Trasplante de microbiota fecal por colonoscopía en paciente mayor de 65 años con infección recurrente de Clostridioides difficile: aún una estrategia subutilizada / Fecal microbiota transplantation in an older patient with Clostridioides difficile recurrent infection. Report of one case

Clostridioides difficile infection (CDI) is a major public health problem and responsible for significant morbidity and mortality. Eighty percent of CDIs occur in adults older than 65 years of age due to a decreased gastrointestinal microbial diversity, immunosenescence and frailty. Thus, the most reported risk factor for recurrent CDI is older age since nearly 60% of cases occur in individuals aged ≥ 65 years. Fecal microbiota transplantation (FMT) is a highly cost-effective alternative to antibiotic treatment for patients with recurrent CDI. We report a 75-year-old male with recurrent CDI, who received a FMT after several unsuccessful antimicrobial treatments. He had a satisfactory evolution after the procedure and remained without diarrhea during the ensuing five months.

In Silico Screening of DNA Gyrase B Potent Flavonoids for the Treatment of Clostridium difficile Infection from PhytoHub Database

Abstract Clostridium difficile infection (CDI) is the most common hospital acquired diarrheal disease with its increasing incidence and mortality rate globally. DNA Gyrase B (GyrB) is a key component of DNA replication process across all bacterial genera; thus, this offers a potential target for the treatment of CDI. In the present study, several virtual screening approaches were employed to identify a novel C. difficile GyrB inhibitor. The 139 known metabolites were screened out from the 480 flavonoids in PhytoHub database. Molinspiration and PROTOX II servers were used to calculate the ADME properties and oral toxicity of the metabolites, whereas mutagenicity, tumorigenicity, irritant, and reproductive effect were predicted using DataWarrior program. The binding mode and the binding efficiency of the screened flavonoids against the GyrB were studied using FlexX docking program. From virtual screening of 139 metabolites, we found 25 flavonoids with no mutagenicity, tumorigenicity, irritant, and reproductive effect. Docking study suggested that flavonoids 1030 ((-)-epicatechin 3'-O-sulfate), 1032 ((-)-epicatechin 4'-O-sulfate), 1049 (3'-O-methyl-(-)-epicatechin 4-O-sulfate), 1051 (3'-O-methyl-(-)-epicatechin 7-O-sulfate), 1055 (4'-O-methyl-(-)-epicatechin 7-O-sulfate) and 1317 (quercetin sulfate) have significantly higher binding affinity than the known GyrB inhibitor novobiocin. The results from molecular dynamics simulation and free energy calculations based on solvated interaction energy suggested that (-)-epicatechin 3'-O-sulfate could be a potential drug candidate in the management of CDI.

Trasplante de microbiota fecal en la infección por Clostridioides difficile / Faecal microbiota transplantation for Clostridioides difficile infection

Resumen La infección por Clostridioides difficile (iCD) es la causa más frecuente de diarrea nosocomial. La primera línea terapéutica es la vancomicina asociada o no al metronidazol. En los últimos años se incrementó el número de fracasos terapéuticos con una mayor frecuencia de formas refractarias o recurrentes. El trasplante de microbiota fecal (TMF) ha surgido como una opción terapéutica para estos casos. Se evaluó la seguridad y la tasa de resolución empleando el TMF en un estudio observacional abierto y prospectivo de 21 pacientes con iCD recurrentes o refractarias internados entre los años 2016 y 2019. La edad media fue de 76.5 años (33-92). Diez presentaron una forma recurrente y 11 una refractaria, 18 fueron graves y 3 fulminantes. En 20 casos el TMF se administró por la vía digestiva alta y en uno por presentar íleo se utilizó la vía baja. Se empleó TMF de heces frescas en un caso y el resto recibió muestras congeladas de un banco de microbiota. Veinte pacientes (95.2%) tuvieron respuesta terapéutica favorable sin presentar recurrencias. Un caso recurrente, con osteomielitis y falla multiorgánica, no tuvo resolución tras dos TMF. La respuesta fue similar en las formas recurrentes y refractarias. Siete pacientes (31%) tuvieron efectos adversos leves y autolimitados. El TMF ha demostrado una alta eficacia como tratamiento de rescate de las formas graves de iCD, con escasos y leves efectos adversos. Contar con un banco de microbiota fecal resulta fundamental para disponer de este recurso terapéutico oportunamente.

