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Original article
Case-control study of Clostridioides difficile in a rural health care area
Estudio de casos-controles de la infección por Clostridioides difficile en un área sanitaria rural
Cristina Muñoz Cuevasa, María Ángeles Asencio Egeaa,
Corresponding author
marian_asencio@yahoo.es

Corresponding author.
, María Franco Huertab, María Huertas Vaqueroa, Ángel Arias Ariasc, Rafael Carranza Gonzáleza
a Laboratorio de Microbiología, Hospital General La Mancha Centro, Ciudad Real, Spain
b Servicio de Medicina Interna, Hospital General La Mancha Centro, Ciudad Real, Spain
c Unidad de Apoyo a la Investigación, Hospital General La Mancha Centro, Ciudad Real, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Clostridioides difficile</span> is a global public health problem&#44; with <span class="elsevierStyleItalic">C</span>&#46; <span class="elsevierStyleItalic">difficile</span> infection &#40;CDI&#41; being the main cause of nosocomial diarrhoea in industrialised countries<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and the origin of an increasing number of cases of diarrhoea in the community&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> It can cause conditions ranging from moderate diarrhoea to pseudomembranous colitis and severe complications&#44; such as paralytic ileus and toxic megacolon&#46; A lack of clinical suspicion&#44; especially in those patients who do not exhibit the classic risk factors &#40;advanced age&#44; prolonged hospitalisation&#44; previous use of antibiotics&#41;&#44; means that CDI is still an underdiagnosed disease&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> This factor&#44; together with its morbidity and mortality&#44; raises the need for epidemiological studies to establish improved infection prevention and control strategies&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The aim of this study was to identify both the risk factors and prognostic factors for CDI in a rural health area&#44; as well as to establish the main differences between nosocomial and community cases&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Design</span><p id="par0015" class="elsevierStylePara elsevierViewall">This was an observational&#44; prospective&#44; case-control study of patients 2 years of age or over with diarrhoea &#40;&#8805;3 loose stools per day&#41; treated in the La Mancha Centro Health Area&#44; which serves a population of approximately 230&#44;000 inhabitants&#44; from 1 April 2015 to 30 May 2016&#46; The patient follow-up period was extended for two more months&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patient selection</span><p id="par0020" class="elsevierStylePara elsevierViewall">Case definition&#58; patient with a clinical and microbiological diagnosis of CDI treated in our health area&#46; Hospital case&#58; patient with CDI and hospital admission in the four weeks prior to infection&#44; or whose infection developed when they had been hospitalised for more than 48<span class="elsevierStyleHsp" style=""></span>h&#46; Community case &#40;CCDI&#41;&#58; patient with CDI without hospital admission in the previous four weeks&#44; or whose infection developed in the first 48<span class="elsevierStyleHsp" style=""></span>h after admission&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Control definition&#58; patient treated in our health area in the same period as the index case in which a stool culture was requested and the toxin test was negative&#46; They were considered a hospital control if they had also been admitted in the previous four weeks&#44; otherwise they were deemed a community control&#46; The controls chosen were patients who were closest in time and age to the index case&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Sample size</span><p id="par0030" class="elsevierStylePara elsevierViewall">All loose stools from patients aged 2 years or older received by the microbiology laboratory during the study period were consecutively included&#44; regardless of the clinician&#39;s request&#46; Number of cases&#58; 61 &#40;there were three cases that were ultimately excluded from the study because they were recurrences rather than new cases&#41;&#46; Number of controls&#58; 64&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Variables collected</span><p id="par0235" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#9633;</span><p id="par0035" class="elsevierStylePara elsevierViewall">Age&#44; gender&#44; acquisition &#40;community&#47;nosocomial&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#9633;</span><p id="par0040" class="elsevierStylePara elsevierViewall">Short-form Charlson Index&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> which includes cerebrovascular disease&#44; diabetes&#44; chronic obstructive pulmonary disease&#44; heart failure&#47;ischaemic heart disease&#44; dementia&#44; peripheral arterial disease&#44; chronic kidney disease and cancer&#46; In addition&#44; the following comorbidities were collected&#58; inflammatory bowel disease&#44; immunosuppression&#44; chemotherapy drugs&#44; solid-organ and&#47;or haematopoietic stem cell transplantation and hypoalbuminaemia&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#9633;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Symptoms&#58; fever associated with diarrhoea &#40;FAD&#41;&#44; diarrhoea&#44; abdominal pain and vomiting&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#9633;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Type of antibiotic&#44; antacid or immunosuppressant previously administered&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#9633;</span><p id="par0055" class="elsevierStylePara