Actualización en el diagnóstico y manejo de la Infección por Clostridioides difficile / Update in diagnosis and management of Clostridioides difficile

El Clostridioides difficile (C. difficile) es una de las principales causas de infección asociada a la atención de salud con una elevada morbimortalidad, sobre todo en adultos mayores hospitalizados. El aumento en el uso de antibióticos ha ido de la mano con el incremento en el número de casos y de una mayor virulencia. Su presentación clínica va desde portadores asintomáticos hasta megacolon tóxico, escenarios que deben ser considerados al momento de realizar el estudio con exámenes de deposiciones (glutamato deshidrogenasa, toxinas A y B y técnicas de amplificación ácidos nucleares). Se han incorporado al arsenal terapéutico, con mayor nivel de evidencia, la fidaxomicina, trasplante microbiota fecal y recientemente nuevas terapias como anticuerpos monoclonales. Sin embargo, la gravedad de la infección, comorbilidad del paciente, presencia factores de recurrencia, el acceso y el costo económico de cada una de las opciones terapéuticas deben ser considerados. El objetivo de esta revisión es actualizar el manejo propuesto por las Sociedades Chilenas de Gastroenterología e Infectología publicadas el 2016 incorporando las últimas recomendaciones con respecto a prevención, diagnóstico y tratamiento de la infección por C. difficile.

Clostridioides difficile (C. difficile) is one of the leading causes of infection associated with health care with high morbidity and mortality, especially among hospitalized older adults. The increase in the use of antibiotics has been associated with a higher number of cases and greater virulence. Its clinical presentation ranges from asymptomatic carriers to toxic megacolon. Studies with stool tests (glutamate dehydrogenase, toxins A and B, and nuclear acid amplification techniques) should be considered in these cases. Fidaxomicin, fecal microbiota transplant, and new therapies such as monoclonal antibodies have been incorporated into the therapeutic arsenal, with a higher level of evidence. Nevertheless, the severity, patient comorbidity, recurrence risk factors, and the economic cost of each therapeutic option must be considered. This review aims to update the last guidelines proposed by the Chilean Societies of Gastroenterology and Infectious Diseases published in 2016, providing the latest recommendations regarding prevention, diagnosis, and treatment of C. difficile infection.

Trasplante de microbiota fecal por colonoscopía en una mujer embarazada con infección recurrente por Clostridioides difficile / Fecal microbiota transplantation through colonoscopy for Clostridioides difficile recurrent infection in a pregnant woman

El diagnóstico de la infección por Clostridioides dfficile (ICD) ha aumentado en el embarazo y periparto. Cambios fisiológicos e inmunológicos normales durante el embarazo pueden incrementar el riesgo de ICD. Mujeres embarazadas con ICD tienen una mayor frecuencia de fracaso al tratamiento y una significativa morbilidad y mortalidad. El trasplante de microbiota fecal (TMF) se ha convertido en el tratamiento estándar de la ICD recurrente y refractaria. Sin embargo, existen escasos datos sobre sus resultados en mujeres embarazadas. Presentamos el caso de una mujer embarazada que se sometió con éxito a un TMF para el tratamiento de una ICD recurrente.

The diagnosis of Clostridioides dfficile infection (CDI) in pregnant and peripartum women has increased. In this scenario, there are higher rates of treatment failure and a significant maternal morbidity and mortality. Fecal microbiota transplant (FMT) has become the gold standard for the treatment of recurrent and refractory CDI however, there are few data on its results in pregnant patients. This case showed that FMT could be a therapeutic strategy in pregnant women with recurrent CDI.

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.

Experience of a gastroenterology center in fecal microbiota transplantation in the treatment of Clostridioides Difficile / Experiência de um centro de gastroenterologia em transplante de microbiota fecal no tratamento de Clostridioides difficile

Background: The treatment of Clostridioides difficile is based on an antibiotics cycle, but for individuals who have more than two recurrences, fecal microbiota transplantation can be considered as a therapeutic option. Objective: To describe the technique and results of fecal microbiota transplantation performed for recurrent infection by Clostridioides difficile. Methods: Retrospective, cross-sectional study based on a review of medical records of patients undergoing transplantation of fecal microbiota. Data were obtained on the criteria used to select the donor, the preparation of stools in the laboratory and the method of delivery of the material offered, as well as information regarding the characteristics of the recipient, such as: gender, age, comorbidities, hospitalizations, use of antibiotics prior to infection, clinical presentation, diagnosis and treatments performed for Clostridioides difficile. After transplantation, data on efficacy, outcome, follow-up time and procedure complications were considered. Results: Between 2012 and 2019, 11 patients underwent fecal microbiota transplantation. The use of antibiotics prior to infection occurred in 9 patients, no patient was hospitalized in the previous 6 months due to another etiology. All had at least 2 cycles of vancomycin for recurrent disease. Of the total of 11 patients, 2 required 2 infusions and 1 patient required 3, totaling 15 fecal microbiota transplants. The success rate was 81.8% with only one infusion and 90.9% resolution considering patients who needed more than one infusion. Conclusion: Fecal microbiota transplantation is a feasible therapy with resolution in 90.9% of cases as a treatment for recurrent Clostridioides difficile infection.