Abstract Clostridiodes difficile infection (CDi) is the most common cause of nosocomial diarrhea. Vancomycin, associated or not to metronidazol, is the treatment of choice. However, the rate of treatment failure has increased over the last years and fecal microbiota transplantation (FMT) has emerged as a therapeutic option. To evaluate safety and efficacy of FMT were enrolled 21 hospitalized patients with refractory or recurrent CDi between 2016 and 2019. Fourteen (66%) patients were men and the average age was 76.5 years (range 33-92). Ten had recurrent and 11 refractory CDi, and 18 presented severe and 3 fulminant clinical forms. In 20 cases the FMT was delivered through a nasojejunal tube and in one patient with ileo via enema infusion. Frozen fecal from a stool bank were administered in 20 and in the remaining was used fresh fecal matter. The rate of resolution was observed in 20 patients (95.2%) and none presented recurrence. The response rate was similar in recurrent or refractory forms (9/10 vs 11/11 respectively). One patient with osteomyelitis and multiple organ failure received 2 FMT without response and died. Seven patients (31%) presented mild and self-limited adverse effects. FMT has shown a high efficacy as rescue treatment in cases with refractory or recurrent CDi regardless of severity, with mild side effects. Availability of a stool banks provide reliable, timely and equitable access to FMT for CDi.

Estruturação de centro de transplante de microbiota fecal em hospital universitário no Brasil / Structuring a fecal microbiota transplantation center in a university hospital in brazil

ABSTRACT BACKGROUND: Fecal microbiota transplantation (FMT) is an important therapeutic option for recurrent or refractory Clostridioides difficile infection, being a safe and effective method. Initial results suggest that FMT also plays an important role in other conditions whose pathogenesis involves alteration of the intestinal microbiota. However, its systematized use is not widespread, especially in Brazil. In the last decade, multiple reports and several cases emerged using different protocols for FMT, without standardization of methods and with variable response rates. In Brazil, few isolated cases of FMT have been reported without the implantation of a Fecal Microbiota Transplantation Center (FMTC). OBJECTIVE: The main objective of this study is to describe the process of implanting a FMTC with a stool bank, in a Brazilian university hospital for treatment of recurrent and refractory C. difficile infection. METHODS: The center was structured within the criteria required by international organizations such as the Food and Drug Administration, the European Fecal Microbiota Transplant Group and in line with national epidemiological and regulatory aspects. RESULTS: A whole platform involved in structuring a transplant center with stool bank was established. The criteria for donor selection, processing and storage of samples, handling of recipients before and after the procedure, routes of administration, short and long-term follow-up of transplant patients were determined. Donor selection was conducted in three stages: pre-screening, clinical evaluation and laboratory screening. Most of the candidates were excluded in the first (75.4%) and second stage (72.7%). The main clinical exclusion criteria were: recent acute diarrhea, overweight (body mass index ≥25 kg/m2) and chronic gastrointestinal disorders. Four of the 134 candidates were selected after full screening, with a donor detection rate of 3%. CONCLUSION: The implantation of a transplant center, unprecedented in our country, allows the access of patients with recurrent or refractory C. difficile infection to innovative, safe treatment, with a high success rate and little available in Brazil. Proper selection of qualified donors is vital in the process of implementing a FMTC. The rigorous clinical evaluation of donors allowed the rational use of resources. A transplant center enables treatment on demand, on a larger scale, less personalized, with more security and traceability. This protocol provides subsidies for conducting FMT in emerging countries.

