Study on the features of Clostridioides difficile infection among diarrhea patients in Kunming from 2018 to 2020 / 中华流行病学杂志

Objective: We analyze the characteristics of Clostridioides difficile (C. difficile) infection among diarrhea patients in Kunming from 2018 to 2020 and provide evidence for follow-up surveillance and prevention. Methods: A total of 388 fecal samples of diarrhea patients from four sentinel hospitals in Yunnan Province from 2018 to 2020 were collected. Real-time quantitative PCR was used to detect the fecal toxin genes of C. difficile. The positive fecal samples isolated the bacteria, and isolates were identified by mass spectrometry. The genomic DNA of the strains was extracted for multi-locus sequence typing (MLST). The fecal toxin, strain isolation, and clinical patient characteristics, including co-infection with other pathogens, were analyzed. Results: Among the 388 fecal samples, 47 samples with positive reference genes of C. difficile were positive, with a total positive rate of 12.11%. There were 4 (8.51%) non-toxigenic and 43 (91.49%) toxigenic ones. A total of 18 strains C. difficile were isolated from 47 positive specimens, and the isolation rate of positive specimens was 38.30%. Among them, 14 strains were positive for tcdA, tcdB, tcdC, tcdR, and tcdE. All 18 strains of C. difficile were negative for binary toxins. The MLST results showed 10 sequence types (ST), including 5 strains of ST37, accounting for 27.78%; 2 strains of ST129, ST3, ST54, and ST2, respectively; and 1 strain of ST35, ST532, ST48, ST27, and ST39, respectively. Fecal toxin gene positive (tcdB+) results were statistically associated with the patient's age group and with or without fever before the visit; positive isolates were only statistically associated with the patient's age group. In addition, some C. difficile patients have co-infection with other diarrhea-related viruses. Conclusions: The infection of C. difficile in diarrhea patients in Kunming is mostly toxigenic strains, and the high diversity of strains was identified using the MLST method. Therefore, the surveillance and prevention of C. difficile should be strengthened.

¿La detección de toxinas de Clostridioides difficile es necesaria cuando se detecta la enzima glutamato deshidrogenasa? / Is Clostridioides difficile toxins detection necessary when the glutamate dehydrogenase enzyme is detected?

Resumen Introducción: Clostridioides difficile causa diarrea y colitis pseudomembranosa. Su diagnóstico se realiza con la detección de glutamato-deshidrogenasa (GDH) o las toxinas A y B y se confirma con pruebas de amplificación de ácidos nucleicos. Objetivo: Definir si la determinación de GDH es redundante a la de las toxinas. Métodos: Estudio observacional retrospectivo de muestras fecales de pacientes con sospecha de infección por Clostridioides difficile. Las toxinas y GDH se determinaron mediante inmunocromatografía. Se realizó una simulación bayesiana con los cocientes de probabilidad; se consideró significativo un valor de p < 0.05. Resultados: Se analizaron 329 resultados de GDH y toxinas A y B. Se encontró una prevalencia de infección de Clostridioides difficile de 18.2 %. La sensibilidad y especificidad de la prueba de GDH fue de 0.90 y 0.89, respectivamente. El cociente de probabilidad positivo fue de 8.9 y el negativo, de 0.11. Conclusiones: Un resultado negativo de GDH disminuye considerablemente la probabilidad de infección, pero no la descarta. La detección de toxinas de Clostridioides difficile puede ser necesaria en instituciones donde la amplificación de ácidos nucleicos no es económica o accesible.

Abstract Introduction: Clostridioides difficile causes diarrhea and pseudomembranous colitis. Its diagnosis is made with glutamate dehydrogenase (GDH) or toxins A and B detection and is confirmed with nucleic acid amplification tests. Objective: To define if GDH determination is redundant to that of toxins. Methods: Retrospective, observational study in diarrheal stools of patients with suspected Clostridioides difficile infection. Toxins and GDH were determined by immunochromatography. Bayesian simulation was performed with likelihood ratios; a p-value < 0.05 was regarded as significant. Results: 329 GDH and toxin A and B results were analyzed. Clostridioides difficile infection prevalence was 18.2 %. Sensitivity and specificity of the GDH test were 0.90 and 0.89, respectively. Positive likelihood ratio was 8.9, and negative was 0.11. Conclusions: A negative GDH result considerably reduces the probability of infection but does not rule it out. Clostridioides difficile toxins detection may be necessary in institutions where nucleic acid amplification is not affordable or accessible.

Assessing risk factors, mortality, and healthcare utilization associated with Clostridioides difficile infection in four Latin American countries