Contexto: O tratamento do Clostridioides difficile é baseado em ciclo antimicrobiano, mas para os indivíduos que apresentam mais de duas recorrências, pode-se considerar o transplante de microbiota fecal como opção terapêutica. Objetivo: Descrever a técnica e os resultados do transplante de microbiota fecal realizados para infecção recorrente por Clostridioides difficile. Métodos: Estudo retrospectivo, transversal, baseado em revisão de prontuários de pacientes submetidos ao transplante de microbiota fecal. Foram obtidos dados sobre os critérios empregados para seleção do doador, o preparo das fezes e o método de entrega do material, além de informações referentes às características do receptor, como: sexo, idade, comorbidades, internamentos, uso de antimicrobiano prévio à infecção, apresentação clínica, diagnóstico e tratamentos realizados para o Clostridioides difficile. Após o transplante, dados sobre eficácia, desfecho, tempo de seguimento e complicações do procedimento foram considerados. Resultados: Entre 2012 e 2019, 11 pacientes foram submetidos ao transplante de microbiota fecal. O uso de antimicrobiano prévio à infecção ocorreu em 9 pacientes, nenhum paciente internou nos 6 meses anteriores por outra etiologia. Todos fizeram pelo menos 2 ciclos de vancomicina para doença recorrente. Do total de 11 pacientes, 2 necessitaram de 2 infusões e 1 paciente necessitou de 3, totalizando 15 transplantes de microbiota fecal. O sucesso foi de 81,8% com apenas uma infusão e resolução de 90,9% considerando pacientes que necessitaram de mais de uma infusão. Conclusão: O transplante de microbiota fecal é uma terapia factível e com resolução em 90,9% dos casos como tratamento de infecção recorrente por Clostridioides difficile.

The Effect of Stool Transplantation on Weight Control in Obese Rats / O efeito do transplante de fezes no controle de peso em ratos obesos

Abstract Introduction Obesity is defined as a multifactorial metabolic syndrome in which there is an excessive number of fat cells within the tissues. It is discussed that intestinal microbiota might have a relevant relation with obesity, since it is relevantly altered in obese patients. Objectives To assess the effect of stool transplantation (ST) in the condition of obesity and its outcomes in an experimental model of cafeteria diet by analyzing histology and weight gain. Methods Forty male Wistar rats were randomly assigned to 5 groups: control (CO), control with antibiotics (CO+ATB), obesity (CAF+ATB), stool transplantation (ATB+ ST) and obesity with stool transplantation (CAF+ATB+ST). During the experiment, obesity induction groups received cafeteria diet, whereas the remaining groups had normal diet ad libitum. After 3 months, daily ST was carried out for 8 weeks by gavage procedure. The animals were euthanized, and the small intestine was harvested for further analysis. Results It was observed that before starting the ST, the cafeteria and normal diet groups had significant weight difference (p<0,0001). In the comparison between CAF+ATB and CAF+ATB+ST during the gavage period, the CAF+ATB+ST group presented lower weight gain (p=0.0017). The histopathological evaluation show that the ATB+ST group did not present intestinal crypt distortion. Conclusion Cafeteria diet resulted in an expected weight gain. In relation to the ST, it has been shown that the procedure is effective in reducing weekly weight gain. Apparently, there was no induction of disabsortive syndrome in nonobese animals that received ST.

