Relationship Between C. Difficile Toxins' Serum Level With C. Difficile Infection
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 45
- 主要终点
- Correlation of toxins kinetics and CDI severity
研究概览
简要总结
To assess the association between Clostridium difficile (CD) toxins' serum levels and the grade of Clostridium difficile infection (CDI) severity/failure to CDI treatment and rate of recurrence. Furthermore, the kinetics of CD toxins in serum of CDI patients undergoing anti-CDI treatment, as well as the relationship between serum toxins levels and length of CDI diarrhea will be evaluated.
详细描述
Background. C. difficile frequently induces toxemia, however due to limited sensitivity of existing diagnostic tools, it goes undetected in common clinical practice. Although undetected, Clostridium difficile infection (CDI)-induced toxemia is often experienced, and this explains the systemic complications of life-threatening CDI cases. Until recently, although the pathogenetic process was already known, the phenomenon of extraintestinal damage caused by C. difficile toxins has been undervalued. However, a recent study has proven toxemia in humans. In the last 5 years, animal studies have proven the presence of C. difficile toxins in several body fluids, toxemia correlating with systemic disease and mortality. However, although toxin A (TcdA) and B (TcdB) are the primary virulence factors responsible for C. difficile-associated diarrhea and inflammation, only three toxemia-positive cases (two adults and one child) have been reported so far in humans. The explanation for such a low number of toxemia-positive cases may be the lack of sensitive toxins detection method.
Objectives.
- To assess the association between CD toxins' serum levels and grade of CDI severity/failure to CDI treatment and rate of recurrence.
- To evaluate the kinetics of CD toxins in serum of CDI patients undergoing anti-CDI treatment.
- To assess the relationship between serum toxins levels and length of CDI diarrhoea.
Study design. Prospective observational study on the measurement of serum levels of CD toxins in patients with CDI.
In order to assess the relationship between C difficile toxins' serum level and severity and recurrence rate, 45 consecutive patients with documented CDI infection will be studied, including 20 with mild-moderate CDI, 20 with severe CDI, and 5 with severe complicated/fulminant CDI according to ESCMID definition. For each patient three determination of serum toxins will be performed at time 0 (before initiation of anti-CDI treatment), 4d, 10d.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •45 consecutive patients with documented CDI infection, including:
- •20 with mild-moderate CDI
- •20 with severe CDI
- •5 with severe complicated/fulminant CDI, according to ESCMID definition.
排除标准
- 未提供
结局指标
主要结局
Correlation of toxins kinetics and CDI severity
时间窗: Determination of serum toxin kinetics will be evaluated by the change from baseline levels (time 0) at 4 and 10 days from the initiation of anti-CDI treatment. For recurrence rate, the follow up will be of 30 days after cessation of diarrhea.
Toxin kinetics (TcdA alone, TcdB alone, TcdA+TcdB) will be correlated by one-way analysis of variance (ANOVA) with CDI severity (defined according to ESCMID guidelines)
Validation on the proposed method
时间窗: The proposed method will be compared with reference tests evaluating change of serum toxins levels after 4 and 10 days from the initiation of anti-CDI treatment with levels before initiation of anti-CDI treatment.
According to ESCMID guidelines, our method will be compared with reference tests that are defined as the best tests currently available for CDI diagnosis (i.e., cell cytotoxicity neutralization assay (CCNA) and toxigenic culture (TC)). As both these reference tests detect different things, and because of this they will not necessarily agree with each other in all samples, results for each reference test will be analysed separately.
Correlation between toxins levels and the recurrence rate
时间窗: Determination of serum toxin kinetics will be evaluated by the change from baseline levels (time 0) at 30 days from the cessation of diarrhea.
Toxin kinetics (TcdA alone, TcdB alone, TcdA+TcdB) will be correlated with the recurrence rate. A multivariate logistic regression model will be used to assess predictors of poor outcome of CDI. The odds ratio (OR) and 95% confidence interval (CI) will be calculated. The Spearman correlation coefficients and Wilcoxon rank sum tests will be used to determine whether TcdA and TcdB levels could be associated with the recurrence rate.
Performance of the proposed method
时间窗: The evaluation of the performance of the proposed method will be assed by evaluating the change of toxins levels from baseline levels (time 0) at 4 and 10 days from the initiation of anti-CDI treatment.
The performance of our method will be assessed using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the prediction rule of poor outcome will be calculated. Validity values will be calculated with a 95% CI following an exact binomial distribution. A P value \<0.05 will be considered significant
Correlation between toxins levels and the duration of diarrhea
时间窗: Determination of serum toxin kinetics will be evaluated by the change from baseline levels (time 0) at 4 and 10 days from the initiation of anti-CDI treatment.
Toxin kinetics (TcdA alone, TcdB alone, TcdA+TcdB) will be correlated with the duration of diarrhea. A multivariate logistic regression model will be used. The odds ratio (OR) and 95% confidence interval (CI) will be calculated. The Spearman correlation coefficients and Wilcoxon rank sum tests will be used to determine whether TcdA and TcdB levels could be associated with the duration of diarrhea.
Correlation between toxins levels and mortality rate
时间窗: Time-to-Event measure: toxin levels versus mortality rate, from date of patient enrollment to the date of death from any cause assessed up to 12 months.
Survival curves comparing the mortality with toxin(s) levels will be calculated using the Kaplan-Meier method and tested for significance using the log-rank test. P\<0.05 will be considered statistically significant.
Setup of the method.
时间窗: For each patient, the change of serum toxins levels after 4 and 10 days from the initation of anti-CDI treatment will be compared to levels before initation of anti-CDI treatment.
Mann-Whitney U-tests will be used to compare the intensity of each triplicate chemiluminescent spot of the CDI serum tested with the TcdA and TcdB standard curves, and to compare the intensities of the chemiluminescent spots of CDI patients with those of normal subjects. Quantitative variables will be expressed as the median and IQR.
次要结局
未报告次要终点