. Twenty-five percent CDI patients may develop C. difficile associated diarrhea (CDAD) and 1–3% may progress to fulminant C. difficile colitis (FCDC). Once developed, FCDC has higher rates of complications and mortality.

Patients and Methods:

A 10-year retrospective review of FCDC patients who underwent colectomy was performed and compared with randomly selected age- and sex-matched non-fulminant CDAD patients at our institution. FCDC (n=18) and CDAD (n=49) groups were defined clinically, radiologically, and pathologically. Univariate analysis was performed using Chi-square and Student''s t test followed by multivariate logistic regression to compute independent predictors.

Results:

FCDC patients were significantly older (77 ± 13 years), presented with triad of abdominal pain (89%), diarrhea (72%), and distention (39%); 28% had prior CDI and had greater hemodynamic instability. In contrast, CDAD patients were comparatively younger (65 ± 20 years), presented with only 1 or 2 of these 3 symptoms and only 5% had prior CDI. No significant difference was noted between the 2 groups in terms of comorbid conditions, use of antibiotics, or proton pump inhibitor. Leukocytosis was significantly higher in FCDC patients (18.6 ± 15.8/mm³ vs 10.7 ± 5.2/mm³; P=0.04) and further increased until the point of surgery. Use of antiperistaltic medications was higher in FCDC than CDAD group (56% vs 22%; P=0.01).

Conclusions:

Our data suggest several clinical and laboratory features in CDI patients, which may be indicative of FCDC. These include old age (>70 years), prior CDI, clinical triad of increasing abdominal pain, distention and diarrhea, profound leukocytosis (>18,000/mm³), hemodynamic instability, and use of antiperistaltic medications.     

Diagnostic accuracy of loop-mediated isothermal amplification in detection of Clostridium difficile in stool samples: a meta-analysis

Introduction

Clostridium difficile infection (CDI) remains a diagnostic challenge for clinicians. More recently, loop-mediated isothermal amplification (LAMP) has become readily available for the diagnosis of CDI, and many studies have investigated the usefulness of LAMP for rapid and accurate diagnosis of CDI. However, the overall diagnostic accuracy of LAMP for CDI remains unclear. In this meta-analysis, our aim was to establish the overall diagnostic accuracy of LAMP in detection of Clostridium difficile (CD) in stool samples.

Material and methods

A search was done in PubMed, MEDLINE, EMBASE and Cochrane Library databases up to February 2014 to identify published studies that evaluated the diagnostic role of LAMP for CD. Methodological quality was assessed according to the quality assessment for studies of diagnostic accuracy (QUADAS) instrument. The sensitivities (SEN), specificities (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were pooled statistically using random effects models. Statistical analysis was performed by employing Meta-Disc 1.4 software. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. Funnel plots were used to test the potential publication bias.

Result

A total of 9 studies met inclusion criteria for the present meta-analysis. The pooled SEN and SPE for diagnosing CD were 0.93 (95% CI: 0.91–0.95) and 0.98 (95% CI: 0.98–0.99), respectively. The PLR was 47.72 (95% CI: 15.10–150.82), NLR was 0.07 (95% CI: 0.04–0.14) and DOR was 745.19 (95% CI: 229.30−2421.72). The area under the ROC was 0.98. Meta-regression indicated that the total number of samples was a source of heterogeneity for LAMP in detection of CD. The funnel plots suggested no publication bias.

Conclusions

The LAMP meets the minimum desirable characteristics of a diagnostic test of SEN, SPE and other measures of accuracy in the diagnosis of CD, and it is suitable as a rapid, effective and reliable stand-alone diagnostic test for diagnosis of CDI, potentially decreasing morbidity and nosocomial spread of CD.     

How do Clostridium difficile infections affect nurses’ everyday hospital work: A qualitative study

This qualitative study explored the impact of Clostridium difficile infections on nurses’ everyday work in the hospital. Twelve nurses (six in France and six in the United States) were interviewed in depth using a semi‐structured interview guide. Thematic analysis of the interviews was performed. Managing diarrhoea and taking precautionary measures for infection control were the two most inconvenient aspects nurses reported with C. difficile patient management. Precautions included contact isolation, hand hygiene and reorganization/coordination of nursing care and ward. Precautions were time consuming and significantly increased nurses’ workload when combined with caring for patients with uncontrollable, frequent bouts of diarrhoea. Management of C. difficile infection is extremely burdensome for nurses in their everyday work and disruptive to hospital organizations as a whole. Prevention of C. difficile infections, together with coordinated team work and communication, would therefore contribute to decreasing nurses’ workload and the burden to health‐care facilities associated with caring for these patients.     

Inhibition of adhesion of Clostridium difficile to human intestinal cells after treatment with serum and intestinal fluid isolated from mice immunized with nontoxigenic C. difficile membrane fraction

Diarrhea and pseudomembrane colitis caused by Clostridium difficile infection is a global health concern because of the high recurrence rate after standard antibiotic therapy. Vaccination presents a powerful countermeasure against disease recurrence. In this study, mice vaccinated with the nontoxigenic C. difficile membrane fraction generated a marked immune response to the antigen, as demonstrated by the serum IgG and intestinal fluid IgA levels. Significantly, pretreatment with harvested IgG- and IgA-containing fluids was sufficient to prevent in vitro adhesion of C. difficile to human Caco-2 intestinal cells. These results highlight the potential of nontoxigenic C. difficile membrane fraction as a vaccine candidate for C. difficile infection.