We recently compared results of fecal microbiota transplantation (FMT) in patients with refractory, recurrent Clostridium difficile infection (rCDI), with and without underlying inflammatory bowel disease (IBD). Here we extend this cohort and analyze outcomes in greater detail by subtype of IBD. We find that FMT is generally effective in breaking the cycle of CDI recurrence, but its effects on overall IBD progression are much less predictable. We discuss several challenges intrinsic to this complex clinical situation and outline the next steps that can address these challenges going forward.
Gut microbiota play a key role in maintaining homeostasis in the human gut. Alterations in the gut microbial ecosystem predispose to Clostridium difficile infection (CDI) and gut inflammatory disorders such as inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) from a healthy donor can restore gut microbial diversity and pathogen colonization resistance; consequently, it is now being investigated for its ability to improve inflammatory gut conditions such as IBD. In this study, we investigated changes in gut microbiota following FMT in 38 patients with CDI with or without underlying IBD.
BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) has recently been shown to be a promising therapy for recurrent and refractory Clostridium difficile infections (CDI) despite lack of protocol standardization. Patients with inflammatory bowel disease (IBD) present a particular challenge to CDI therapy as they are reported to have worse clinical outcomes, including higher colectomy rates and increased mortality. We aimed to assess the outcomes of FMT for recurrent CDI in patients with IBD at our healthcare system.
METHODS: We constructed a retrospective cohort of all patients who underwent FMT at our healthcare system between December 2012 and May 2014. Patients with concurrent IBD were identified. We evaluated the differences in demographic and clinical characteristics, along with the outcomes to FMT between patients with IBD as compared to the general population.
RESULTS: Over the study period, 201 patients underwent FMT of which 20 patients had concurrent IBD. Patients with IBD were younger but did not differ from the general population in terms of CDI risk factors or disease severity. The response to FMT and rate of CDI relapse in the IBD group were not statistically different compared to the rest of the cohort. The overall response rate in the IBD population was 75% at 12 weeks. Of the patients who failed FMT 4 of 5 patients had active or untreated IBD.
CONCLUSION: Fecal microbiota transplantation provides a good alternative treatment option with high success rates for recurrent or refractory Clostridium difficile infection in patients with well-controlled IBD who fail standard antimicrobial therapy.
BACKGROUND & AIMS: A significant fraction of patients with recurrent Clostridium difficile infections (CDI) have inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) can break the cycle of CDI recurrence and can be performed without evaluation of the colon. We evaluated the efficacy of colonoscopic FMT in patients with and without IBD, and whether we could identify IBD in patients during this procedure.
METHODS: We collected clinical meta-data and colonoscopy results from 272 consecutive patients that underwent FMT for recurrent CDI at the University of Minnesota from 2008 through 2015. Patients had at least 2 spontaneous relapses of CDI following their initial episode and did not clear the infection after 1 extended antibiotic regimen. We collected random mucosal biopsies from patients' right colons to identify lymphocytic or collagenous colitis during the FMT procedure. Failure or success in clearing CDI was determined within or at 2 months after the FMT.
RESULTS: Of patients undergoing FMT, 15% had established IBD and 2.6% were found to have IBD during the FMT procedure. A single colonoscopic FMT cleared CDI from 74.4% of patients with IBD and 92.1% of patients without IBD (P = .0018). Patients had similar responses to FMT regardless of immunosuppressive therapy. More than one-quarter of patients with IBD (25.6%) had a clinically significant flare of IBD after FMT. Lymphocytic colitis was documented in 7.4% of patients with endoscopically normal colon mucosa; only 3 of these patients (20%) required additional treatment for colitis after clearance of CDI.
CONCLUSIONS: Based on an analysis of 272 patients, FMT is somewhat less effective in clearing recurrent CDI from patients with IBD, compared with patients without IBD, regardless of immunosuppressive therapy. More than 25% of patients with IBD have a disease flare following FMT. Lymphocytic colitis did not affect the outcome of FMT, but a small fraction of these patients required pharmacologic treatment after the procedure.
OBJECTIVES: Fecal microbiota transplant (FMT) is a highly efficacious treatment for recurrent or refractory Clostridium difficile infection (CDI); however, 10-20% of patients fail to achieve cure after a single FMT. The aim of this study was to identify risk factors associated with FMT failure and to develop and validate a prediction model for FMT failure.
METHODS: Patient characteristics, CDI history, FMT characteristics, and outcomes data for patients treated between 2011 and 2015 at three academic tertiary referral centers were prospectively collected. Early FMT failure was defined as non-response or recurrence of diarrhea associated with positive stool C. difficile toxin or PCR within 1 month of FMT. Late FMT failure was defined as recurrence of diarrhea associated with positive stool C. difficile toxin or PCR between 1 and 3 months of the FMT. Patient data from two centers were used to determine independent predictors of FMT failure and to build a prediction model. A risk index was constructed based on coefficients of final predictors. The patient cohort from the third center was used to validate the prediction model.