ABSTRACT Background: Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated infections in Western countries. Risk factors, mortality, and healthcare utilization for CDI in Latin America are poorly understood. This study assessed risk factors and burden associated with nosocomial CDI in four Latin American countries. Methods: This retrospective, case-control study used databases and medical records from 8 hospitals in Argentina, Brazil, Chile, and Mexico to identify nosocomial CDI cases from 2014 − 2017. Cases were patients aged ≥18 years with diarrhea and a positive CDI test ≥72 h after hospital admission. Two controls (without diarrhea; length of hospital stay [LOS] ≥3 days; admitted ±14 days from case patient; shared same ward) were matched to each case. CDI-associated risk factors were assessed by univariate and multivariable analyses. CDI burden (LOS, in-hospital mortality) was compared between cases and controls. Results: The study included 481 cases and 962 controls. Mean age and sex were similar between cases and controls, but mean Charlson comorbidity index (4.3 vs 3.6; p< 0.001) and recent hospital admission (35.3% vs 18.8%; p< 0.001) were higher among cases. By multivariable analyses, CDI risk was associated with prior hospital admission within 3 months (odds ratio [OR], 2.08; 95% CI: 1.45, 2.97), recent antibiotic use (ie, carbapenem; OR, 2.85; 95% CI: 1.75, 4.64), acid suppressive therapy use (OR, 1.71; 95% CI: 1.14, 2.58), and medical conditions (ie, renal disease; OR, 1.48; 95% CI: 1.19, 1.85). In-hospital mortality rate (18.7% vs 6.9%; p< 0.001) and mean overall LOS (33.5 vs 18.8 days; p< 0.001) were higher and longer, respectively, in cases versus controls. Conclusion: Antibiotic exposure, preexisting medical conditions, and recent hospital admission were major risk factors for CDI in Argentina, Brazil, Chile, and Mexico. CDI was associated with increased in-hospital risk of death and longer LOS. These findings are consistent with published literature in Western countries.

Trasplante de microbiota fecal / Fecal microbiota's transplant

Introducción: El trasplante de microbiota fecal se basa en la infusión de material fecal de un sujeto sano a otro enfermo por afección específica relacionada con disbiosis de la microbiota intestinal. Entre las indicaciones usadas con resultados promisorios en los últimos 20 años sobresalen infección por Clostridium difficile. Objetivo: Analizar los conocimientos más avanzados y ventajas del trasplante de microbiota fecal en distintas afecciones en el humano, en especial en la infancia. Métodos: Se revisaron las publicaciones sobre esta afección en español e inglés en bases de datos de PubMed, Google Scholar, SciELO y Latindex desde el 2015 hasta el 20 de enero de 2019 Resultados: Se determinan los antecedentes históricos, criterios para indicación del trasplante de microbiota fecal, procedimiento de selección del donante, preparación y conservación de la material fecal, vías de administración, riesgos y efectos adversos, y resultados alcanzados en los últimos años a nivel mundial. Se ha descrito 90 por ciento de resolución de los síntomas en la infección recurrente por Clostridium difficile. Consideraciones finales: El trasplante de microbiota fecal es un tratamiento eficaz y seguro, de fácil realización y buena tolerancia, con repercusión económica y científica, cuya principal indicación aprobada por organizaciones internacionales de la comunidad médica es la infección recurrente o recaída de Clostriium difficile en adultos y niños. Otras indicaciones ensayadas son enfermedades inflamatorias crónicas intestinales, en especial la colitis ulcerosa; síndrome de intestino irritable, enfermedades metabólicas como la obesidad y diabetes mellitus tipo 2 y neuropsiquiátricas que se asocian con desequilibrio de la microbiota intestinal (AU)

Introduction: Fecal microbiota´s transplant (TMF, by its acronym in Spanish) is based on the infusion of fecal material from a healthy subject to another patient due to a specific condition related to intestinal microbiota dysbiosis. Among the indications used with promising results in the last 20 years are the ones used for the infection by Clostridium difficile. Objective: To analyze the most advanced knowledge and advantages of TMF in different conditions in humans, especially in childhood Method: Publications on this condition in Spanish and English in PubMed, Google Scholar, SciELO and Latindex databases from 2015 to January 30, 2019 were reviewed. Results: Historical background, criteria for indication of TMF, donor's selection procedure, preparation and preservation of fecal material, administration routes, risks and adverse effects, and results achieved in recent years worldwide are determined. 90 percent resolution of symptoms in recurrent infection by Clostridium difficile is described. Final considerations: The TMF is an effective and safe treatment, easy to perform and of good tolerance, with economic and scientific impact, whose main indication approved by international organizations of the medical community is the recurrent infection or relapse of Clostriium difficile in adults and children. Other indications tested are chronic intestinal inflammatory diseases, especially ulcerative colitis; irritable bowel syndrome, metabolic diseases as obesity and diabetes mellitus type 2, and neuropsychiatric ones that are associated with imbalance of the intestinal microbiota(AU)

Factores de riesgo para mortalidad en pacientes con infección por Clostridium difficile / Risk factors for mortality in patients with Clostridium difficile infection

Resumen Introducción: La infección por Clostridium difficile (ICD) es causa de diarrea hospitalaria potencialmente letal. Objetivo: Identificar los factores de riesgo para mortalidad en pacientes hospitalizados con ICD. Método: Estudio transversal y retrospectivo. Se analizaron factores de riesgo: edad, comorbilidades, estado nutricional, antecedente y uso de antibióticos, de inhibidores de bomba de protones, esteroides, inmunosupresores, quimioterapia y desarrollo de lesión renal aguda (LRA). Resultados: Fueron evaluados 68 casos (incidencia de 25.7/10 000 egresos hospitalarios). La edad fue de 51.4 ± 19.37 años y la mortalidad de 22.2 %. La desnutrición moderada a severa mostró RM = 20.15, IC 95 % = 1.13-35, p = 0.004; el uso de más de dos antibióticos, RM = 1.61, IC 95 % = 0.39-6.65, p = 0.01; la LRA determinada por elevación de los niveles de creatinina, RM = 1.34, IC 95 % = 0.09-2.21, p = 0.02; la hipotensión con uso de vasopresores, RM = 1.28, IC 95 % = 0.30-1.23, p = 0.001; y el desarrollo de falla orgánica múltiple (FOM), RM = 1.13, IC 95 % = 0.31-4.92, p = 0.002. Conclusiones: La desnutrición moderada a severa, el uso de más de dos antibióticos, la LRA, la hipotensión con uso de vasopresores y la FOM se asocian con incremento en la mortalidad en pacientes con ICD.

