Abstract Background C. difficile has been increasingly reported as a cause of gastrointestinal disease in children, ranging from mild self-limiting diarrhea to severe conditions such as pseudomembranous colitis and toxic megacolon. Only two pediatric research groups reported the presence of C. difficile infection in Brazilian children, but no previous research has examined C. difficile infection among children in northeastern Brazil. This prospective cross-sectional study investigated the molecular epidemiology and antimicrobial resistance of C. difficile strains isolated from children and adolescents with diarrhea referred to a tertiary pediatric hospital in Brazil while exploring the associated risk factors. Results Toxin positivity or C. difficile isolation was found in 30.4 % (17/56) samples. C. difficile was isolated from 35 % (6/17) samples. Four toxigenic strains were identified (tpi+, tcdA+, tcdB+, cdtB-, without tcdC deletions) belonging to PCR ribotypes and PFGE-pulsotypes: 046 (new pulsotype 1174), 106 (NAP11), 002 (new pulsotype 1274), 012 (new pulsotype NML-1235). Two of the six isolates belonging to ribotypes 143 and 133 were non-toxigenic. All toxigenic strains were sensitive to metronidazole and vancomycin. Regarding the clinical manifestation, diarrhea lasted an average of 11 days, ranging from 3 to 50 days and was often associated with mucus and/or blood. All six patients from whom the C. difficile was isolated had a chronic disease diagnosis, with these comorbidities as the main risk factors. Conclusion Our study enhances our understanding of the present epidemiological landscape of C. difficile-associated diarrhea (CDI) among children in northeastern Brazil, reveling a substantial CDI frequency of 30.4 %, with toxigenic strains detected in 76.4 % of cases, highlighting a higher prevalence compared to earlier Brazilian studies. In the globalized world, an understanding of disease-generating strains, the associated risk factors, clinical manifestation, and antimicrobial sensitivity has fundamental epidemiological importance and draws attention to preventive measures, allowing for more decisive action. C selflimiting self limiting megacolon crosssectional cross sectional factors 304 30 4 30. 17/56 1756 17 56 (17/56 samples 6/17 617 6 (6/17 tpi+, tpi (tpi+ tcdA tcdA+ tcdB tcdB+ cdtB, cdtB , cdtB- deletions PFGEpulsotypes PFGE pulsotypes PFGE-pulsotypes 04 new 1174, 1174 1174) 10 NAP11, NAP11 NAP (NAP11) 00 1274, 1274 1274) 01 NML1235. NML1235 NML 1235 . NML-1235) 14 13 nontoxigenic. nontoxigenic non toxigenic. non-toxigenic vancomycin manifestation 1 5 andor blood diagnosis difficileassociated (CDI 764 76 76. cases studies world diseasegenerating generating measures action 17/5 175 (17/5 6/1 61 (6/1 tpi+ (tpi 0 117 NAP1 (NAP11 127 NML123 123 NML-1235 7 17/ (17/ 6/ (6/ (NAP1 12 NML12 NML-123 (17 (6 (NAP NML1 NML-12 (1 ( NML-1 NML-

Resumen Objetivo: Describir las características de los pacientes adultos mayores con diagnóstico de infecciones por Clostridium difficile en un hospital geriátrico en Costa Rica con el propósito de contribuir a mejorar su manejo y llevar a una reducción de la morbimortalidad y costos asociados a su atención. Métodos: Se realizó un estudio observacional retrospectivo con información demográfica y clínica de 141 pacientes admitidos en el Hospital Nacional de Geriatría y Gerontología Dr. Raúl Blanco Cervantes de Costa Rica del 2015 al 2018, quienes presentaron una prueba inmunocromatográfica de detección de antígeno y/o toxinas de C. difficile positiva en heces diarreicas. Las variables continuas se compararon mediante una prueba de ANOVA, mientras que las categóricas, por una prueba exacta de Fisher. Los factores de riesgo para cada uno de los grupos se evaluaron por análisis univariante. Los valores de p < 0,05 se consideraron estadísticamente significativos con un 95% de confianza. Resultados: Se estudiaron 141 pacientes con diarrea asociada a C. difficile. Los pacientes tenían una edad promedio de 83 años y 57% eran mujeres. Un 35% de los casos eran de origen comunitario y 27% fueron severos. El consumo de antimicrobianos fue dado principalmente por cefalosporinas y fluoroquinolonas. El tratamiento más utilizado fue el metronidazol (81%) y la mortalidad relacionada con la infección por C. difficile a los 30 días fue de un 35%. Conclusiones: Este es el primer reporte epidemiológico de infección por C. difficile que describe a un grupo de pacientes geriátricos hospitalizados y sus factores de riesgo asociados, que pone en manifiesto un porcentaje importante de casos comunitarios y graves, lo que llama a establecer guías locales y grupos específicos para el tratamiento y prevención de dicha infección.

