Transmission of Clostridium difficile spores in isolation room environments and through hospital beds

The aim of this study was to determine the dissemination of Clostridium difficile (CD) spores in a hospital setting where the potassium monopersulfate‐based disinfectant Virkon^TM was used for cleaning. In the initial part of the study, we sampled 16 areas of frequent patient contact in 10 patient rooms where a patient with CD infection (CDI) had been accommodated. In the second part of the study, we obtained samples from 10 patient beds after discharge of CDI patients, both before and after the beds were cleaned. In the first part, CDspores were isolated in only 30% of the rooms. In the second part, which focused on transmission to hospital beds, C. difficile was found in four of 10 beds either before or after cleaning. In conclusion, in both parts of the study, we demonstrated a moderate spread of CD spores to the environment despite routine cleaning procedures involving Virkon^TM.     

Veal Calves Produce Less Antibodies against C. Perfringens Alpha Toxin Compared to Beef Calves

Enterotoxaemia is a disease with a high associated mortality rate, affecting beef and veal calves worldwide, caused by C. perfringens alpha toxin and perfringolysin. A longitudinal study was conducted to determine the dynamics of antibodies against these toxins in 528 calves on 4 beef and 15 veal farms. The second study aimed to determine the effect of solid feed intake on the production of antibodies against alpha toxin and perfringolysin. The control group only received milk replacer, whereas in the test group solid feed was provided. Maternal antibodies for alpha toxin were present in 45% of the veal calves and 66% of the beef calves. In beef calves a fluent transition from maternal to active immunity was observed for alpha toxin, whereas almost no veal calves developed active immunity. Perfringolysin antibodies significantly declined both in veal and beef calves. In the second study all calves were seropositive for alpha toxin throughout the experiment and solid feed intake did not alter the dynamics of alpha and perfringolysin antibodies. In conclusion, the present study showed that veal calves on a traditional milk replacer diet had significantly lower alpha toxin antibodies compared to beef calves in the risk period for enterotoxaemia, whereas no differences were noticed for perfringolysin.     

Microbiologic factors affecting Clostridium difficile recurrence

BackgroundRecurrent Clostridium difficile infection (rCDI) places a huge economic and practical burden on healthcare facilities. Furthermore, rCDI may affect quality of life, leaving patients in an rCDI cycle and dependant on antibiotic therapy.AimsTo discuss the importance of microbiologic factors in the development of rCDI.SourcesLiterature was drawn from a search of PubMed from 2000 onwards with the search term ‘recurrent Clostridium difficile infection’ and further references cited within these articles.ContentMeta-analyses and systematic reviews have shown that CDI and rCDI risk factors are similar. Development of rCDI is attendant on many factors, including immune status or function, comorbidities and concomitant treatments. Studies suggest that poor bacterial diversity is correlated with clinical rCDI. Narrow-spectrum gut microflora-sparing antimicrobials (e.g. surotomycin, cadazolid, ridinilazole) are in development for CDI treatment, while microbiota therapeutics (faecal microbiota transplantation, nontoxigenic C. difficile, stool substitutes) are increasingly being explored. rCDI can only occur when viable C. difficile spores are present, either within the gut lumen after infection or when reacquired from the environment. C. difficile spore germination can be influenced by gut environmental factors resulting from dysbiosis, and spore outgrowth may be affected stage by some antimicrobials (e.g. fidaxomicin, ramoplanin, oritavancin).ImplicationsrCDI is a significant challenge for healthcare professionals, requiring a multifaceted approach; optimized infection control to minimize reinfection; C. difficile–targeted antibiotics to minimize dysbiosis; and gut microflora restoration to promote colonization resistance. These elements should be informed by our understanding of the microbiologic factors involved in both C. difficile itself and the gut microbiome.     

A contemporary review of Clostridioides difficile infections in patients with haematologic diseases

Clostridioides (Clostridium) difficile (C. difficile) infection is one of the most common causes of increased morbidity and mortality. Approximately 500 000 C. difficile infections (CDIs) occur each year in the United States, and they result in more than 29 000 deaths. Patients with haematologic diseases are at a higher risk for this infection due to frequent hospitalization and exposure to treatment-associated risk factors. Whilst several currently available antimicrobial agents offer resolution, recurrence of infection remains a major concern. Recent advancement in deciphering C. difficile virulence mechanisms and identification of its allies in contributing to the infection has led to the development of alternative treatment strategies. Here, we will provide a contemporary discussion of how major risk factors in haematologic diseases, such as immunosuppression, chemoradiation, use of antibiotic, proton pump inhibitor and opioid, and deficiency in butyrate and antimicrobial peptides contribute to C. difficile infection. Next, we will highlight different approaches to control and mitigate this infection such as antibiotic stewardship and faecal microbiota transplantation. Finally, we will explore several emerging treatments such as use of pre- and probiotics, immunotherapy and microbiome-sparing agents.     

Immunological mechanisms of fecal microbiota transplantation in recurrent Clostridioides difficile infection

Fecal microbiota transplantation (FMT) is a successful method for treating recurrent Clostridioides difficile (C. difficile) infection (rCDI) with around 90% efficacy. Due to the relative simplicity of this approach, it is being widely used and currently, thousands of patients have been treated with FMT worldwide. Nonetheless, the mechanisms underlying its effects are just beginning to be understood. Data indicate that FMT effectiveness is due to a combination of microbiological direct mechanisms against C. difficile, but also through indirect mechanisms including the production of microbiota-derived metabolites as secondary bile acids and short chain fatty acids. Moreover, the modulation of the strong inflammatory response triggered by C. difficile after FMT seems to rely on a pivotal role of regulatory T cells, which would be responsible for the reduction of several cells and soluble inflammatory mediators, ensuing normalization of the intestinal mucosal immune system. In this minireview, we analyze recent advances in these immunological aspects associated with the efficacy of FMT.     

The roles of toxin A and toxin B in Clostridium difficile infection

We recently published our findings indicating that anti-TcdB antibodies were effective as treatment for C. difficile infection, but that anti-TcdA actually worsened prognosis in the gnotobiotic piglet model. To further investigate the roles of the two toxins, we administered purified toxins separately or together, systemically, to piglets and found that both toxins, either alone or together, are able to elicit severe lesions systemically and are also able to cross into the gut lumen and cause large intestinal lesions typical of infection. We also found that anti-TcdA administered before systemic challenge with TcdA again did not protect from development of disease, but, in this case, did not appear to worsen prognosis. Further work is still needed, but these findings add to the growing knowledge regarding the roles of the C. difficile toxins.