Abstract Introduction: Clostridium difficile infection (CDI) causes potentially lethal diarrhea. Objective: To identify the risk factors for mortality in hospitalized patients with CDI. Method: Cross-sectional, retrospective study. The analyzed risk factors were age, comorbidities, nutritional status, past and current use of antibiotics, proton pump inhibitors, steroids, immunosuppressive therapy and chemotherapy, as well as development of acute kidney injury (AKI). Results: Sixty-eight cases were assessed. Mean age was 51.4 ± 19.37 years. Mortality was 22.2 %. Moderate to severe undernutrition (Odds ratio [OR] = 20.15; 95% confidence interval [CI] = 1.13-35; p = 0.004), use of more than 2 antibiotics (OR = 1.61; 95% CI = 0.39-6.65; p = 0.01), AKI as determined by creatinine levels (OR = 1.34; 95% CI = 0.09-2.21; p = 0.02), hypotension with vasopressor use (OR = 1.28; 95% CI = 0.30-1.23; p = 0.001) and multiple organ failure (OR = 1.13; 95% CI = 0.31-4.92; p = 0.002) were associated with mortality. Conclusions: CDI represents an important problem in hospitalized patients and confers them an additional morbidity and mortality risk.

Clostridial diseases diagnosed in cattle from the South of Rio Grande do Sul, Brazil. A forty-year survey (1978-2018) and a brief review of the literature / Clostridioses diagnosticadas em bovinos no sul do Rio Grande do Sul. Uma pesquisa de quarenta anos (1978-2018) e breve revisão da literatura

Clostridial diseases are important causes of livestock losses in the southern Rio Grande do Sul. Since 1978 annual surveys conducted at the "Laboratório Regional de Diagnóstico" of the "Universidade Federal de Pelotas" (LRD-UFPel) have shown that clostridial diseases represent 10.40% of the bacterial diseases diagnosed in cattle and 1.65% of all diseases diagnosis in cattle over a 40-year period. The purpose of this study is to review the clinical, epidemiological and pathological aspects of the clostridial diseases diagnosed in cattle from January 1978 to December 2018 at the LRD-UFPel in the hopes that it will constitute a useful guide for field veterinary practitioners and interested farmers. We assessed and review the necropsy protocols of 6,736 cattle; these necropsies were performed either by LRD-UFPel faculty or by field veterinary practitioners; 111 outbreaks (1.65%) were diagnosed as clostridial disease, distributed as follows: 35 outbreaks of tetanus, 34 of blackleg, 23 of bacillary hemoglobinuria, 11 of malignant edema (gas gangrene), and eight of botulism. Approximately 904, from a total of 42,480 cattle at risk, died in these outbreaks.(AU)

Clostridioses são doenças produzidas por alguma das espécies do gênero Clostridium e são importantes causas de perdas pecuárias no sul do Rio Grande do Sul. Pesquisas anuais realizadas no Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas (LRD-UFPel) desde 1978 demonstraram que as clostridioses representaram 11,1% das doenças bacterianas diagnosticadas em bovinos e 1,65% de todos os diagnósticos de doenças em bovinos ao longo de 40 anos. O objetivo deste estudo é revisar os aspectos clínicos, epidemiológicos e patológicos das clostridioses diagnosticadas de janeiro de 1978 a dezembro de 2018, pelo LRD/UFPel com a intenção de que esse trabalho possa servir de guia útil para os veterinários de campo e fazendeiros interessados. Foram avaliados e revisados os protocolos de necropsia de 6.736 bovinos; essas necropsias foram realizadas pelo pessoal do LRD/UFPel ou por veterinários de campo. Cento e quatro (1,16%) casos foram diagnosticados como clostridioses, distribuídos da seguinte forma: 35 surtos de tétano, 34 de carbúnculo sintomático, 23 de hemoglobinúria bacilar, 11 de edema maligno (gangrena gasosa) e oito de botulismo. Aproximadamente 904, de um total de 42.480 bovinos sob-risco, morreram nesses surtos.(AU)

Infección por Clostridium difficile: descripción de las cepas NAP1/027 y de otros serotipos en un centro de alta complejidad de Cali, Colombia, 2012-2015 / Clostridium difficile infection: Description of NAP1/027 and non NAP1/027 strains in a high complexity center in Cali, Colombia, 2012-2015

Resumen Introducción. Clostridium difficile ocasiona infecciones hospitalarias que resultan en altas tasas de morbilidad y mortalidad. La cepa NAP1/027 se ha asociado con una mayor producción de toxinas y con una mayor gravedad, lo que aumenta la carga de la enfermedad. Objetivo. Describir la epidemiología de las infecciones asociadas con C. difficile y las características de la cepa NAP1/027. Materiales y métodos. Se hizo un estudio observacional basado en la revisión de las historias clínicas de los pacientes con muestras de heces positivas para C. difficile identificadas mediante la prueba Xpert™ entre el 2012 y el 2015 en un hospital de alta complejidad. La gravedad de la enfermedad se evaluó con el índice ATLAS. Resultados. Se incluyeron 42 casos de pacientes infectados, 9 de los cuales fueron positivos para la cepa NAP1/027. El uso de antibióticos antes de la infección durante más de siete días fue más frecuente en los casos de pacientes con muestras negativas para NAP1/027. En la mitad de los pacientes, la duración de la diarrea fue mayor de cinco días y no hubo diferencias según el tipo de cepa (p>0,05). Los casos de pacientes positivos para la cepa NAP1/027 se caracterizaron por presentar deposiciones fétidas y sanguinolentas. La gravedad de la infección fue similar entre los grupos. Conclusión. Se comprobó la circulación de la cepa NAP1/027, pero su presencia no supuso diferencias clínicas significativas con respecto a otras cepas, lo cual podría deberse al limitado número de pacientes en este estudio. Sin embargo, su presencia debe alertar a los médicos y a las instituciones de salud, dada su frecuente asociación con la gravedad de la infección y la mortalidad.