Abstract Aim: To describe the characteristics of elder patients diagnosed with Clostridioides (Clostridium) difficile infection in a geriatric hospital in Costa Rica. Methods: A retrospective observational study was done with demographic and clinical information from 141 patients admitted in the National Geriatric and Gerontology Hospital of Costa Rica from 2015 to 2018, who presented a positive immunochromatographic test for the detection of C. difficile antigen and/or toxins in diarrheic feces. Continuous variables were compared through one-way ANOVA test, while categorical variables were compared using Fisher's exact test. The risk factors for each of the groups were evaluated by univariate analysis. P values < 0.05 were considered statistically significant with 95% confidence. Results: We studied 141 patients with diarrhea associated with C. difficile, the average age of the patients was 83 years and 75% were women. 35% of the cases were community acquired and 27% were severe cases. Antimicrobial consumption was given mainly by cephalosporins and fluoroquinolones. Metronidazol was the most used treatment (81%) and the C. difficile associated mortality 30 days post infection was 35%. Conclusion: This is the first epidemiological report of C. difficile infection in elderly hospitalized population. Also, it evidences an important percentage of community acquired and severe cases, calling for the establishment of local treatment and prevention guidelines for this infection.

Resumen: Esta revisión tiene como principal objetivo sintetizar, reunir y resumir algunos aspectos relacionados con Clostridioides difficile y su papel como microbiota y patógeno en porcinos. C. difficile es una bacteria anaerobia, esporulada y uno de los principales agentes etiológicos de la diarrea asociada al uso de antibióticos. Los principales factores de virulencia son dos toxinas (A y B) que causan daños en el epitelio del colon cuando se presenta una disbiosis, generalmente producida por el uso de antibióticos. Se ha determinado que esta bacteria tiene una alta prevalencia en porcinos, principalmente en los primeros meses de vida del animal y además muchos de estos animales colonizados con cepas no toxigénicas de C. difficile. Sin embargo, también existen reportes de casos de gastroenteritis producidas por esta bacteria y posiblemente relacionada con el uso y abuso de los antibióticos, aunque las causas de estas infecciones en porcinos aún no están completamente claras y requiere de una mayor investigación. Uno de los genotipos de C. difficile que se aíslan en los cerdos es el RT028 y el cual también ha sido reportado produciendo brotes epidémicos en hospitales humanos, por lo que se ha postulado una posible zoonosis, aunque esta hipótesis no ha sido totalmente demostrada. Adicionalmente, la resistencia a los antimicrobianos en aislamientos de C. difficile en cerdos es considerable y se han reportado fenotipos multirresistentes, por lo que esta bacteria podría estar funcionando como un reservorio ecológico de genes de resistencia a los antimicrobianos. Finalmente, se considera la necesidad de establecer medidas para el uso racional de los antibióticos en las granjas porcinas y un sistema de vigilancia sobre los genotipos circulantes y la resistencia de C. difficile en cerdos.

Abstract: The aim of this review is to synthesize, gather and summarize some aspects related to Clostridioides difficile and its role as microbiota and pathogen in pigs. C. difficile is an anaerobic, sporulated bacterium and one of the main etiological agents of diarrhea associated with the use of antibiotics. The main virulence factors are two toxins (A and B) that cause damage to the colon epithelium when a dysbiosis occurs, usually caused by antibiotics. It has been determined that this bacterium has a high prevalence in pigs, mainly in the first months of the animal's life and also many of these animals colonized with non-toxigenic strains of C. difficile. However, there are reports of gastroenteritis caused by this bacterium and possibly related to the use and abuse of antibiotics, although the causes of these infections in swine are not yet completely clear and require further investigation. RT028 is one of the most frequently isolated C. difficile genotypes in pigs, which has also been reported causing epidemic outbreaks in human hospitals; therefore, a possible zoonosis has been postulated, although this hypothesis has not been fully demonstrated. Additionally, high antimicrobial resistance of C. difficile isolates from pigs and multi-resistant phenotypes has been reported. Thus this bacterium could be functioning as an ecological reservoir of antimicrobial resistance genes. Finally, it is necessary to establish measures for the rational use of antibiotics in pig farms and a surveillance system on circulating genotypes and resistance of C. difficile in pigs.