elsevierViewall">CDI type&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">o</span><p id="par0060" class="elsevierStylePara elsevierViewall">Severe infection&#44; if one or more of the following criteria are met&#58; systemic signs of infection&#44; leukocyte count &#8805;15&#44;000&#47;&#956;l or creatinine increase &#62;50&#37; the baseline level&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">o</span><p id="par0065" class="elsevierStylePara elsevierViewall">Severe-complicated infection&#44; if one or more of the following criteria are met&#58; hypotension or sepsis&#44; paralytic ileus&#44; toxic megacolon&#44; intestinal perforation&#44; ICU admission for CDI&#44; surgery for the same reason or attributable death&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">o</span><p id="par0070" class="elsevierStylePara elsevierViewall">Non-severe infection&#44; if it does not meet the criteria for severe or severe-complicated infection&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#9633;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Recurrence&#58; patient who meets the CDI criteria again within three to 60 days after a previous clinically resolved episode&#44; that is&#44; within eight weeks after having correctly completed treatment for the infection&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#9633;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Concomitant intestinal infection and infection in other locations&#46;</p></li></ul></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Microbiological diagnosis</span><p id="par0085" class="elsevierStylePara elsevierViewall">All loose stools received during the study period&#44; regardless of the clinician&#39;s request&#44; underwent an immunochromatographic test with simultaneous detection of glutamate dehydrogenase antigen and toxins A&#47;B &#40;C&#46; Diff Quik-Chek Complete&#174;&#44; Alere&#41;&#46; Discordant results were confirmed by loop-mediated isothermal amplification &#40;Illumigene&#174;&#44; Meridian Bioscience&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Bivariate analysis</span><p id="par0090" class="elsevierStylePara elsevierViewall">The response variable &#40;case&#47;control&#41; was related to each of the explanatory variables by preparing contingency tables for the qualitative variables&#46; To do this&#44; statistical significance was estimated &#40;<span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test or Fisher&#39;s exact test if the number of expected values is less than 5&#41; and a measure of the magnitude of the association in the form of the odds ratio and its corresponding confidence interval &#40;95&#37; CI&#41;&#46; For the quantitative variables&#44; the Student&#39;s <span class="elsevierStyleItalic">t</span>-test or the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test was used&#44; depending on the distribution of the variable&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Subsequently&#44; the cases were compared based on the type of infection acquisition &#40;nosocomial versus community&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Multivariate analysis</span><p id="par0100" class="elsevierStylePara elsevierViewall">All those explanatory variables that had a relationship with the response variable with a significance p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;20&#44; according to the criteria proposed by Maldonado and Greenland&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> formed part of the multivariate logistic regression models&#46; Conditional &#40;forward&#41; logistic regression was used due to the paired nature of the controls&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">To determine the unfavourable prognostic factors for CDI &#40;appearance of complications&#44; recurrences or attributable mortality&#41;&#44; the following variables were evaluated&#44; including symptoms and possible risk factors&#58; advanced age &#40;over 65 years&#41;&#44; gender&#44; type of acquisition&#44; previous hospital admission&#44; symptoms&#44; previous antibiotic exposure&#44; use of proton pump inhibitors&#44; immunosuppression&#44; enteral feeding&#44; hypoalbuminaemia and concomitant infections&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Statistical significance &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; was used as a criterion for permanence in the final model&#46; The calculations were made using the statistical program SPSS Statistics for Windows&#44; version 18&#46;0 &#40;SPSS Inc&#46;&#44; Chicago&#44; USA&#41;&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Ethical considerations</span><p id="par0115" class="elsevierStylePara elsevierViewall">This study was approved by the Ethics Committee of the Hospital General La Mancha Centro&#46; All the data collected throughout the conduct of the research project were processed in accordance with Spanish Organic Law 3&#47;2018&#44; of 5 December&#44; on the protection of personal data and guarantee of digital rights&#46; The database created for the conduct of this research was anonymised using codes and duly safeguarded by the principal investigator&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Results</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Descriptive analysis</span><p id="par0120" class="elsevierStylePara elsevierViewall">A total of 640 stool samples were analysed&#44; 61 of which were toxin A&#47;B positive&#44; representing 9&#46;5&#37; of CDI cases&#46; The incidence was 4&#46;51 cases per 10&#44;000 patient-days&#46; In all&#44; 61 cases &#40;72&#46;1&#37; nosocomial acquisition and 27&#46;9&#37; community&#41; and 64 controls were studied&#46; The monthly distribution