Abstract Introduction: Clostridium difficile causes nosocomial infections leading to high morbidity and mortality. The NAP1/027 strain is associated with a higher toxin production and disease severity, which increases the load of the disease. Objective: To describe the epidemiology of the infections associated with C. difficile and the characteristics related to the NAP1/027 strain. Materials and methods: This was an observational study based on the revision of clinical registries of patients with fecal samples that were positive for C. difficile identified by the Xpert test™ between 2012 and 2015 in a high complexity institution. The severity of the disease was evaluated by means of the ATLAS score. Results: We included 42 infected cases, 9 of which were positive for the NAP1/027strain. The use of antibiotics previous to the infection for more than seven days was more frequent in patients with negative results for NAP1/027. The duration of diarrhea in half of the patients was longer than five days and there were no differences according to the type of strain (p>0.05). Positive cases for the NAP1/027 strain were characterized by presenting fetid and bloody stools. The severity of the infection was similar between the groups. Conclusions: In Colombia, the NAP1/027 strain circulates without significant clinical differences, which could be due to the limited number of patients. Nevertheless, the existence of NAP1/027 should alert physicians and health institutions because of its high association with severity and mortality.

Clostridium difficile contamination in retail meat products in Brazil

ABSTRACT Introduction Clostridium difficile is an important cause of diarrhoea, particularly in patients receiving antibiotic therapy. Recent studies have shown that a substantial proportion of C. difficile infections are acquired in the community, as a zoonotic disease. Brazil is a large exporter of meat and so far no study has evaluated meat contamination with C. difficile spores. Methods Here we analysed 80 retail meat products purchased from local supermarkets in a Brazilian metropolis (Porto Alegre, Southern Brazil). Samples from these products were grown in anaerobic conditions, and tested with a real time polymerase chain reaction test. Results Contamination with C. difficile spores was not found in the study. Bacteria isolated from meat included Streptococcus gallolyticus, Lactobacillus plantarum, Enterococcus gallinarum and Pediococcus acidilactici. Discussion Close vigilance is required in order to guarantee the quality of Brazilian retail meat in the long term.

Características de la infección por Clostridium difficile en una institución de alta complejidad y reporte de la circulación en Colombia de la cepa hipervirulenta NAP1/027 / Characteristics of Clostridium difficile infection in a high complexity hospital and report of the circulation of the NAP1/027 hypervirulent strain in Colombia

Resumen Introducción. Clostridium difficile es el principal responsable de la diarrea asociada al uso de antibióticos. En Colombia y en Latinoamérica, el conocimiento sobre el comportamiento epidemiológico de la infección por C. difficile todavía es limitado. Objetivo. Describir las características de una serie de pacientes con infección por C.difficile . Materiales y métodos. Se hizo un estudio descriptivo de una serie de casos de pacientes con infección por C. difficile atendidos en la Fundación Clínica Shaio, entre enero de 2012 y noviembre de 2015. Resultados. Se estudiaron 36 pacientes con una edad promedio de 65 años. Se determinaron los siguientes factores relacionados con la infección por C. difficile: uso previo de antimicrobianos (94,4 %), hospitalización en los últimos tres meses (66,7 %) y uso de inhibidores de la bomba de protones (50 %). Las comorbilidades más comunes fueron la enfermedad renal crónica (41,7 %) y la diabetes mellitus (30,6 %). Los síntomas más frecuentes fueron más de tres deposiciones diarreicas (97,1 %) y dolor abdominal (42,9 %). En cuanto a la gravedad de los casos, 44,4 % se clasificó como leve a moderado, 38,9 % como grave, y 11,1 % como complicado o grave. El método de diagnóstico más utilizado (63,8% de los pacientes) fue la identificación de la toxina mediante reacción en cadena de la polimerasa (PCR). La mortalidad global durante la hospitalización fue de 8 %. Se identificaron cuatro cepas del serotipo NAP1/027 y nueve muestras fueron positivas para la toxina binaria. Conclusión. La infección por C. difficile debe sospecharse en pacientes con deposiciones diarreicas y factores asociados tradicionalmente a esta enfermedad. Se reportó la circulación de cepas hipervirulentas del serotipo NAP1/027 en Colombia, lo cual debe enfrentarse con la vigilancia epidemiológica y el diagnóstico temprano.