RESUMO CONTEXTO: O Transplante de microbiota fecal (TMF) é uma importante opção terapêutica para a infecção recorrente ou refratária pelo Clostridioides difficile, sendo método seguro e eficaz. Resultados iniciais sugerem que o TMF também desempenha papel relevante em outras afecções cuja patogênese envolve a alteração da microbiota intestinal. No entanto, seu uso sistematizado é pouco difundido, especialmente no Brasil. Na última década, surgiram múltiplos relatos e séries de casos utilizando diferentes protocolos para o TMF, sem padronização de métodos e com taxas de resposta variáveis. No Brasil, poucos casos isolados de TMF foram relatados sem a implantação de um Centro de Transplante de Microbiota Fecal (CTMF). OBJETIVO: O principal objetivo deste estudo foi descrever o processo de implantação de um CTMF com banco de fezes, em hospital universitário brasileiro, para tratamento de infecção recorrente e refratária pelo C. difficile. MÉTODOS: O CTMF foi estruturado dentro dos critérios exigidos e aprovados por organismos internacionais como o Food and Drug Administration, Grupo Europeu de Transplante de Microbiota Fecal e em consonância com os aspectos epidemiológicos e regulatórios nacionais. RESULTADOS: Foi estabelecida toda uma plataforma envolvida na estruturação de um centro de transplante com fezes congeladas. Determinou-se os critérios para seleção de doadores, processamento e armazenamento de amostras, manejo dos receptores antes e após o procedimento, uniformização de vias de administração do substrato fecal e seguimento a curto e longo prazo dos pacientes transplantados. A seleção dos doadores foi conduzida em três etapas: pré-triagem, avaliação clínica e exames laboratoriais. Boa parte dos candidatos foram excluídos na primeira (75,4%) e segunda etapa (72,7%). Os principais critérios clínicos de exclusão foram: diarreia aguda recente, excesso de peso (IMC ≥25 kg/m2) e distúrbios gastrointestinais crônicos. Quatro dos 134 candidatos foram selecionados após a triagem completa, com taxa de detecção de doadores de 3%. CONCLUSÃO: A implantação de um CTMF, inédito no nosso meio, possibilita o acesso de pacientes com infecção recorrente e refratária pelo C. difficile a tratamento inovador, seguro, com elevada taxa de sucesso e pouco disponível no Brasil. A seleção apropriada de doadores qualificados é vital no processo de implantação de um CTMF. A avaliação clínica rigorosa dos doadores permitiu o uso racional de recursos para realização de exames laboratoriais. Um CTMF possibilita tratamento sob demanda, em maior escala, menos personalizados, com mais segurança e rastreabilidade. Este protocolo fornece subsídios para a realização de TMF em países emergentes.

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)

Trasplante de materia fecal en pacientes octogenarios con infección recurrente por Clostridioides difficile / Transplantation of fecal matter in octogenarian patients with recurrent Clostridioides difficile infection

Resumen La infección por Clostridioides (previamente Clostridium) difficile se ha convertido en un problema de salud importante debido al aumento en su incidencia, gravedad y recurrencia. En este último escenario, una edad mayor de 65 años ha sido asociada a una evolución más desfavorable. Factores de riesgo como la presencia de una inmunidad alterada, co-morbilidades, malnutrición, polifarmacia y cambios en la microbiota intestinal explicarían este mayor riesgo a mayor edad. El trasplante de microbiota fecal (TMF) es una estrategia efectiva en el tratamiento de la infección recurrente por Clostridioides difficile cuando la terapia estándar fracasa. Guías publicadas recientemente sugieren que esta estrategia puede ser utilizada a partir de la segunda recurrencia. Sin embargo, escasos estudios han evaluado los resultados del TMF en pacientes mayores de 65 años y para nuestro conocimiento existe una escasa experiencia nacional en este grupo de pacientes. Presentamos dos casos de TMF en pacientes octogenarios con una infección recurrente por Clostridioides difficile, con una evolución satisfactoria a largo plazo.

