Intubation difficile : il faut suivre les recommandations

Intubation and ventilation impossible mask is a dramatic situation with potentially serious consequences. We report the case of a patient of 43 years, followed for a goiter, which was scheduled for a total thyroidectomy under general anesthesia. Preoperative evaluation is not noted signs of compression or tracheal deviation, and there were no criteria predictive of intubation or difficult mask ventilation. The induction of anesthesia was standard. Mask ventilation was effective allowing paralysis. The standard laryngoscopy showed a score of Cormack and Lehane grade IV. Several attempts at intubation were made leading to a situation of intubation and ventilation impossible mask with deep desaturation. A tracheostomy was done urgently. The patient was operated on, six months later, with a fiber optic intubation. Through this case, the authors draw attention to the difficulty of achieving an emergency tracheotomy in the presence of goiter and emphasize the need for integration of different modes of learning and retention of management skills of the upper airway.     

抗艰难梭菌rakicidin B1新衍生物的设计、合成及生物学活性评价

目的 以rakicidin B1为起始原料,经2步反应合成得到4个全新结构的rakicidin B1衍生物,并对其进行生物学活性研究,以期获得低细胞毒、高效抗艰难梭菌活性的化合物。方法 课题组前期首次发现rakicidin B1具有较强的抗艰难梭菌活性,在其结构基础上进行修饰和优化,通过氨基甲酸酯连接基团引入含氮杂环,设计合成得到4个全新目标化合物。所有化合物结构经高分辩质谱和核磁确证,并经抗艰难梭菌活性测试和细胞毒性活性测试。结果 在合成的4个化合物中,有3个化合物具有与先导化合物更强或相当的抗艰难梭菌活性;同时,MTT测试结果表明,3个化合物的细胞毒性降低,以3b的细胞毒性降低最多。结论 通过对rakicidin B1母核结构进行修饰和优化,获得全新结构的rakicidin B1衍生物并对其进行抗菌和细胞毒活性筛选。其中,化合物3b保留潜在抗艰难梭菌活性且细胞毒性降低最多,作为全新结构类型的抗艰难梭菌活性化合物,有潜在的开发价值。     

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。     

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.     

Antimicrobial stewardship in daily practice: Managing an important resource

Antimicrobial stewardship is a recent concept that embodies the practical, judicious use of antimicrobials to decrease adverse outcomes from antimicrobials while optimizing the treatment of bacterial infections to reduce the emergence of resistant pathogens. The objectives of the present statement are to illustrate the principles of antimicrobial stewardship and to offer practical examples of how to make antimicrobial stewardship part of everyday hospital and outpatient practice. Vital components of antimicrobial stewardship include appropriate testing to diagnose whether infections are viral or bacterial, and using clinical follow-up rather than antibiotics in cases in which the child is not very ill and uncertainty exists. Other specific, important actions include questioning whether positive urine cultures are contaminated when there is no evidence of pyuria or inflammatory changes, and obtaining a chest radiograph to support a diagnosis of bacterial pneumonia. Optimizing the choice and dosage of antimicrobials also reduces the probability of clinical failures and subsequent courses of antimicrobials. A list of common clinical scenarios to promote stew-ardship is included.     

A Highly Specific Holin-Mediated Mechanism Facilitates the Secretion of Lethal Toxin TcsL in Paeniclostridium sordellii

Protein secretion is generally mediated by a series of distinct pathways in bacteria. Recently, evidence of a novel bacterial secretion pathway involving a bacteriophage-related protein has emerged. TcdE, a holin-like protein encoded by toxigenic isolates of Clostridioides difficile, mediates the release of the large clostridial glucosylating toxins (LCGTs), TcdA and TcdB, and TpeL from C. perfringens uses another holin-like protein, TpeE, for its secretion; however, it is not yet known if TcdE or TpeE secretion is specific to these proteins. It is also unknown if other members of the LCGT-producing clostridia, including Paeniclostridium sordellii (previously Clostridium sordellii), use a similar toxin-release mechanism. Here, we confirm that each of the LCGT-producing clostridia encode functional holin-like proteins in close proximity to the toxin genes. To characterise the respective roles of these holin-like proteins in the release of the LCGTs, P. sordellii and its lethal toxin, TcsL, were used as a model. Construction and analysis of mutants of the P. sordellii tcsE (holin-like) gene demonstrated that TcsE plays a significant role in TcsL release. Proteomic analysis of the secretome from the tcsE mutant confirmed that TcsE is required for efficient TcsL secretion. Unexpectedly, comparative sample analysis showed that TcsL was the only protein significantly altered in its release, suggesting that this holin-like protein has specifically evolved to function in the release of this important virulence factor. This specificity has, to our knowledge, not been previously shown and suggests that this protein may function as part of a specific mechanism for the release of all LCGTs.     

Vitamin D supplementation in pregnancy and early infancy in relation to gut microbiota composition and C. difficile colonization: implications for viral respiratory infections

ABSTRACT

In Canada and the US, the infant diet is supplemented with vitamin D via supplement drops or formula. Pregnant and nursing mothers often take vitamin D supplements. Since little is known about the impact of this supplementation on infant gut microbiota, we undertook a study to determine the association between maternal and infant vitamin D supplementation, infant gut microbiota composition and Clostridioides difficile colonization in 1,157 mother-infant pairs of the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study over 2009–2012. Logistic and MaAsLin regression were employed to assess associations between vitamin D supplementation, and C. difficile colonization, or other gut microbiota, respectively. Sixty-five percent of infants received a vitamin D supplement. Among all infants, infant vitamin D supplementation was associated with a lower abundance of genus Megamonas (q = 0.01) in gut microbiota. Among those exclusively breastfed, maternal prenatal supplementation was associated with lower abundance of Bilophila (q = 0.01) and of Lachnospiraceae (q = 0.02) but higher abundance of Haemophilus (q = 0.02). There were no differences in microbiota composition with vitamin D supplementation among partially and not breastfed infants. Neither infant nor maternal vitamin D supplementation were associated with C. difficile colonization, after adjusting for breastfeeding status and other factors. However, maternal consumption of vitamin-D fortified milk reduced the likelihood of C. difficile colonization in infants (adjustedOR: 0.40, 95% CI: 0.19–0.82). The impact of this compositional difference on later childhood health, especially defense against viral respiratory infection, may go beyond the expected effects of vitamin D supplements and remains to be ascertained.