Abstract Introduction: Clostridium difficile is the main pathogen related to healthcare-associated diarrhea and it is the cause of 20 to 30% of diarrhea cases caused by antibiotics. In Colombia and Latin America, the knowledge about the epidemiological behavior of this infection is limited. Objective: To describe the characteristics of a series of patients with C. difficile infection. Materials and methods: We performed a descriptive case series study of patients with C. difficile infection hospitalized in the Fundación Clínica Shaio from January, 2012, to November, 2015. Results: We analyzed 36 patients. The average age was 65 years. The risk factors associated with the infection were: previous use of antibiotics (94.4%), prior hospitalization in the last three months (66.7%) and use of proton pump inhibitors (50%). The most common comorbidities were chronic kidney disease (41.7%) and diabetes mellitus (30.6%). The most frequent symptoms were more than three loose stools per day (97.1%) and abdominal pain (42.9%). According to the severity of the disease, 44.4% of cases were classified as mild to moderate, 38.9% as severe, and 11.1% as complicated or severe. The detection of the toxin by PCR (GeneXpert) was the most common diagnostic procedure (63.8%). Global mortality during hospitalization was 8%. We identified four strains with serotype NAP1/027 and nine samples positive for binary toxin. Conclusion: Clostridium difficile infection should be suspected in patients with diarrhea and traditional risk factors associated with this disease. We report the circulation of the hypervirulent strain serotype NAP1/027 in Colombia, which should be countered with epidemiological surveillance and a prompt diagnosis.

Increasing rates of Clostridium difficile infection in Mexican hospitals

Abstract Introduction The epidemiology of Clostridium difficile infection (CDI) has changed in the last two decades. There is a lack of information regarding incidence and severity of CDI, especially in the developing world. Methods This was a retrospective and observational study from four hospitals of three Mexican cities. Patients were diagnosed with CDI when presented with loose stools and had at least one of the following tests positive: toxins assay, real-time PCR, or an endoscopic image compatible with pseudomembranous colitis. CDI was classified according to international guidelines. Demographic and clinical data as well as information regarding total hospital admissions, total length-of-hospital stay, and other variables related to hospitalization were gathered from the epidemiology and administration departments of each hospital. Results A total of 2050 hospital beds were analyzed with 288,171 patients hospitalized accumulating 1,576,446 days of hospitalization during the study period. The average rate of CDI per 1000 hospital-days was lower than the rates reported in the US and Europe, although in 2015 CDI rates were almost persistently above the mean rate for the study period. More than half of PCR positive patients were ribotype 027. Conclusion Hospital rates of CDI are increasing in Mexican hospitals with a predominance of infections caused by ribotype 027.

Informe especial: Tétanos otras edades (No neonatal) / Special report: Tetanus other ages (Nonneonatal)

Entre las Semanas Epidemiológicas (SE) 51 del año 2016 y 5 del 2017 (período comprendido entre el 18/12/2016 y el 04/02/2017), la Gerencia Operativa de Epidemiología recibió la notificación de 3 casos de tétanos otras edades a través de alertas del módulo C2 del Sistema Nacional de Vigilancia de la Salud (SNVS). Se trató de 3 pacientes asistidos en el Departamento de Atención Intensiva del Paciente Infeccioso Crítico (D.A.I.P.I.C.), del Hospital de Infecciosas Francisco Muñiz, de la Ciudad de Buenos Aires. Dos casos correspondieron a residentes de Provincia de Buenos Aires y el restante a un residente de la Ciudad. Este informe resume estos tres casos, los cuales destacan la necesidad que los médicos y quienes están encargados de los cuidados de salud, constaten en oportunidad de toda consulta, la cobertura de vacunación antitetánica e indiquen la vacuna a pacientes no vacunados, incompletamente vacunados o con vacunación desconocida.(AU)

Perfil clínico y demográfico y factores de riesgo frente a la infección por Clostridium difficile / Clinical and demographic profile and risk factors for Clostridium difficile infection

Resumen Introducción: La enfermedad asociada a Clostridium difficile es la principal causa de diarrea infecciosa adquirida en el hospital; su creciente incidencia, las menores tasas de respuesta al tratamiento inicial y la mayor tasa de recaídas han incrementado la carga de la enfermedad. Objetivo: Determinar las características clínicas de los pacientes hospitalizados con enfermedad asociada a C. difficile. Materiales y métodos: Se hizo un estudio de casos anidado en una cohorte. Se revisaron las historias clínicas de pacientes con diarrea iniciada durante su hospitalización a quienes se les había practicado la prueba de detección de la toxina A-B de C. difficile, entre febrero de 2010 y febrero de 2012. Se definió como caso al paciente hospitalizado con diarrea y prueba de Enzyme Linked Fluorescent Assay (ELFA) positiva para la toxina y, como control, a aquel con resultado negativo para la toxina. Se recolectaron los datos demográficos y clínicos, así como la información sobre los factores asociados, la estancia hospitalaria, el tratamiento y las complicaciones. Resultados: Durante el periodo de seguimiento se recolectaron datos de 123 pacientes, de los cuales 30 fueron positivos para la toxina. La edad media en la población de estudio fue de 49 años y el 60 % correspondía a hombres. Los síntomas predominantes fueron el dolor abdominal (35 %) y la fiebre (34 %). Las principales complicaciones fueron la alteración electrolítica y la sepsis grave asociada con disfunción renal. La mortalidad total fue de 13 % y los factores independientes asociados con la aparición de la infección fueron el uso de inhibidores de la bomba de protones y la cirugía gastrointestinal previa. Conclusiones: El uso de inhibidores de la bomba de protonesy la cirugía gastrointestinal previa fueron factores asociados con la infección por C. difficile.