of CDI cases was heterogeneous&#59; seasonality was observed &#40;greater in autumn and winter&#41; with an accumulation of 26 cases &#40;42&#46;6&#37;&#41; in the last quarter of 2015&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The median age of the cases was 80 years &#40;IQR 13 years&#59; range 28&#8211;95&#41;&#44; with a slight predominance of females &#40;57&#46;4&#37;&#41;&#46; The age histogram shows a heterogeneous distribution&#44; with a tendency to increase at advanced ages &#40;70&#8211;90 years&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Of the total&#44; 52&#37; of the cases came from the Internal Medicine Department&#44; 80&#37; had some underlying disease and 56&#37; some concomitant infection&#44; of which urinary tract infection and respiratory infections were the most common&#46; Meanwhile&#44; 52&#37; of the cases were associated with at least one gastrointestinal process&#58; enteral feeding and gastrointestinal cancer were the most common&#46; Additionally&#44; 26&#37; of the patients had a tumour&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The most common symptom was diarrhoea&#44; which affected all patients except one &#40;98&#46;4&#37;&#41;&#44; followed by fever &#40;42&#46;6&#37;&#41;&#44; abdominal pain &#40;24&#46;6&#37;&#41; and vomiting &#40;6&#46;5&#37;&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">A total of 129 antibiotics were administered&#46; Only three patients &#40;5&#37;&#41; did not receive any antibiotic before the development of the infection&#46; The most widely used family of antibiotics was beta-lactams &#40;56&#46;5&#37;&#41;&#44; followed by fluoroquinolones &#40;20&#46;1&#37;&#41;&#46; The most frequently administered antibiotics were&#58; amoxicillin-clavulanate &#40;20&#37;&#41;&#44; levofloxacin &#40;13&#37;&#41; and imipenem &#40;10&#37;&#41;&#46; Of the total&#44; 94&#46;4&#37; consumed antacids continuously&#44; of which omeprazole was the most used &#40;74&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">Meanwhile&#44; 34&#46;4&#37; of the cases developed a severe infection and&#44; of these&#44; 11&#46;5&#37; also had some type of complication&#59; five patients &#40;8&#46;5&#37;&#41; required admission to the ICU&#46; Overall mortality was 18&#37;&#44; while CDI-attributable mortality was 6&#46;6&#37;&#46; Twelve patients &#40;19&#46;7&#37;&#41; had a first recurrence&#44; and three of them suffered a second recurrence &#40;5&#37;&#41;&#46; Only one patient had a third recurrence &#40;1&#46;6&#37;&#41;&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Risk factors</span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Bivariate analysis</span><p id="par0150" class="elsevierStylePara elsevierViewall">Diarrhoea was the most common symptom in both groups&#44; although FAD was the only statistically significant symptom&#59; it was more common in cases than in controls &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The risk factors associated with CDI were nosocomial acquisition&#44; hospitalisation in the four weeks prior to infection&#44; previous use of antimicrobials and antacids&#44; hypoalbuminaemia and concomitant infections &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Multivariate analysis</span><p id="par0155" class="elsevierStylePara elsevierViewall">Using logistic regression analysis&#44; hospital admission in the four weeks prior to infection&#44; hypoalbuminaemia and prior administration of antibiotics were identified as independent risk factors for CDI &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The probability of developing a CDI when a patient presents one or none of these risk factors is 30&#37;&#44; rising to 70&#37; when presenting two factors and&#44; finally&#44; to 78&#37; when presenting three factors&#44; constituting an almost three times greater risk of acquiring the infection&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Prognostic factors for the clinical course of <span class="elsevierStyleItalic">Clostridioides difficile</span> infection</span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Bivariate analysis</span><p id="par0160" class="elsevierStylePara elsevierViewall">FAD&#44; hospital admission during the four weeks prior to infection&#44; hypoalbuminaemia and the presence of concomitant infections were found to be unfavourable prognostic factors &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Multivariate analysis</span><p id="par0165" class="elsevierStylePara elsevierViewall">FAD and hospital admission in the four weeks prior to infection were found to be independent prognostic factors for an unfavourable clinical course &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Comparison between hospital and community cases</span><p id="par0170" class="elsevierStylePara elsevierViewall">We found that 40&#37; of infections in patients under 65 years of age were community-acquired compared to 25&#37; in patients 65 years of age or older&#46; In all&#44; 82&#46;3&#37; of community cases were hospitalised&#46; In the nosocomial acquisition group&#44; we found a greater number of hospital admissions in the 4&#8722;12 weeks prior to the CDI&#44; a difference that was statistically significant &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#41;&#46; Enteral feeding was almost statistically significant&#46; However&#44; although we observed greater severity and&#44; in general&#44; a worse prognosis among hospital-acquired cases&#44; the differences were not statistically significant &#40;<a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Discussion</span><p id="par0175" class="elsevierStylePara elsevierViewall">In order to better understand the role of <span