Clostridioides (formerly Clostridium) difficile infection has become a major health problem due to the increase in its incidence, severity, and recurrence. In this last scenario, age over 65 has been associated with a more unfavorable evolution. Risk factors such as the presence of altered immunity, comorbidities, malnutrition, polypharmacy, and changes in the intestinal microbiota would explain this higher risk in this group of patients. On the other hand, fecal microbiota transplantation (FMT) is an effective strategy in the treatment of recurrent Clostridioides difficile infection when standard therapy fails. Recently published guidelines suggest that this strategy can be used from the second recurrence. However, few studies have evaluated the results of the FMT in patients over 65 years old, and for our knowledge, there is limited national experience in this group of patients. We present two cases of TMF in octogenarian patients with a recurrent infection due to Clostridioides difficile, with satisfactory recovery at the long term.

Colitis refractaria por Clostridium difficile tratada con trasplante de microbiota fecal / Refractory colitis by Clostridium difficile treated with fecal microbiota transplant

La diarrea por Clostridium difficile es reconocida de manera creciente en pacientes hospitalizados y se asocia con alta mortalidad. La vancomicina por vía enteral es el tratamiento antibiótico recomendado para las diferentes formas, incluso las más graves. Sin embargo, un grupo pequeño de pacientes desarrolla formas refractarias a ese tratamiento y no existen esquemas antibióticos alternativos recomendados para estos casos. El trasplante de microbiota fecal ha demostrado ser exitoso en una serie de casos de diarrea grave asociada a este microorganismo. Presentamos un caso de diarrea refractaria por C. difficile que fue tratada con éxito con una infusión de microbiota fecal.

Clostridium difficile infection is an increasingly recognized cause of diarrhea in inpatients, frequently associated to high mortality. Vancomycin is the treatment of choice for all Clostridium difficile- associated diarrheas, with different degrees of severity. However, some patients develop refractory forms to that treatment and there are no alternative antibiotic schemes recommended for these cases. Fecal microbiota transplantation has been shown to be successful in a series of cases of severe diarrhea associated with this organism. We present a case of refractory C. difficile infection successfully treated with fecal microbiota transplantation.

Experiencia del trasplante de microbiota fecal a través de colonoscopía en el tratamiento de la infección por Clostridium difficile recurrente / Fecal microbiota transplantation through colonoscopy for Clostridium difficile recurrent infection: report of eight cases

Background: Most cases of Clostridium difficile infection (CDI) respond to a standard course of antibiotics, however recurrent CDI is becoming common and alternative therapeutic strategies are needed. In this scenario, fecal microbiota transplantation (FMT) has been suggested. Aim: To describe the efficacy and safety of FMT for the treatment of recurrent CDI. Patients and Methods: Review of medical records of all patients with recurrent CDI treated with FMT between April 2013 and April 2017. Demographic and clinical data were abstracted including details of treatment prior to FMT, rate of FMT treatment success and clinical course during follow-up period. Telephone surveys were conducted to determine patient satisfaction. Results: Eight patients aged 19 to 82 years (six women) underwent FMT. They experienced a median of four previous episodes of CDI (range 3-8). The mean duration of CDI was 18 days (range 3-36) before FMT. All procedures were performed by colonoscopy. Effectiveness with one session of FMT was 100%. During the follow-up period (median 24 months, range 7-55), two patients developed CDI, one of them after using antibiotics. Adverse events were reported in three patients. Two had bloating and one patient with Crohn's disease and a history of bacteremia had an episode of Escherichia coli bacteremia. All patients would use FMT again if necessary. Conclusions: FMT through colonoscopy appears to be a safe, effective and long-lasting therapy in cases of recurrent CDI.