Abstract Introduction: Clostridium difficile infection is the leading cause of nosocomial infectious diarrhea. The increasing incidence added to a lower rate of response to the initial treatment and higher rates of relapse has generated a higher burden of the disease. Objective: To determine the clinical characteristics of hospitalized patients with C. difficile infection. Materials and methods: We made a nested case-cohort study. We reviewed medical records of the patients with nosocomial diarrhea for whom an assay for toxin A-B of C. difficile had been requested from February, 2010, to February, 2012. We defined case as a patient with diarrhea and a positive assay for the toxin, and control as those patients with a negative assay for the toxin. We collected data on demographic and clinical characteristics, risk factors, hospital length of stay, treatment, and complications. Results: We collected data from 123 patients during the follow-up period, 30 of whom were positive for the toxin. Mean age in the study population was 49 years and 60% were men. The main symptoms were abdominal pain (35%) and fever (34%). The principal complications were electrolytic alteration and severe sepsis with secondary acute kidney injury. Mortality was 13% and independent factors associated to the appearance of the infection were the use of proton pump inhibitors and previous gastrointestinal tract surgery. Conclusions: The use of proton pump inhibitors and previous gastrointestinal tract surgery were factors associated to C. difficile infection.

Prevalencia y factores relacionados con la infección por Clostridium difficile en un centro hospitalario de alta complejidad en Cali (Colombia) / Prevalence and factors related to Clostridium difficile infection in a high complexity hospital in Cali, Colombia

Objetivos: Estimar la prevalencia y los factores relacionados con la infección por Clostridium difficile en un hospital de alta complejidad en Cali (Colombia). Métodos: Se realizó un estudio de casos y controles en pacientes que consultaron por diarrea o la desarrollaron durante la hospitalización y que tuvieron un resultado positivo en la prueba de PCR para Clostridium difficile. Durante el 2012 a 2014, se incluyeron 29 casos y 58 controles. Resultados: La prevalencia de Clostridium difficile hospitalaria en la institución fue de 10 por 10.000 pacientes hospitalizados; en 3 casos se identificó la cepa NAP1-027. Los factores relacionados a Clostridium difficile fueron la diabetes mellitus (OR = 7,4; IC 95%: 1,1-47,6; p = 0,035), la leucemia (OR: 4,1; IC 95%: 1,0-16,5; p =0,043) y el consumo de antibióticos por más de 7 días (OR = 7,0; IC 95%: 2,3-21,1; p = 0,001). Conclusión: Se confirmó la asociación entre el uso previo de antibióticos y la infección por Clostridium difficile, de acuerdo con lo reportado en la literatura mundial. Este estudio describe por primera vez en nuestro país la cepa hipervirulenta NAP1/O27 en pacientes hospitalizados.

Objectives: To estimate the prevalence and factors related to infection by Clostridium difficile in a high complexity hospital in Cali, Colombia. Methods: A case and control study was conducted in patients consulting for diarrhea or diarrhea developed during hospitalisation with a positive CRP test result for Clostridium difficile. During 2012-2014, 29 cases and 58 controls were included. Results: The prevalence of Clostridium difficile in the hospital was 10 per 10.000 hospitalised patients, in 3 cases the NAP1/O27 strain was identified. Factors associatedwith Clostridium difficile were diabetes mellitus (OR = 7.4, IC95%: 1.1-47.6, P=.035), leukaemia (OR: 4.1, IC95%: 1,0-16.5, P=.043) and consumption of antibiotics for more than 7 days (OR = 7.0, IC95%: 2,3-21.1, P=.001). Conclusions: This study confirmed the association of Clostridium difficile infection with the use of previous antibiotics, in accordance with that reported in literature. This study describes for the first time in our country the hypervirulent NAP1/O27 in hospitalised patients.

Analysis of risk factors and clinical manifestations associated with Clostridium difficile disease in Serbian hospitalized patients

Abstract Clostridium difficile is the leading cause of infectious diarrhoea in hospitalized patients. The aim of this study was to determine the risk factors important for the development of hospital-acquired Clostridium difficile-associated disease and clinical manifestations of Clostridium difficile-associated disease. The clinical trial group included 37 hospitalized patients who were selected according to the inclusion criteria. A control group of 74 hospitalized patients was individually matched with cases based on hospital, age (within 4 years), sex and month of admission.Clostridium difficile-associated disease most commonly manifested as diarrhoea (56.76%) and colitis (32%), while in 8.11% of patients, it was diagnosed as pseudomembranous colitis, and in one patient, it was diagnosed as fulminant colitis. Statistically significant associations (p < 0.05) were found with the presence of chronic renal failure, chronic obstructive pulmonary disease, cerebrovascular accident (stroke) and haemodialysis. In this study, it was confirmed that all the groups of antibiotics, except for tetracycline and trimethoprim-sulfamethoxazole, were statistically significant risk factors for Clostridium difficile-associated disease (p < 0.05). However, it was difficult to determine the individual role of antibiotics in the development of Clostridium difficile-associated disease. Univariate logistic regression also found that applying antibiotic therapy, the duration of antibiotic therapy, administration of two or more antibiotics to treat infections, administering laxatives and the total number of days spent in the hospital significantly affected the onset of Clostridium difficile-associated disease (p < 0.05), and associations were confirmed using the multivariate model for the application of antibiotic therapy (p = 0.001), duration of antibiotic treatment (p = 0.01), use of laxatives (p = 0.01) and total number of days spent in the hospital (p = 0.001). In this study of patients with hospital-acquired diarrhoea, several risk factors for the development of Clostridium difficile-associated disease were identified.

