NAAT, like a standalone test, is not appropriate to provide an adequate clinical positive predictive value (PPV) with low CDI prevalence . antibodies, vaccines and fresh molecules, already developed or in the pipeline. However, the Dryocrassin ABBA management of CDI recurrences and severe infections remain demanding and the main question remains: how to best target these often expensive treatments to the right population. With this review we discuss current diagnostic methods, treatment and potential prevention strategies, with a special focus on recent improvements in the field as well as areas of uncertainty and unmet needs and how to address them. (formerly is a major cause of healthcare-associated diarrhea, and is progressively present in the community. A lot offers changed in our understanding of the physiopathology of this frequent pathogen as well as with the analysis and treatment of illness (CDI). However, several questions remain unanswered. Diagnostic methods and monitoring systems vary substantially between areas hindering an accurate estimation of the global burden of CDI. Furthermore, analysis remains suboptimal, especially in certain settings, such as the community. The management of recurrences, severe and complicated disease, and the optimal use of fresh therapeutic molecules to target the Dryocrassin ABBA right human population remain demanding. Finally, areas of uncertainty persist regarding the significance of asymptomatic carriage, the optimal medical endpoints and the long-term follow-up and results of these individuals. We selected a number of publications by searching into Pubmed to review the epidemiology, clinical presentation, results and management of CDI. We discuss current diagnostic methods and treatment options, with a special focus on areas of uncertainty and recent improvements in the field. 2. Epidemiology The incidence of illness markedly improved worldwide in the 2000s [1,2,3], in part due to the emergence and quick spread throughout North America and Europe of the virulent, epidemic ribotype 027 strain (North-American Pulsefield type 1, NAP1/027), which was associated with improved severity of disease and mortality [4,5,6]. At the same time, the intro of more sensitive Dryocrassin ABBA diagnostic assays, such as nucleic acid amplification assays (NAAT), seems to have contributed to a substantial increase in the reported CDI incidence [7,8]. Further adding to an already high burden, recurrences after analysis of CDI are frequent, with 10C30% of individuals developing at least one recurrence and the risk increasing with each successive show [9,10]. To be MAPK3 able to accurately evaluate the burden of CDI, there is a need for standardization of diagnostic algorithms and a powerful surveillance system, and this need is not entirely nor universally met. In the US, an estimated 453,000 instances of infection occurred in 2011 based on data from active human population- and laboratory-based monitoring across different geographic areas, resulting in approximately 29,000 deaths . On a more positive note, relating to a more recent study by Guh et al., the estimated burden of CDI decreased in the US between 2011 and 2017, probably as a result of improved illness control actions and a concomitant overall decrease of healthcare-associated infections (HAIs) . Epidemiological data are scarcer in Europe. The lack of a standardization of diagnostic methods in hospitals, as well as the heterogeneity in the presence and the strategy of national monitoring and the availability of molecular typing, hinder a more accurate overview of the burden of CDI. In a study carried out in 34 European countries in 2008, the incidence and distribution of causative ribotypes assorted greatly between countries, with an overall incidence of 4.1 per 10,000 patient-days per hospital . was the sixth most frequent pathogen responsible for healthcare-associated infections inside a Western point prevalence study carried out in 2016C2017, with an annual estimated number of cases of 189,256 . Continued molecular typing is also important for a better understanding of the current epidemiology as well as in order to timely detect growing strains. For instance, even though the prevalence of 027 ribotype is definitely decreasing in Europe [1,13], the emergence of a virulent strain ribotype 078 has been reported in the Netherlands, with an increasing prevalence between 2005 and 2008 and a severity similar to that reported with ribotype 027 . The unmet demands in epidemiology are summarized in Package 1. Package 1 Unmet Needs in Epidemiology. Despite the important burden of CDI, diagnostic methods and monitoring vary across areas and countries in Europe, hampering a global and more exact overview of the burden of CDI. There is an urgent need to obtain Western data on CDI burden in private hospitals and in the community. 3. Analysis and Microbiology Despite the great progress in diagnostic methods and the availability of.