Resumo Introdução A obesidade é definida como uma síndrome metabólica multifatorial, na qual existe um número excessivo de células de gordura nos tecidos. Discute-se que a microbiota intestinal pode estar relacionada com a obesidade, uma vez que ela é alterada de forma relevante em pacientes obesos. Objetivos Avaliar o efeito do transplante de fezes (TF) na obesidade induzida por um modelo experimental de dieta de cafeteria. Métodos Quarenta ratos Wistar foram distribuídos aleatoriamente em 5 grupos: controle (CO), controle com antibióticos (CO+ATB), obesidade (CAF+ATB), transplante de fezes (ATB+TF) e obesidade com transplante de fezes (CAF+ATB+TF). Durante o experimento, os grupos de indução de obesidade receberam dieta de cafeteria, enquanto os demais grupos tiveram dieta ad libitum normal. Após 3 meses, o TF diário foi realizado por 8 semanas por meio de gavagem intragástrica. Os animais foram sacrificados e o intestino delgado foi colhido para análise posterior. Resultados Observou-se que antes de iniciar o TF, os grupos de dieta de cafeteria e dieta normocalórica apresentavam diferença significativa de peso (p<0,0001). Ao comparar os grupos CAF+ATB e CAF+ATB+TF durante o período de gavagem, o grupo CAF+ATB+TF apresentou menor ganho de peso (p=0,0017). A avaliação histopatológica mostra que nenhum dos animais do grupo TF+ATB apresentou distorções nas criptas intestinais. Conclusão A dieta da cafeteria resultou em um ganho de peso esperado. Em relação ao TF, demonstrou-se que o procedimento é eficaz na redução do ganho de peso semanal. Aparentemente, não houve indução da síndrome disabsortiva em animais não obesos que receberam TF.

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: una revisión / Fecal Microbial Transplantation: A Review

Resumen La microbiota intestinal sana se define a partir de la presencia de grupos de microorganismos que potencian el metabolismo del huésped. Estos microorganismos le confieren resistencia ante las infecciones, así como ante procesos inflamatorios y frente al desarrollo de neoplasias o autoinmunidad. Además, favorecen las funciones endocrinas y colaboran con la función neurológica a través del eje intestino-cerebro. Por otro lado, el trasplante de microbiota fecal consiste en la introducción de una suspensión de materia fecal de un donante sano en el tracto gastrointestinal de otra persona, que generalmente es un paciente que presenta una patología concreta. Esto se realiza con el fin de manipular la composición de la microbiota del destinatario y contribuir al tratamiento de su problema. El concepto de trasplante de microbiota fecal rompe con la consideración tradicional de las bacterias como elementos dañinos y presta atención a las que, probablemente, son las más subvaloradas de las excretas del cuerpo humano: las heces. En efecto, se ha evidenciado su alta eficacia y el procedimiento es reconocido por el número de pacientes a los que ha ayudado, que se puede ya cifrar en miles. El objetivo de esta revisión de literatura fue describir aspectos básicos para comprender el trasplante de microbiota fecal enfocado al tratamiento de infecciones producidas por Clostridioides difficile.

Abstract Gut microbiota is defined as healthy when there are groups of microorganisms that enhance the host's metabolism, confer resistance to infections, inflammatory processes, the development of malignancies or autoimmunity, promote endocrine functions and support neurological function through the so-called gut-brain axis. Fecal microbial transplantation is the transfer of fecal matter from a healthy donor into the gastrointestinal tract of another person, usually a patient with a specific pathology, to manipulate the composition of the recipient's microbiota and contribute to the treatment of his or her condition. The concept of fecal microbial transplantation breaks with the traditional thought of bacteria as harmful elements and draws attention to what is probably the most undervalued of the human body's excreta: feces. Its high efficiency has been demonstrated and the procedure is recognized by the many patients it has helped, which can already be counted in thousands. The objective of this literature review was to describe the basics of fecal microbial transplantation for the treatment of Clostridioides difficile infections.

Transplantes de microbiota fecal para tratamento da colite pseudomembranosa (1958-2013): prioridade de descoberta e estilos de pensamento na literatura acadêmica / Fecal microbiota transplants in the treatment of pseudomembranous colitis (1958-2013): priority of discovery and thought styles in the academic literature

Resumo Em 1958, Eiseman e colaboradores publicaram o primeiro artigo científico relatando o uso de transplante de microbiota fecal para tratar casos graves de colite pseudomembranosa. A relevância desse trabalho inovador só foi reconhecida em 1990. A literatura acadêmica sobre o tema caracteriza-se por sucessivas reconstruções. Sugerimos que tais reconstruções foram orientadas por questões de atribuição de prioridade de descoberta científica nos termos propostos por Merton. A retomada do uso de transplantes de microbiota fecal é interpretada como processo de gênese de um fato científico, conforme Fleck: ocorre a mudança de um estilo de pensamento baseado no uso de antibióticos no tratamento de doenças infecciosas para outro que considera as relações ecológicas entre hospedeiros, vetores e agentes etiológicos de doenças.

Abstract In 1958, Eiseman and contributors published the first scientific paper reporting the use of fecal microbiota transplant for treating pseudomembranous colitis. The relevance of this innovative paper was only acknowledged in 1990. The academic literature on the theme is characterized by a narrative that has undergone successive revisions. We suggest that such revisions were based on claims of priority of scientific discoveries, as described by Merton. The revival of fecal microbiota transplants is interpreted as a process of genesis of a scientific fact, as defined by Fleck: there is a switch from a thought style based on the use of antibiotics to treat infectious diseases to another that accepts the ecological relations between hosts, vectors and parasites.