Claves prácticas para un trasplante de microbiota fecal por colonoscopía en infección por Clostridium difficile recurrente. Experiencia en un centro universitario / Practical clues for a fecal microbiota transplantation by colonoscopy for recurrent Clostridium difficile infection. Experience in a University center

Resumen El trasplante de microbiota fecal (TMF) constituye una terapia altamente eficaz en la infección por Clostridium difficile (ICD) recurrente. La mejor vía de administración del material fecal aún no ha sido establecida; sin embargo, la vía baja a través de colonoscopía resulta eficaz, segura y de mayor aceptación por los pacientes, permitiendo además el examen de la mucosa del colon en busca de diagnósticos diferenciales. Presentamos una serie de casos de TMF realizados en nuestra institución a través de colonoscopía, destacando los resultados y aspectos prácticos para su implementación.

Fecal microbiota transplantation (FMT) is a highly effective therapy in recurrent Clostridium difficile. The best route to administrate the fecal matter has not been established yet. However, the lower gastrointestinal route by colonoscopy is effective and safe, presenting a higher acceptance by patients. In addition, this route allows an evaluation of colonic mucosa seeking for differential diagnostics. We present a case series of FMT performed in our institution by colonoscopy, highlighting outcomes and practical aspects for its implementation.

Trasplante de microbiota fecal en infección recurrente por Clostridium difficile: Experiencia local a partir de un caso clínico / Fecal microbiota transplantation in recurrent Clostridium difficile infection: Report of one case

Fecal microbiota transplantation (FMT) has an incomparable efficacy to treat recurrent Clostridium difficile infection, with near 90% of success. We report a 57 years old woman who developed an antibiotic associated diarrhea with a positive polymerase chain reaction test for Clostridium Difficile toxin. She was successfully treated with Vancomycin trice but diarrhea recurred. Therefore a fecal microbiota transplant was performed using solid stools from a relative, diluted in saline and instilled in the distal ileon, with a good clinical response, without recurrence of diarrhea, during a 6-month follow-up.

Trasplante de microbiota fecal: primer caso reportado en Chile y revisión de la literatura / Fecal microbiota transplantation: first case report in Chile and review

Clostridium difficile (CD) infection is increasing in frequency and severity in in-hospital and outpatient clinical settings, with a recurrence that can reach 30% after first episode. The recurrences are usually treated with longer courses of metronidazole or vancomycin. Other treatments have been used, such as probiotics, fidaxomicin, rifaximin, immunoglobulins and monoclonal antibodies against toxins A and B. Fecal microbiota transplantation (FMT) has emerged as a promising strategy in this group of patients, with effectiveness greater than 90%. We present the first case reported in Chile of this therapeutic strategy in a patient with Crohn's disease and recurrent CD infection who presented after the fecal transplantation an Escherichia coli bacteremia, suggesting the need for caution in the use of this strategy. 10 months after the FMT the patient presented a new episode of E. coli bacteremia and two episodes of diarrhea due to CD infection, treated both of them with vancomycin with good clinical response.

La infección por Clostridium difficile (CD) está aumentando en frecuencia y gravedad tanto a nivel intrahospitalario como ambulatorio, con una recurrencia que puede alcanzar hasta 30% después de un primer episodio. Los cuadros recurrentes son generalmente tratados con cursos prolongados de metronidazol y/o vancomicina. Otras terapias han sido sugeridas como el uso de probióticos, fidaxomicina, rifaximina, inmunoglobulina y anticuerpos monoclonales para toxina A y B. El trasplante de microbiota fecal (TMF) ha emergido como una estrategia promisoria en este grupo de pacientes con una efectividad mayor a 90%. Presentamos el primer caso reportado en Chile de esta estrategia terapéutica en un paciente con enfermedad de Crohn y CD recurrente, quien presentó una bacteriemia por Escherichia coli post-TMF, sugiriendo la necesidad de tener precaución con el uso de esta estrategia. El paciente presentó a los 10 meses post-TMF un nuevo episodio de bacteriemia por E. coli y dos episodios de diarrea por CD siendo tratados ambos cuadros con vancomicina con buena respuesta clínica.