class="elsevierStyleItalic">C&#46; difficile</span> in our health area&#44; we conducted this research with 61 cases of CDI and 64 controls over a 14-month period&#46; Hospital admission four weeks prior to infection&#44; hypoalbuminaemia and prior antibiotic administration were risk factors for developing CDI&#46; However&#44; although other classic risk factors such as hospitalisation in the previous 4&#8722;12 weeks or the use of antacids and immunosuppressants were more common in cases than in controls&#44; they were not significantly associated with a higher risk of infection&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Spain has one of the highest antibiotic consumption rates of any European country&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> which&#44; together with an ageing population&#44; with numerous comorbidities and continuous hospitalisations&#44; creates the ideal breeding ground for acquiring CDI&#46; In our study&#44; we observed an incidence of 4&#46;51 cases per 10&#44;000 patient-days&#44; lower than that found in Spain &#40;6&#46;5 episodes per 10&#44;000 patient-days&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> We found a greater number of cases during the autumn&#47;winter months&#44; a time when respiratory infections and&#44; therefore&#44; antibiotic use increase&#44; often unnecessarily because they are viral infections&#44; such as the flu&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Community-acquired CDI has increased in the past decade&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> accounting for up to a third of new cases<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> and affecting population groups previously considered low risk&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> This increase in community cases could be explained&#44; in part&#44; by the fact that they have been underdiagnosed because they are mild and self-limiting cases&#46; Our results are consistent with these findings&#44; as 28&#37; of cases were community-acquired&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Our results showed that the CCDI group were younger patients&#44; with a shorter length of hospital stay and a lower risk of having a severe infection&#46; These findings are consistent with other published studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;11</span></a> Therefore&#44; these data emphasise the need to find other possible sources of infection that justify the increase in the number of cases in the community&#44; such as transmission of the disease through contact with animals and food&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">The use of antibiotics modifies the normal intestinal microbiota&#44; which provides a &#8220;niche&#8221; for the overgrowth of <span class="elsevierStyleItalic">C&#46; difficile</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> It must be taken into account that both prolonged exposure to antibiotics and exposure to multiple antibiotics increase the risk of CDI&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> In total&#44; 95&#37; of our patients had received antibiotics in the previous three months&#46; Since prior antibiotic exposure is the most important modifiable risk factor for the development of CDI&#44; we stress the importance of developing antibiotic optimisation programmes in both hospital and community settings&#46; Another modifiable CDI risk factor is hypoalbuminaemia&#44; which may be a key point in preventing infection&#46; Several studies show that hypoalbuminaemia is also a predictor variable of recurrent infection and higher mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> According to our data&#44; patients with hypoalbuminaemia have more than double the risk of acquiring a CDI&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">The incidence of colonisation by <span class="elsevierStyleItalic">C&#46; difficile</span> during hospitalisation varies between 2&#37; and 20&#37;&#44; reaching up to 50&#37; after being hospitalised for one month&#46; In our study&#44; hospitalisation in the previous four weeks resulted in an almost four times greater risk of infection&#46; In addition&#44; 35&#37; of the community-acquired cases had had a previous hospital admission&#46; These data confirm the importance of health centres as reservoirs of <span class="elsevierStyleItalic">C&#46; difficile</span> spores&#44; especially in emergency departments&#44; since the high volume of patients that are treated in each shift and the continuous turnover of patients limit the capacity for adequate disinfection between one patient and another&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">We have not been able to identify age as an independent risk factor for CDI since&#44; given the design of our study&#44; the controls were matched by age and gender with the cases&#46; The fact that the median age of the cases was 80 years indicates that age is indeed a potential risk factor for CDI&#46; Because several of the recognised risk factors for CDI are often found in the elderly&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> the line between a risk factor and a confounding factor may become blurred&#44; creating a certain degree of controversy in the results&#46; For example&#44; authors such as Khanafer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> do not associate age with infection&#44; while other authors&#44; like us&#44; do not find a statistically significant relationship with the administration of antacids<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46; However&#44; we observed a high continuous consumption in our patients&#44; so it would be advisable to reassess the need for their