Clostridium difficile outbreak caused by NAP1/BI/027 strain and non-027 strains in a Mexican hospital

Abstract Background Clostridium difficile infections caused by the NAP1/B1/027 strain are more severe, difficult to treat, and frequently associated with relapses. Methods A case–control study was designed to examine a C. difficileinfection (CDI) outbreak over a 12-month period in a Mexican hospital. The diagnosis of toxigenic CDI was confirmed by real-time polymerase chain reaction, PCR (Cepheid Xpert C. difficile/Epi). Results During the study period, 288 adult patients were evaluated and 79 (27.4%) patients had confirmed CDI (PCR positive). C. difficilestrain NAP1/B1/027 was identified in 31 (39%) of the patients with confirmed CDI (240 controls were included). Significant risk factors for CDI included any underlying disease (p < 0.001), prior hospitalization (p < 0.001), and antibiotic (p < 0.050) or steroid (p < 0.001) use. Laboratory abnormalities included leukocytosis (p < 0.001) and low serum albumin levels (p < 0.002). Attributable mortality was 5%. Relapses occurred in 10% of patients. Risk factors for C. difficileNAP1/B1/027 strain infections included prior use of quinolones (p < 0.03). Risk factors for CDI caused by non-027 strains included chronic cardiac disease (p < 0.05), chronic renal disease (p < 0.009), and elevated serum creatinine levels (p < 0.003). Deaths and relapses were most frequent in the 027 group (10% and 19%, respectively). Conclusions C. difficile NAP1/BI/027 strain and non-027 strains are established pathogens in our hospital. Accordingly, surveillance ofC. difficile infections is now part of our nosocomial prevention program.

High occurrence of Fusobacterium nucleatum and Clostridium difficile in the intestinal microbiota of colorectal carcinoma patients

Abstract Colorectal carcinoma is considered the fourth leading cause of cancer deaths worldwide. Several microorganisms have been associated with carcinogenesis, including Enterococcus spp., Helicobacter pylori, enterotoxigenic Bacteroides fragilis, pathogenic E. coli strains and oral Fusobacterium. Here we qualitatively and quantitatively evaluated the presence of oral and intestinal microorganisms in the fecal microbiota of colorectal cancer patients and healthy controls. Seventeen patients (between 49 and 70 years-old) visiting the Cancer Institute of the Sao Paulo State were selected, 7 of whom were diagnosed with colorectal carcinoma. Bacterial detection was performed by qRT-PCR. Although all of the tested bacteria were detected in the majority of the fecal samples, quantitative differences between the Cancer Group and healthy controls were detected only for F. nucleatum and C. difficile. The three tested oral microorganisms were frequently observed, suggesting a need for furthers studies into a potential role for these bacteria during colorectal carcinoma pathogenesis. Despite the small number of patients included in this study, we were able to detect significantly more F. nucleatum and C. difficile in the Cancer Group patients compared to healthy controls, suggesting a possible role of these bacteria in colon carcinogenesis. This finding should be considered when screening for colorectal cancer.

Descripción clínica y epidemiológica de la infección por Clostridium difficile en población pediátrica / Clinic and epidemiologic description of Clostridium difficile infection in a pediatric population

Background: Clostridium difficile (CUj-associated disease (CDAD) and the role of the hypervirulent strain NAP1 have not been well characterized in Pediatrics. Aims: To describe clinical features of CDAD, and to estimate NAP1 frequency and association with disease severity in Pediatrics. Methods: Descriptive, transversal surveillance of diarrheal episodes in Chilean children, hospitalized between February 2012 and December 2013, positive for CD by molecular diagnosis. Results: A total of 66 episodes of diarrhea with identification of CD occurred thougout the study period in children between 1 month and 19 years of age of which 39% were younger than one year old. CD acquisition was predominantly nosocomial and the most common risk factors were: presence of comorbidities (98.6%), use of antibiotics (93.9%), proton pump inhibitors (84.8%), invasive mechanic ventilation (54.5%), feeding tube (48.5%) and immunosuppression (40.9%). Clinical course was mostly mild, but 12 cases presented an unfavorable course, of which 3/26 occurred in children less than one year. Only one case was positive for NAP1 and had a mild course. Conclusion: Diarrhea with identification of CD was present throughout all pediatric ages, including children less than one year old. Analytical and longitudinal studies are required to better characterize the pathogenic role of CD in this age group. CDAD occurred mostly in patients with risk factors, and the clinical course was predominantly mild.

Introducción: Aún no ha sido bien caracterizada la infección por Clostridium difficile ni el rol de la cepa hipervirulenta NAP1 en pediatría. Objetivos: Describir las características clínicas de la infección por C. difficile, la frecuencia de NAP1 y su asociación con gravedad en población pediátrica. Material y Método: Estudio transversal, descriptivo, de episodios de diarrea con identificación molecular de C. difficile en niños chilenos hospitalizados entre febrero de 2012 y diciembre de 2013. Resultados: Se estudiaron 66 episodios de diarrea por C. difficile, en niños entre 1 mes y 19 años, teniendo 39% menos de un año de edad. La adquisición fue predominantemente nosocomial. Los factores de riesgo más frecuentes fueron: co-morbilidades, uso de antimicrobianos, inhibidores de bomba de protones, ventilación mecánica invasora, sonda de alimentación e inmunosupresión. El curso clínico fue mayoritariamente benigno, con 12 casos de evolución desfavorable incluyendo lactantes bajo un año de edad. Un niño presentó la cepa NAP1, con un curso clínico leve. Discusión: En esta serie, la diarrea con identificación de C. difficile se presentó en niños de todas las edades, incluyendo aquellos bajo un año. Se necesitan estudios analíticos y longitudinales para determinar el rol patógeno en este último grupo etario. La infección afecta a niños con factores de riesgo y es de evolución predominantemente satisfactoria.