Manejo de la infección por Clostridium difficile, a propósito de un caso complejo / Management of Clostridium difficile infection, in relation to a complex case

Clostridium difficile diarrhea is one of the most important health care–related infections in the world, and is associated with significant morbidity and mortality with high economic costs. Treatment consists basically on the use of antibiotics. Metronidazole is the first-line agent. Vancomycin is reserved for more serious cases, or for patients who do not respond to treatment with metronidazole; however, there is a significant percentage of patients that can be refractory to the initial treatment or can have recurrences. For these cases a treatment option is fidaxomicin, but its use is limited due to high costs. In this context, an alternative treatment option is fecal transplant, which has proven to be highly effective in treatment of recurrent condition nonresponsive to traditional management. We present a case of a young female patient with a chronic renal failure in hemodialysis, with chronic diarrhea due to Clostridium difficile. This patient was treated at a public health facility in the south of Chile; in a site with difficult access to complex diagnostic techniques and new treatments. After non-response to management with traditional antibiotics and several months with diarrhea; the fecal transplantation was perform with a rapid and symptomatic improvement.

La diarrea por Clostridium difficile es una de las infecciones asociadas a atención en salud más importantes a nivel mundial, y está asociada a importante morbimortalidad y a elevados costos económicos. El tratamiento se basa en el uso de antibióticos, para lo que se utiliza metronidazol como agente de primera línea, y vancomicina, que se reserva para casos más graves, o pacientes que no responden al tratamiento con metronidazol; no obstante, existe un importante porcentaje de pacientes que pueden ser refractarios al tratamiento inicial o tener recurrencias. Para estos casos una opción de tratamiento es fidaxomicina, sin embargo, su uso está limitado por su elevado costo. En este contexto surge como alternativa el trasplante fecal, nueva alternativa que ha probado ser altamente eficaz en tratamientos de recidivas que no responden al manejo tradicional. A continuación se describe el caso de una paciente joven portadora de insuficiencia renal crónica en hemodiálisis, con diarrea crónica por Clostridium difficile, tratada en un centro del sistema público de salud del sur de Chile, centro con dificultades tanto para acceder a técnicas diagnósticas complejas, como a tratamientos de última generación. Luego de no responder al manejo antibiótico tradicional, tras meses con diarrea crónica, es sometida a trasplante fecal con rápida mejoría sintomática.

Trasplante de microbiota fecal en paciente con colitis ulcerosa e infección refractaria por: revisión de la literatura a partir de un caso clínico / Fecal microbiota transplantation in patient with ulcerative colitis and refractory infection due to: review of the literature based on a clinical case

Infection (CDI) is increasing both in the hospital environment as in the outpatient setting, and is associated with prior use of antibiotics, hospitalizations and inflammatory bowel disease (IBD), among others. It is also characterized by a high rate of recurrence with the usual antibiotic treatment, which increases with greater number of episodes, reaching up to 65 percent. In this context, the transplantation of fecal microbiota (FMT) emerges as recurrent CDI therapy, achieving success rates exceeding 90 percent, including in IBD patients, with minimum rates of recurrence. To achieve such efficiency, the colonization by the donated microbiota in the recipient is critical. The role of FMT is still unclear in IBD therapy not associated with CDI. Although there are great differences in the methodology of FMT, the process has been standardized even creating banks of frozen fecal samples, without reducing its effectiveness. FMT is a safe procedure, without serious adverse events, and accepted by the potential beneficiary population. There are few reported cases of refractory CDI management with FMT. Since 2012, the FMT in CDI and IBD publications have increased significantly, but in our country there are only few reports of this therapeutic strategy. We present a patient with ulcerative colitis and conventional antimicrobial management resistant CDI, which was successfully treated with FMT in a public hospital in Chile.