administration&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">The selection of appropriate controls is one of the points that can most influence the results of a case-control study design&#46; For this reason&#44; to avoid possible biases&#44; the controls closest in time and age to the cases were chosen&#46; The information collected in the medical records may not accurately reflect the data&#44; may be incomplete or even contain contradictory data&#46; However&#44; we believe that this information bias does not differentially affect cases and controls&#44; so we assume that it would not invalidate the associations found&#46; In addition&#44; we have tried to control for possible confounding factors in the estimates of associations&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">To provide a better understanding of the gaps in our knowledge regarding <span class="elsevierStyleItalic">C&#46; difficile</span> transmission&#44; we believe further studies are needed to determine whether animals are an important reservoir for CCDI<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> and whether <span class="elsevierStyleItalic">C&#46; difficile</span> can be transmitted after exposure to certain foods&#44; such as red meat&#44; poultry or fresh vegetables&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> In this way&#44; the lifestyle or profession of a patient could influence the risk of acquiring the infection&#44; either through their eating habits or through contact with domestic animals at home or at work in the case of veterinarians or farmers&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Conclusions</span><p id="par0220" class="elsevierStylePara elsevierViewall">The independent risk factors for acquiring a CDI in our health area are hospital admission in the previous four weeks&#44; previous administration of antibiotics&#44; and hypoalbuminaemia&#46; Identification of these factors leads to a suspicion of infection&#46; In addition&#44; we identified fever and previous hospitalisation as unfavourable prognostic factors&#46; By modifying or suspending antibiotic therapy whenever possible&#44; adjusting albumin levels and prescribing specific therapy early&#44; we can improve the prognosis of the infection&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Funding</span><p id="par0225" class="elsevierStylePara elsevierViewall">This study received no specific funding from public&#44; private or non-profit organisations&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Conflicts of interest</span><p id="par0230" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">To determine the risk and prognostic factors for <span class="elsevierStyleItalic">Clostridioides difficile</span> infection &#40;CDI&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Prospective&#44; case-control study with 61 cases and 64 controls&#44; aged &#8805; 2 years with diarrhoea&#44; carried out in &#8220;Castilla-La Mancha&#8221; Health Care Area &#8203;&#8203;for 14 months&#46; The diagnosis was made by immunochromatography technics &#40;glutamate dehydrogenase and toxin A&#47;B&#41;&#44; confirming discordant cases by isothermal amplification&#46; Demographic variables&#44; comorbidities&#44; type of acquisition&#44; previous administration of antibiotics&#44; antacids and immunosuppressants&#44; and evolution were collected&#46; The data were analysed using the chi-square test and the effect of risk and prognostic factors was quantified using an odds ratio with 95&#37; confidence intervals&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Hospital admission 4 weeks prior to infection&#44; hypoalbuminemia&#44; and previous administration of antibiotics were identified as independent risk factors for CDI&#46; Presenting these 3 factors constitutes nearly 3-fold increase in the risk of becoming infected&#46; A greater number of hospital admissions in the 4&#8722;12 weeks prior to CDI were found in the group of nosocomial acquisition&#46; Although there was a greater tendency to recurrence and an unfavourable prognosis among nosocomial cases&#44; these differences were not significant&#46; We found that fever and hospital admission in the 4 weeks prior to infection were unfavourable prognostic factors of CDI&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">The independent risk factors for CDI were&#58; hospital admission in the 4 weeks prior to infection&#44; hypoalbuminemia&#44; and previous administration of antibiotics&#46; Fever and hospitalisation in the previous 4 weeks were also identified as prognostic factors of unfavourable evolution&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Patients and methods"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Determinar los factores de riesgo y factores pron&#243;sticos de la infecci&#243;n por <span class="elsevierStyleItalic">Clostridioides difficile</span> &#40;ICD&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo de casos-controles &#40;61 casos y 64 controles&#41; &#8805;2 a&#241;os con diarrea&#44; atendidos en un &#193;rea Sanitaria manchega durante 14 meses&#46; El diagn&#243;stico se realiz&#243; mediante inmunocromatograf&#237;a &#40;glutamato deshidrogenasa y toxina A&#47;B&#41;&#44; realizando amplificaci&#243;n isot&#233;rmica en los casos discordantes&#46; Se recogieron variables demogr&#225;ficas&#44; comorbilidades&#44; tipo de adquisici&#243;n&#44; administraci&#243;n previa de antibi&#243;ticos&#44; anti&#225;cidos e inmunosupresores y evoluci&#243;n&#46; Los datos se analizaron mediante la prueba de chi-cuadrado y el efecto de los factores de riesgo y pron&#243;sticos se cuantific&#243; mediante odds ratio con intervalos de confianza del 