RESULTS: Of 328 patients in the developmental cohort, 73.5% (N=241) were females with a mean age of 61.4±19.3 years; 19.2% (N=63) had inflammatory bowel disease (IBD), and 23.5% (N=77) were immunocompromised. The indication for FMT was recurrent CDI in 87.2% (N=286) and severe or severe-complicated in 12.8% (N=42). FMT was performed as an inpatient in 16.7% (N=54). The stool source was patient-directed donors in 40% (N=130) of cases. The early FMT failure rate was 18.6%, and the late failure rate was 2.7%. In the multivariable analysis, predictors of early FMT failure included severe or severe-complicated CDI (odds ratio (OR) 5.95, 95% confidence interval (CI): 2.26-15.62), inpatient status during FMT (OR 3.78, 95% CI: 1.55-9.24), and previous CDI-related hospitalization (OR 1.43, 95% CI: 1.18-1.75); with each additional hospitalization, the odds of failure increased by 43%. Risk scores ranged from 0 to 13, with 0 indicating low risk, 1-2 indicating moderate risk, and ≥3 indicating high risk. In the developmental cohort, early FMT failure rates were 5.6% for low risk, 12.7% for moderate risk, and 41% for high-risk patients. Of 134 patients in the validation cohort, 57% (N=77) were females with a mean age of 66±18.1 years; 9.7% (N=13) had IBD, and 17.9% (N=24) were immunocompromised. The early FMT failure rate at 1 month was 19.4%, with an additional 3% failing by 3 months. In the validation cohort, FMT failure rates were 2.1% for low risk, 16.1% for moderate risk, and 35.7% for high risk patients. The area under the receiver operating characteristic curve (AUROC) for FMT failure was 0.81 in the developmental cohort and 0.84 in the validation cohort.
CONCLUSIONS: Severe and severe-complicated indication, inpatient status during FMT, and the number of previous CDI-related hospitalizations are strongly associated with early failure of a single FMT for CDI. The novel prediction model has good discriminative power at identifying individuals who are at high risk of failure after FMT therapy and may assist the treating physician in subsequent management plans.
BACKGROUND: New treatments are needed as Clostridium difficile infection (CDI) is becoming increasingly formidable. Fecal microbiota transplantation (FMT) has a 90% success rate in the treatment of recurrent CDI. However, evidence regarding its safety, efficacy, and effect on disease activity in patients with inflammatory bowel disease (IBD) is lacking.
METHODS: This cohort study used data from 8 national and international academic centers. Patients with established IBD who underwent FMT for recurrent CDI were followed for a minimum of 3 months. The primary outcome was CDI recurrence at 3 months after FMT. The secondary outcomes were (1) IBD activity and severity at 3 months based on the judgment of the treating physician, endoscopic findings, and clinical disease activity scores; and (2) safety.
RESULTS: Sixty-seven patients were included in the analysis. Thirty-five (52%) had Crohn's disease, 31 (46%) ulcerative colitis, and one indeterminate colitis with 43 (64%) patients on an immunosuppressive agent at the time of FMT. The initial FMT was successful in 53 (79%) patients. After the FMT, IBD disease activity was reported as improved in 25 (37%), no change in 20 (30%), and worse in 9 (13%) patients. Serious adverse events included colectomy (1.4%), hospitalization for CDI (2.9%), hospitalization for IBD flare (2.9%), small bowel obstruction (1.4%), CMV colitis (1.4%), and pancreatitis (1.4%).
DISCUSSION: The overall CDI cure rates were high, with a large percentage of patients experiencing clinical improvement of their IBD after FMT. A minority of patients developed an IBD flare. No severe adverse events directly attributable to FMT were found in this largest reported series of recurrent or refractory CDI patients with concurrent IBD.
OBJETIVOS: Los pacientes que tienen el sistema inmunitario (IC) tienen un mayor riesgo de infección por Clostridium difficile (CDI), que ha aumentado en proporciones epidémicas en la última década. El trasplante fecal microbiota (FMT) parece ser eficaz para el tratamiento de la CDI, aunque existe la preocupación de que los pacientes con CI pueden estar en mayor riesgo de sufrir acontecimientos adversos (AA) relacionados con la FMT. Este estudio describe la experiencia multicéntrica de FMT en pacientes con CI.