La infección por Clostridium difficile (ICD) está en aumento tanto en el ambiente hospitalario como ambulatorio, y se asocia a uso previo de antibióticos, hospitalización y enfermedades inflamatorias intestinales (EII), entre otros. Se caracteriza además por su alta tasa de recurrencia con el tratamiento antimicrobiano habitual, que aumenta con el mayor número de episodios alcanzando hasta 65 por ciento. En este contexto, el trasplante de microbiota fecal (TMF) surge como terapia para la ICD recurrente, logrando tasas de éxito superiores a 90 por ciento, incluyendo pacientes con EII, con mínimas tasas de recurrencia. Para lograr esa eficacia, la colonización por la microbiota donada en el receptor es fundamental. Aún no está claro el rol del TMF en la terapia de EII no asociada a ICD. Aunque existe gran heterogeneidad en la metodología del TMF, el proceso se ha ido estandarizando incluso hasta llegar a la creación de bancos de muestra fecal congelada, sin disminuir su efectividad. El TMF es un procedimiento seguro, sin eventos adversos graves y aceptado por la población potencialmente beneficiaria de él. Existen pocos casos publicados de manejo de ICD refractaria con TMF. Desde el 2012 el número de publicaciones sobre TMF en ICD y en EII ha aumentado considerablemente, sin embargo, en nuestro país los reportes sobre esta estrategia terapéutica son escasos. Presentamos el caso de un paciente con colitis ulcerosa e ICD refractaria al manejo antimicrobiano habitual, que se trató exitosamente con TMF en un hospital público de Chile.

Infección por Clostridium difficile: enfrentamiento de la crisis grave y recurrencia / Clostridium difficile infection: management of severe and recurrent disease

Clostridium difficile has become an important healthcare-associated infection due to increased frequency, mortality and recurrence rate. These facts, associated in part to the appearance of epidemic strains have driven changes in diagnostic and therapeutic approaches. The clinical spectrum of C. difficile infection (CDI) ranges from mild diarrhea without systemic compromise to life-threatening pseudomembranous colitis. Metronidazole is the first line treatment in mild CDI; however, the response rate is lower in severe disease, therefore in patients with clinical markers of unfavorable outcome, the first line treatment is oral vancomicin. On the other hand, the increased recurrence rate seen in the last decade with its clinical and economic consequences has forced the development of new therapies that allow change the course of this disease. In this line, the fecal microbiota transplantation and new antibiotics as fidaxomicin has proved to decrease the recurrences.

Clostridium difficile es actualmente una de las principales infecciones asociadas a la atención de salud debido al aumento de su frecuencia, letalidad y capacidad de recurrencia. Estos hechos en parte asociados al surgimiento de cepas conocidas como epidémicas han determinado grandes cambios en el enfrentamiento diagnóstico y terapéutico. El espectro clínico de la infección por C. difficile (ICD) abarca desde una diarrea leve sin compromiso sistémico hasta cuadros de colitis pseudomembranosa que pueden ocasionar la muerte. Metronidazol es el tratamiento de elección de la ICD leve; sin embargo, la tasa de respuesta es inferior en cuadros graves, por lo tanto, en pacientes con marcadores de mal pronóstico vancomicina oral es la terapia de primera elección. Por otro lado, la mayor tasa de recurrencia observada en la última década con sus consecuencias clínicas y económicas ha obligado al desarrollo de nuevas terapias que permitan alterar el curso de la enfermedad. En esta línea, el trasplante de microbiota fecal y nuevos antibióticos como fidaxomicina han mostrado efectividad en reducir las recurrencias.

Colitis y trasplante de microflora intestinal: ¿cuándo plantearlo? / Colitis and fecal microbiota transplantation: who benefits?