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.

Efficacy of faecal microbiota transplantation for treating acute colitis in horses undergoing colic surgery / Eficácia do transplante de microbiota fecal no tratamento da colite aguda em equinos submetidos a cirurgia de cólica

The report describes the outcome of four horses treated with homologous faecal microbiota transplantation (FMT) for acute colitis. The horses developed diarrhoea and fever a few days after a laparotomy to treat gastrointestinal disease. Medical records were reviewed to identify the horses as well as to describe the primary intestinal disease, clinical findings, surgical intervention, FMT protocol, outcome and follow-up of each case. The principle of the efficacy of FMT is that restoration of a balanced nonpathogenic bacterial population may be the primary defence mechanism against colonization of pathogenic bacteria in the equine gastrointestinal tract. The FMT did not produce adverse reactions and was demonstrated to rapidly control diarrhoea and fever in all cases. A complete resolution of clinical sings was observed within 24 hours when horses were given a single FMT. Further clinical studies are necessary to determine the optimal preparation and to reinforce the efficacy of FMT for treating acute colitis following colic surgery. The technique has the potential to be an inexpensive, safe and highly efficient tool for the prevention and treatment of infectious gastrointestinal diseases in horses, preventing antimicrobial resistance.(AU)

O presente relato descreve a recuperação de 4 equinos tratados com transplante homólogo de microbiota fecal (TMF) para colite aguda. Os animais desenvolveram diarreia e febre alguns dias após serem submetidos a laparotomia para tratar obstruções intestinais. Os registros médicos foram revisados para identificar os equinos, bem como para descrever a doença intestinal primária, achados clínicos, detalhes da intervenção cirúrgica, protocolo do TMF, resultados e evolução de cada caso. O princípio da eficácia do TMF é que a restauração do equilíbrio de bactérias não patogênicas pode ser o principal mecanismo de defesa contra a colonização por bactérias patogênicas no trato gastrointestinal equino. O TMF não ocasionou reações adversas e demonstrou controlar rapidamente a diarreia e a febre em todos os casos. A resolução completa dos sinais clínicos foi observada dentro de 24 horas, sendo que os cavalos receberam um único TMF. Estudos clínicos adicionais são necessários para determinar a melhor técnica de preparação e para reforçar a eficácia do TMF no tratamento da colite aguda após cirurgia de cólica. A técnica tem potencial para ser uma ferramenta de baixo custo, segura e altamente eficiente para a prevenção e tratamento de doenças infecciosas gastrointestinais em equinos, evitando a resistência antimicrobiana.(AU)

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.

Manejo actualizado de la diarrea asociada a Clostridium difficile / Updated management of diarrhea associated with Clostridium difficile

The management of Clostridium difficile (CD) infection has changed in recent years. The latest clinical guidelines and systematic reviews suggest the use of vancomycin orally as the first line of treatment regardless the severity of the crisis (main difference compared to previous recommendations), this is due to changes in its epidemiology, the decrease in effectiveness and the increase of recurrences with the use of metronidazole, particularly in severe crisis. In addition, the use of new agents such as fidaxomicin has been approved. Fulminant crisis require an aggressive management combining oral treatment, enemas and intravenous therapy in addition to a collaborative management with the surgery team. With respect to recurrences, the use of vancomycin in pulses and with extended therapy schemes is suggested; fecal microbiota transplantation (FMT) is also an attractive therapy for patients with multiple recurrences. The following is a summary of the latest recommendations and available evidence regarding the management of CD infection in the most frequent situations, both in first crisis and in its recurrences.

El manejo de la infección por Clostridium difficile (CD) ha tenido modificaciones los últimos años. Las últimas guías clínicas y revisiones sistemáticas sugieren el uso de vancomicina vía oral como primera línea de tratamiento independiente de la severidad de la crisis (diferencia principal con recomendaciones previas), esto debido a cambios en su epidemiología, la disminución de la efectividad y al aumento de las recurrencias con el uso de metronidazol, particularmente en crisis severas. Además, han sido aprobados el uso de nuevos agentes como la fidaxomicina. Las crisis de carácter fulminante requieren un manejo agresivo combinando terapia oral, vía enemas e intravenosa, además de un manejo en conjunto con el equipo de cirugía. Respecto a las recurrencias se sugiere el uso de vancomicina en pulsos y con esquemas de terapia extendida siendo además, el trasplante de microbiota fecal (FMT) una terapia atractiva para pacientes con múltiples recurrencias. A continuación se resumen las últimas recomendaciones y evidencia disponible respecto del manejo de la infección por CD en las situaciones más frecuentes, tanto en la primera crisis como en sus recurrencias.

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.