95&#37;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">Como factores de riesgo independientes de ICD encontramos el ingreso hospitalario las 4 semanas previas a la infecci&#243;n&#44; la hipoalbuminemia y la administraci&#243;n previa de antibi&#243;ticos&#46; Presentar estos 3 factores supuso un riesgo casi 3 veces mayor de infectarse&#46; En el grupo de adquisici&#243;n nosocomial se encontr&#243; mayor n&#250;mero de ingresos hospitalarios las 4&#8722;12 semanas previas a la ICD&#44; y aunque hubo mayor tendencia a las recurrencias y pron&#243;stico desfavorable entre los casos intrahospitalarios&#44; estas diferencias no fueron significativas&#46; Identificamos como factores de pron&#243;stico desfavorable la fiebre y el ingreso hospitalario las 4 semanas previas a la infecci&#243;n&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">Los factores de riesgo independientes de ICD fueron&#58; ingreso hospitalario las 4 semanas previas a la infecci&#243;n&#44; hipoalbuminemia y administraci&#243;n previa de antibi&#243;ticos&#46; La fiebre y la hospitalizaci&#243;n las 4 semanas anteriores se identificaron adem&#225;s como factores pron&#243;sticos de evoluci&#243;n desfavorable&#46;</p></span>"
        "secciones" => array:4 [
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            "identificador" => "abst0025"
            "titulo" => "Objetivo"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Pacientes y m&#233;todos"
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
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        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Case-control study of <span class="elsevierStyleItalic">Clostridioides difficile</span> infection &#40;CDI&#41; in a rural health area&#46;</p>"
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          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">SD&#58; standard deviation&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Significant <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristics <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cases &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>61&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">73&#46;2 &#40;17&#46;4&#59; 11&#8722;98&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">75&#46;1 &#40;15&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;242&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Male&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">57 &#40;45&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">31 &#40;48&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26 &#40;42&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;514&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Female&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">68 &#40;54&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">33 &#40;51&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">35 &#40;57&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hospital-acquired&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">74 &#40;59&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">30 &#40;46&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">44 &#40;72&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Community-acquired&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">51 &#40;40&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">35 &#40;54&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">25 &#40;41&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Fever</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">32 &#40;25&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;15&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26 &#40;42&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Diarrhoea</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">119 &#40;95&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59 &#40;92&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60 &#40;98&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;208&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Abdominal pain</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">33 &#40;26&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Previous use of immunosuppressants</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">81 &#40;64&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42 &#40;65&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57 &#40;45&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;35&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;026&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t">4 &#40;3&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;3&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4 &#40;6&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;054&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;42&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;782&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68 &#40;54&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56 &#40;53&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;57&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Origin</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hospital-acquired&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65 &#40;52&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51 &#40;49&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;140&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Community-acquired&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Admission in previous 4&#8722;12 weeks</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">76 &#40;73&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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