The gastrointestinal microbiota acts as a metabolic organ that provides enzymatic pathways, contributes to the development and maintenance of local and systemic lymphoid organs, regulates the homeostasis of the intestinal epithelial barrier, modulates the systemic inflammatory and metabolic processes and activates the immune system, providing protection against bacterial and viral agents. Clostridium difficile diarrhea is the leading cause of nosocomial diarrhea with high morbidity and mortality rates. This occurs, among other causes, due to dysbiosis. Fecal microflora transplantation is an option, particularly in recurrent episodes. There are case reports on fecal microflora transplantation used for the treatment of inflammatory bowel disease, with promising results.

La microbiota gastrointestinal funciona como un órgano metabólico que provee de rutas enzimáticas no presentes en nuestro organismo; contribuye al desarrollo y mantenimiento de órganos linfoides locales y sistémicos, a la homeostasis de la barrera epitelial intestinal; modula los procesos inflamatorios sistémicos y metabólicos y activa el sistema inmunológico sitémico, brindando protección frente agresiones bacterianas y virales. La diarrea por Clostridium difficile es la principal causa de diarrea intrahospitalaria con una alta morbilidad y mortalidad. Esta se produce entre otras causas por una disbiosis. El trasplante de microflora fecal ha demostrado ser una opción terapéutica eficaz, especialmente en los episodios recurrentes. Existen reportes de casos con resultados promisorios en que se utiliza el trasplante de microflora fecal para el tratamiento de enfermedad inflamatoria intestinal crónica.

Clinical spectrum & pathogenesis of Clostridium difficile associated diseases.

Clostridium difficile is the major aetiological agent of antibiotic associated diarrhoea and colitis. The majority of hospitalized patients infected by C. difficile are asymptomatic carriers who serve as silent reservoirs for continued C. difficile contamination of the hospital environment. C. difficile associated disease (CDAD) is a serious condition with mortality up to 25 per cent in frail elderly people. C. difficile infection may present itself in several forms with both colonic and extracolonic manifestations. Several factors are involved in determining whether or not a patient develops C. difficile infection. These include factors related to the pathogen as well as the host. Transmission of C. difficile can be endogenous or exogenous. Colonization of the pathogen occurs when the gut flora gets disrupted due to various factors. The main virulence factors for CDAD are the two potent toxins: toxin A and toxin B which share 63 per cent of amino acid sequence homology and act on small guanosine triphosphate binding proteins. The emergence of the global hypervirulent C. difficile strain has been a cause of concern. Diagnosis of CDAD infection can be done by detection of C. difficile toxin in the stool specimen. Vancomycin is the drug of choice for severely ill patient, whereas metronidazole can be used for mild to moderately ill patients. Clinical spectrum, the factors precipitating CDAD, pathogenesis, diagnostic assay and treatment of the disease are reviewed.

Clostridial toxins - potent poisons, potent medicines

Clostridium is an anaerobic bacterial genus. The clostridia produce more protein toxins than any other bacterial genus and are a rich reservoir of toxins for research and medicinal uses. Clostridia are widely spread in the environment: soil, dust and water, presenting more than 120 described species, although few can cause diseases. Diseases can grossly be divided into neurotropic disorders (nervous system is primarily affected), enterotoxemias (affecting intestinal tract and parenchymatous organs), and gas gangrene (myonecrosis with toxemia). Undoubtedly the most widely recognized infection due to anaerobes was clostridial myonecrosis, but recently interest has arisen for the role of clostridia in intestinal diseases. This report describes the most important species, the diseases caused by them, and their occurrence in Brazil, focusing on cattle raising

Síndrome de mondor. Sepsis puerperal por clostridium perfringens: reporte de un caso / Mondor syndrome. Puerperal infections by clostridium perfringens: report of a case

La infección uterina por Clostridium perfringens es una enfermedad potencialmente fatal, poco frecuente en práctica obstétrica. Las manifestaciones de esta infección son variables en un rango que va desde la endometritis hasta la gangrena gaseosa y sepsis fulminante. Presentamos un caso de sepsis puerperal, su forma clínica, diagnóstico y aspectos terapéuticos