PROSPECTIVE STUDY OF PREDISPOSING FACTORS OF REFRACTARY Clostridium Difficile INFECTION. INFLUENCE OF THE GUT MICROBIOMA

Overview

A higher frequency of recurrences in the University Hospital of Cabueñes (HUCAB) than in other hospitals in our area, including Central University Hospital of Asturias (HUCA) has been found. This increase does not seem to be related to underlying diseases, age, sex or predisposing factors classically described in this type of infection. This high rate of recurrence, together with the absence of response to all conventionally used antibiotic treatments, has important repercussions in the morbidity and mortality of patients, in the ecology of the hospital due to the risk of transmission of a strain of major severity and in the high costs associated with an increase in the hospitalization days of these patients, as well as in an eventual transfer of these to other structures specialized in fecal transplantation. Two hypotheses are proposed to explain the higher frequency reported: Hypothesis 1. There are alterations of the microbiome in patients with severe recurrences that favor the appearance of these. Hypothesis 2. The circulating strain in the hospital has intrinsic characteristics that make it more virulent, such as the presence of virulence or multiresistance factors. For this reason we design a descriptive, prospective multicentric study that will include all patients older than 18 years diagnosed with C difficile infection at the Central University Hospital of Asturias and the University Hospital of Cabueñes during the year 2020-2021

Clostridium difficile infection (CDI) is currently a priority public health problem. In recent decades, the exponential increase in the incidence and severity of CDI has forced to develop new and better methods of treatment and control of the infection. Currently, it is the most common cause of nosocomial infectious diarrhea, with 20 cases per 100,000 people / year or 15 cases per 1000 hospital discharges. The identification of risk factors for the CDI has become one of the basic pillars to study in order to improve epidemiological control. Classically known risk factors associated with CDI (hospitalization, advanced age, antibiotic prescription, gastrointestinal surgery) have joined in recent years as a result of recent research (for example, the use of proton pump inhibitors). One of the main problems offered by the management of the CDI is the role of recurrences. There is no consensus about the definition of recurrence in the international CDI management guidelines, however, it is usually established as the presence of diarrhea in the 30 days after an CDI that had presented positive toxin. The recurrence of the CDI implies a new level of complexity when dealing with the management of this infection: the recurrence percentages range between 15-50% after an initial episode, establishing in recent studies that it could be reasonable to estimate that 20-25% of the patients will present a recurrence in the first 30 days after finishing the antibiotic treatment for the CDI. In addition, after the first recurrence the risk of presenting a new one increases up to 45%, and the risk of subsequent recurrences doubles after 2 or more recurrences. The study of recurrence in the CDI is the objective of multiple studies. Its importance is based on both epidemiological and economic reasons, since each episode of recurrence increases hospital costs (in a study carried out by the Spanish Ministry of Health in 2013, it was estimated that each new episode of recurrence entailed an increase in the cost of 1000 euros) The new lines of recurrence research in CDI try to find associations between severity, microbiome, demographic findings and new risk factors and the possibility of recurrence, in order to try to predict it by developing clinical models predictive of recurrence, which, until now, they only have a very limited role. Previous data collected by our working group show important differences in the behavior of Clostridium difficile infection between the Central University Hospital of Asturias (HUCA) and the University Hospital of Cabueñes (HUCAB), among which the high number of recurrences and failures to conventional treatments in the latter, being necessary even fecal transplantation as a last therapeutic resource. In 2017, there were 27 patients with Clostridium difficile infection in the HUCAB, of whom 8 (33.3%) relapsed. In 2018, 4 (22.2%) of 18 patients relapsed, three of them more than three times. Analyzing the characteristics of patients with recurrence within the HUCAB during the years 2017-2018, we found that recurrences are significantly more frequent in patients treated with metronidazole, although this is possibly due to the fact that it is the drug used systematically as the first choice, and diagnosed with hepatopathy without differences between the other treatments, which supports the hypothesis that the differences are due more to the behavior of the strain than to the clinical characteristics of the patients. A higher frequency of recurrences in the University Hospital of Cabueñes (HUCAB) than in other hospitals in our area, including Central University Hospital of Asturias (HUCA) has been found. This increase does not seem to be related to underlying diseases, age, sex or predisposing factors classically described in this type of infection. This high rate of recurrence, together with the absence of response to all conventionally used antibiotic treatments, has important repercussions in the morbidity and mortality of patients, in the ecology of the hospital due to the risk of transmission of a strain of major severity and in the high costs associated with an increase in the hospitalization days of these patients, as well as in an eventual transfer of these to other structures specialized in fecal transplantation. Two hypotheses are proposed to explain the higher frequency reported: Hypothesis 1. There are alterations of the microbiome in patients with severe recurrences that favor the appearance of these. Hypothesis 2. The circulating strain in the hospital has intrinsic characteristics that make it more virulent, such as the presence of virulence or multiresistance factors We design a descriptive, prospective multicentric study that will include all patients older than 18 years diagnosed with C difficile infection at the Central University Hospital of Asturias and the University Hospital of Cabueñes during the year 2020-2021