MÉTODOS: Una serie retrospectiva multicéntrico, realizado en el uso de FMT en pacientes con CI con CDI que era recurrente, refractario, o grave. El objetivo fue describir las tasas de curación después de la FMT CDI, así como acontecimientos adversos experimentados por los pacientes con CI después de la FMT. Un cuestionario de 32 ítems para recoger datos demográficos y pre-y post-FMT fue completado por 99 pacientes en 16 centros, de los cuales 80 fueron elegibles para su inclusión. Los resultados incluyeron (i) tasas de curación CDI después de la FMT, (ii) los eventos adversos graves (AAG) como la muerte o la hospitalización dentro de las 12 semanas de FMT, (iii) la infección dentro de las 12 semanas de FMT, y (iv) las reacciones adversas (relacionadas entre sí y no relacionado) a FMT.
Resultados: Los casos incluidos adulto (75) y pediátrica (5) pacientes tratados con FMT para recurrente (55%), refractaria (11%), y la severa y / o superposición de recurrente / refractaria y severa CDI (34%). En total, el 79% eran pacientes ambulatorios en el momento de FMT. El período de seguimiento medio entre FMT y la recogida de datos fue de 11 meses (rango 3-46 meses). Las razones de IC incluyen: el VIH / SIDA (3), el trasplante de órganos sólidos (19), condición oncológica (7), la terapia inmunosupresora para la enfermedad inflamatoria intestinal (EII; 36), y otras condiciones médicas / medicamentos (15). La tasa de curación después de una sola CDI FMT fue del 78%, con 62 pacientes que sufren ninguna recurrencia al menos 12 semanas después de la FMT. Doce pacientes fueron sometidos a repetir FMT, de los cuales ocho tenían ninguna otra CDI. Por lo tanto, la tasa de curación global fue del 89%. Doce (15%) tenían ninguna SAE dentro de las 12 semanas después de la FMT, de los cuales 10 fueron hospitalizaciones. Dos muertes ocurrieron dentro de las 12 semanas de FMT, uno de los cuales era el resultado de la aspiración durante la sedación para FMT administrado a través de la colonoscopia; el otro era ajeno a FMT. Ninguno sufrido infecciones duda relacionada con la FMT, pero dos pacientes desarrollaron infecciones no relacionadas y cinco tenían enfermedad diarreica autolimitada en el que no se identificó ningún organismo causal. Un paciente tuvo un desgarro de la mucosa superficial causada por la colonoscopia realizada por la FMT, y tres pacientes informó, autolimitada malestar abdominal posterior FMT leve. Cinco (14% de los pacientes con EII) experimentaron enfermedad llamarada mensaje FMT. Tres colitis ulcerosa (CU) pacientes fueron sometidos a colectomía relacionado con el programa de la Universidad de California> 100 días después de la FMT.
CONCLUSIONES: Esta serie demuestra el uso efectivo de FMT de CDI en pacientes con CI con pocos eventos adversos graves relacionados o AES. Es importante destacar que no hubo complicaciones infecciosas relacionadas en estos pacientes de alto riesgo.
OBJETIVOS: Aunque el trasplante de microbiota fecal (FMT) se conoce históricamente como un medio eficaz para el tratamiento de la infección por Clostridium difficile recurrente (CDI) refractarios a los tratamientos antibióticos convencionales, rara vez se realiza el procedimiento. Al menos algunas de las razones de disponibilidad limitada son aquellos de la practicidad, incluyendo las preocupaciones estéticas y los costos de selección de donantes. El objetivo de este estudio fue el de superar estas barreras en nuestro programa FMT clínica.
MÉTODOS: Se presenta la experiencia clínica con 43 pacientes consecutivos que fueron tratados con FMT para CDI recurrente desde el inicio de este programa en la Universidad de Minnesota. Durante este tiempo, hemos simplificado la identificación del donante y la detección de movimiento de donantes individuales del paciente identificado a los donantes voluntarios habituales. Preparación del material desplazado de la sala de endoscopia a un proceso estandarizado en el laboratorio, y en última instancia a la banca materia fecal procesada congelada que está listo para usar cuando sea necesario.
RESULTADOS: Normalización de la preparación de material de simplificar significativamente los aspectos prácticos de la FMT y sin pérdida de la aparente eficacia en la limpieza de CDI recurrente. Aproximadamente el 30% de los pacientes tenían antecedentes de enfermedad inflamatoria del intestino, y FMT fue igualmente eficaz en este grupo.
Conclusiones: Varios pasos clave en la normalización de la preparación del material donante simplifican significativamente la práctica clínica de la FMT para CDI recurrente en pacientes que no la terapia con antibióticos.
We recently compared results of fecal microbiota transplantation (FMT) in patients with refractory, recurrent Clostridium difficile infection (rCDI), with and without underlying inflammatory bowel disease (IBD). Here we extend this cohort and analyze outcomes in greater detail by subtype of IBD. We find that FMT is generally effective in breaking the cycle of CDI recurrence, but its effects on overall IBD progression are much less predictable. We discuss several challenges intrinsic to this complex clinical situation and outline the next steps that can address these challenges going forward.