Diarrea asociada a Clostridium difficile en niños / Clostridium difficile associated diarrhea in children

Introduction: Clostridium difficile is the most commonly isolated organism in antimicrobial and health care-associated diarrhea and is growing in relevance in community-acquired infections. It is a Gram-positive bacillus acquired via the fecal-oral route in the community and in hospital setting. Epidemiology: 0.6 to 2.1% worldwide incidence, mortality ~ 1-5%. Colonization: High rates of asymptomatic colonization in healthy people, 37% in children: its presence in stools is of controversial significance. Risk factors in children are prior exposure to antibiotics, recent hospitalization, immunosuppression or inflammatory bowel disease. Clinical manifestations: secondary to intestinal involvement due to toxin production, ranging from asymptomatic colonization to fulminant disease. Diagnosis: Clinical diagnostic criteria plus high sensitivity and specificity laboratory certification. Recommendations AAP (American Academy of Pediatrics): under 1 year, avoid routine study, only in Hirschsprung disease and/or nosocomial outbreak, 1-3 year, a (+) result suggests C. difficile associated diarrhea (CDAD) is possible, and in children older than 3 years interpretation is equal to adults. Management: antimicrobial suspension, oral metronidazole as first line in mild to moderate CDAD, and oral or enema vancomycin or associated with intravenous metronidazole only in severe cases. Duration 10 days. Prevention: Antimicrobial control programs and environmental management. Conclusion: Given the increasing complexity of pediatric patients it is important to deepen the knowledge on this microorganism and its clinical manifestations, as its incidence, morbidity and mortality are increasing.

Introducción: Clostridium difficile, microorganismo más común en diarrea asociada a antimicrobianos, a atención de salud y en aumento en la comunidad es un bacilo grampositivo adquirido vía fecal oral en la comunidad y en el ambiente hospitalario. Epidemiología: Incidencia mundial 0,6-2,1%, mortalidad~1-5%. Colonización: Alta colonización asintomática en personas sanas, niños 37%, su presencia en las deposiciones es controversial. Factores de riesgo en niños: exposición previa a antimicrobianos, hospitalización reciente, inmunosupresión o enfermedad inflamatoria intestinal. Clínica: Compromiso intestinal secundario a la producción de toxinas. Puede variar desde una colonización asintomática hasta enfermedad fulminante. Diagnóstico: La certificación diagnóstica requiere de un criterio clínico más laboratorio rápido, con elevada sensibilidad y especificidad. Recomendaciones de American Academy of Pediatrics son en lactantes bajo un año, evitar estudio rutinario, sólo enfermedad de Hirschprung y/o brote nosocomial, entre 1-3 años; un resultado (+) indica DACD posible y en mayores de 3 años los criterios son igual a adultos. Manejo: Suspensión de antimicrobianos, metronidazol ev como primera línea en niños con DACD leve a moderada y vancomicina oral, enema o asociada a metronidazol intravenoso sólo en casos graves. Duración 10 días. Prevención: Control de antimicrobianos y manejo ambiental. Conclusión: Dada la creciente complejidad de pacientes pediátricos, es importante profundizar sobre este microorganismo y el desarrollo de enfermedad, ya que su incidencia y morbi-mortalidad van en aumento.

Current advances related to Clostridium difficile infection.

Clostridium difficile infection (CDI) can trigger various responses, ranging from asymptomatic carriage to fulminant colitis. Hard-to-cure CDI, such as severe CDI, multiple recurrences of CDI, refractory CDI, and hypervirulent strains of C. difficile, require new treatments, although antibiotics such as metronidazole and vancomycin are the treatment of choice for initial and first relapsing CDI. Active immunization with C. difficile toxins and faecal microbiota transplantation deserve special attention. Here we describe these strategies for difficult-to-treat CDI.

Epidemiology of Clostridium difficile: a hospital-based descriptive study in Argentina and Mexico

A prospective study was conducted in four tertiary hospitals in Argentina and Mexico in order to describe the occurrence of Clostridium difficile infection (CDI) in these settings. The objective was to evaluate the incidence of CDI in at-risk populations in Argentina (one center) and Mexico (three centers) and to further explore potential study sites for vaccine development in this region. A prospective, descriptive, CDI surveillance study was conducted among hospitalized patients aged ≥40 years who had received ≥48 h of antibiotic treatment. Stool samples were collected from those with diarrhea within 30 days after starting antibiotics and analyzed for toxins A and B by ELISA, and positive samples were further tested by toxinogenic culture and restriction endonuclease analysis type assay. Overall, 466 patients were enrolled (193 in Argentina and 273 in Mexico) of whom 414 completed the follow-up. Of these, 15/414 (3.6%) experienced CDI episodes occurring on average 18.1 days after admission to hospital and 15.9 days after the end of antibiotics treatment. The incidence rate of CDI was 3.1 (95% CI 1.7-5.2) per 1000 patient-days during hospitalization, and 1.1 (95% CI 0.6-1.8) per 1000 patient-days during the 30-day follow-up period. This study highlighted the need for further evaluation of the burden of CDI in both countries, including the cases occurring after discharge from hospital.