Clostridioides difficile (C. difficile, previously known as Clostridium difficile) infections are a major health care concern. The Centers for Disease Control and Prevention (CDC) estimates that C. difficile causes almost half a million illnesses in the United States yearly, and approximately 1 in 5 patients with a C. difficile infection (CDI) will experience 1 or more recurrent infections. The incidence of infection has risen dramatically in recent years, and infection severity has increased due to the emergence of hypervirulent strains. There have been noteworthy advances in the development of CDI prevention and treatment, including a growth in the understanding of the role a patient's gut microbiome plays. The 2017 Infectious Diseases Society of America (IDSA) guidelines made a significant change in treatment recommendations for first time CDI episodes by recommending the use of oral vancomycin or fidaxomicin in place of metronidazole as a first-line treatment. The guidelines also included detailed recommendations on the use of fecal microbiota transplant (FMT) in those patients who experience 3 or more recurrent CDI episodes. A number of novel therapies for the treatment of CDI are in various stages of development. Treatments currently in phase 3 trials include the antibiotic ridinilazole, the microbiome products SER-109 and RBX2660, and a vaccine. All of these agents have shown promise in phase 1 and 2 trials. Additionally, several other antibiotic and microbiome candidates are currently in phase 1 or phase 2 trials. A qualitative review and evaluation of the literature on the cost-effectiveness of treatments for CDI in the U.S. setting was conducted, and the summary provided herein. Due to the higher cost of newer agents, cost-effectiveness evaluations will continue to be critical in clinical decision making for CDI. This paper reviews the updated CDI guidelines for prevention and treatment, the role of the microbiome in new and recurrent infections, pipeline medications, and comparative effectiveness research (CER) data on these treatments. DISCLOSURES: Durham and Le have nothing to disclose. Cassano reports consulting fees from Baxter Healthcare. Peer reviewers Drs. Ami Gopalan and Mark Rubin and Ms. Kathleen Jarvis have nothing to disclose. Planners Dr. Christine L. Cooper and Ms. Susan Yarbrough have nothing to disclose.
ANTECEDENTES: La infección por Clostridium difficile recurrente representa un reto clínico. El tratamiento se basa a menudo en la selección empírica de relativamente pocas opciones soportadas por la evidencia clínica limitada.
OBJETIVO: Revisar y evaluar la literatura sobre las alternativas terapéuticas para la infección por C. difficile recurrente.
FUENTES DE INFORMACIÓN: MEDLINE, PubMed, Embase y Cochrane bases de datos Se realizaron búsquedas desde su inicio hasta 2013 para la evidencia publicada en Inglés sobre el tratamiento de la infección por C. difficile recurrente. Los términos de búsqueda fueron "Clostridium difficile", "recurrente" o "recaída", y "tratamiento".
SELECCIÓN DE ESTUDIOS Y EXTRACCIÓN DE DATOS: Los estudios de cualquier diseño fueron elegibles para su inclusión. Dos revisores evaluaron los resúmenes, artículos completos, y listas de referencias de los artículos recuperados e guías de práctica clínica para identificar literatura relevante.
SÍNTESIS: La evidencia para orientar tratamiento de la infección por C. difficile recurrente se limita, con 24 estudios que cumplieran los criterios de inclusión para esta revisión. Se recomienda un curso de repetición de metronidazol oral o vancomicina para el tratamiento de leve a moderadas primera recurrencias y no se ha encontrado para influir en la probabilidad de recurrencia posterior. Vancomicina oral puede ser preferible para las infecciones más graves, sin embargo, las órdenes de puntuación de la gravedad de estudio y validación ulterior. Para el tratamiento de las recidivas segundo y siguientes, los regímenes de vancomicina cónicos o pulsantes se han recomendado en las guías de práctica, a pesar de la evidencia clínica muy limitada. Del mismo modo, los beneficios potenciales de cursos de tratamiento más largos de vancomicina oral para recurrencias segunda y posteriores garantizan la investigación. El papel potencial, incluyendo los costos de los beneficios y, de nuevos agentes tales como fidaxomicina en el tratamiento de la infección por C. difficile recurrente queda por determinar. Aunque no hay evidencia suficiente para recomendar probióticos como complemento al tratamiento convencional para la infección recurrente, puede haber beneficios en términos de prevención.
Conclusiones: Esta revisión de la literatura identificó limitaciones significativas en las intervenciones recomendadas actualmente para el tratamiento de la infección por C. difficile recurrente. También ha proporcionado información sobre la evidencia disponible para determinar la conveniencia de la terapia para los pacientes con infección recurrente.
Clostridioides difficile (C. difficile, previously known as Clostridium difficile) infections are a major health care concern. The Centers for Disease Control and Prevention (CDC) estimates that C. difficile causes almost half a million illnesses in the United States yearly, and approximately 1 in 5 patients with a C. difficile infection (CDI) will experience 1 or more recurrent infections. The incidence of infection has risen dramatically in recent years, and infection severity has increased due to the emergence of hypervirulent strains. There have been noteworthy advances in the development of CDI prevention and treatment, including a growth in the understanding of the role a patient's gut microbiome plays. The 2017 Infectious Diseases Society of America (IDSA) guidelines made a significant change in treatment recommendations for first time CDI episodes by recommending the use of oral vancomycin or fidaxomicin in place of metronidazole as a first-line treatment. The guidelines also included detailed recommendations on the use of fecal microbiota transplant (FMT) in those patients who experience 3 or more recurrent CDI episodes. A number of novel therapies for the treatment of CDI are in various stages of development. Treatments currently in phase 3 trials include the antibiotic ridinilazole, the microbiome products SER-109 and RBX2660, and a vaccine. All of these agents have shown promise in phase 1 and 2 trials. Additionally, several other antibiotic and microbiome candidates are currently in phase 1 or phase 2 trials. A qualitative review and evaluation of the literature on the cost-effectiveness of treatments for CDI in the U.S. setting was conducted, and the summary provided herein. Due to the higher cost of newer agents, cost-effectiveness evaluations will continue to be critical in clinical decision making for CDI. This paper reviews the updated CDI guidelines for prevention and treatment, the role of the microbiome in new and recurrent infections, pipeline medications, and comparative effectiveness research (CER) data on these treatments.
DISCLOSURES:
Durham and Le have nothing to disclose. Cassano reports consulting fees from Baxter Healthcare. Peer reviewers Drs. Ami Gopalan and Mark Rubin and Ms. Kathleen Jarvis have nothing to disclose. Planners Dr. Christine L. Cooper and Ms. Susan Yarbrough have nothing to disclose.
