Clostridium Difficile Pathogenicity Mechanism Associated with Dysbiosis Caused by The Use of Antibacterials

Clostridium difficile is a gram-positive rod responsible for the majority of hospital-acquired gastrointestinal infections in humans. Recently in the world literature an exponential increase in its incidence has been reported, involving new more virulent strains that affect new groups of patients that were previously unaffected, generating a series of changes in the clinical presentation of the disease and in the treatment, which influ- ences the prognosis of the disease in these patients. An early diagnosis is essential for therapeutic management and for the implementation of con-tainment measures. However, the speed with which new strains with greater pathogenicity are developed is higher than that with which new drugs are developed to combat them, all this as a result of the irrational use of antibiotics that alter the pathogenicity mechanism of this type of bacteria. In this article we review the pathophysiological aspects of C. difficile infection associated with dysbiosis caused by the use of antibacterials, with the aim of contributing to the preparation of general practitioners and specialists to provide timely and quality care to those who receive it. suffer from this disease and make a more rational use of antibiotics.

of C. difficile infection, although theoretically any antibiotic is a potential risk factor for developing it. It affects up to around 10% of hospitalized patients and is the most common cause of nosocomial diarrhea globally. It is the causative agent in 20-30% of cases of diarrhea associated with the use of antibiotics, 60-80% of colitis associated with the use of antibiotics, and 80-100% of episodes of pseudomembranous colitis associated with antibiotics [3].

Materials and Methods
A narrative review was carried out, in which the PubMed, Scielo and ScienceDirect databases, among others, were searched.
The collection and selection of articles was carried out in journals indexed in first and second languages from 2012 to 2020. As keywords, the following terms were used in the databases according to the DeCS and MeSH methodology: Clostridium difficile, Dysbiosis, Antibiotics In this review, 40 original and review publications related to the subject studied were identified, of which 15 articles met the specified inclusion requirements, such as articles that were in a range not less than the year 2012, which were articles of full text and to report on the pathogenicity mechanism of clostridium difficile and its association with dysbiosis caused by the use of antibacterials, as exclusion criteria it was taken into account that the articles did not have sufficient information and that they did not present the full text to the time of review.

Results
Antibiotics are often widely used today, in the face of gastrointestinal infections they play a very important role as a therapy to eradicate pathogenic microorganisms and their use can even be seen in prophylactic treatments, but many times their use can affect the health of the patients. people, causing unwanted adverse effects, diarrhea is one of the most common complications associated with the use of these, with most of these dysenteric pictures related to infections by c. difficille [4].
Historically, in the decade of the 70s, a significant number of diarrhea and colitis associated with the use of antibiotics to treat different infections of gastrointestinal origin began to appear, somehow it was found that in those patients who received treatment with clindamycin the picture was more noticeable. Studying this fact, it was found that around 21% of the patients receiving clindamycin Once germinated, C. difficile produces two toxins, toxin A and toxin B, in addition to a binary toxin. These toxins are responsible for the pathogenesis of C. difficile, so only strains of C. difficile that can produce at least 1 of these 2 toxins can cause disease. These toxins are encoded by two different genes (tcdA and tcdB) that are found at the same pathogenicity locus (PaLoc). At this locus there are also three more genes that have the function of regulating the production of these toxins (tcdC, tcdR and tcdE). The tcdE gene codes for a holin in charge of making pores in the cytoplasmic membrane so that toxins can be released, while the tcdC and tcdR genes are the negative and positive regulators, respectively, of the production of these toxins [11].
On the other hand, the binary toxin is not encoded in this locus, which is why it induces the formation of protrusions in the microtubules of the cells, which increases the adherence of the bacteria to the intestinal epithelium, this is how the infestation occurs. by C. difficile when the natural microbiota is altered by the use of antibiotics [12].

Discussion
The results of various studies support what is stated in this document, about the existence of a relationship between inhospital treatment with antibiotics and the appearance of C. difficile infections, due to the fact that antibiotics alter the intestinal microbiota causing dysbiosis, facilitating the establishment of this infectious process, as we have discussed throughout this article, the incidence of community-acquired C. difficile infections is considerably low compared to confirmed positive cases in the hospital, it has been reported that community-acquired infection occurs in young patients, generally with immunosuppression and without previous antibiotic therapy [13]. Regarding the role that antibiotics play in this disease, previous studies suggest that the frequency and recurrence of infection due to the use of antibiotics is the same, regardless of whether it is treated with vancomycin or metronidazole, however, the risk of developing complications it is slightly higher if vancomycin is used.
One of the factors that could be influencing within the hospital area is the lack of isolation, any patient with suspected C. difficile infection should be placed in an individual room to avoid the spread of spores, therefore, if we group the use antibiotics, exposure and contact with the infectious agent, we will surely have a C.
difficile infection [14]. In conclusion, the present work shows the pathogenicity mechanism of clostridium difficile associated with dysbiosis caused by the use of antibacterials. For which we suggest the prophylactic and concomitant use of probiotics together with antibiotic therapy to avoid intestinal dysbiosis and reduce the risk of developing C. difficile infection, especially in the hospital area. It should be noted that the use of probiotics in patients with established C. difficile infection is not recommended [15].