Asunto(s)
Estreñimiento/complicaciones , Enterocolitis Seudomembranosa/tratamiento farmacológico , Enterocolitis Seudomembranosa/etiología , Adolescente , Enfermedad Crónica , Colon Descendente , Colon Sigmoide , Estreñimiento/tratamiento farmacológico , Estreñimiento/fisiopatología , Enterocolitis Seudomembranosa/fisiopatología , Femenino , Motilidad Gastrointestinal/fisiología , HumanosRESUMEN
The epidemiology of Clostridium difficile infections is highly dynamic as new strains continue to emerge worldwide. Here we present a detailed analysis of a new C. difficile strain (ICC-45) recovered from a cancer patient in Brazil that died from severe diarrhea. A polyphasic approach assigned a new PCR-ribotype and PFGE macrorestriction pattern to strain ICC-45, which is toxigenic (tcdA(+), tcdB(+) and ctdB(+)) and classified as ST41 from MLST Clade 2 and toxinotype IXb. Strain ICC-45 encodes for a variant TcdB that induces a distinct CPE in agreement with its toxinotype. Unlike epidemic NAP1/027 strains, which are also classified to MLST Clade 2, strain ICC-45 is susceptible to fluoroquinolones and does not overproduce toxins TcdA and TcdB. However, supernatants from strain ICC-45 and a NAP1/027 strain produced similar expression of pro-inflammatory cytokines, epithelial damage, and oxidative stress response in the mouse ileal loop model. These results highlight inflammation and oxidative stress as common features in the pathogenesis of C. difficile Clade 2 strains. Finally, this work contributes to the description of differences in virulence among various C. difficile strains.
Asunto(s)
Proteínas Bacterianas/genética , Toxinas Bacterianas/genética , Clostridioides difficile/aislamiento & purificación , Diarrea/diagnóstico , Enterocolitis Seudomembranosa/diagnóstico , Neoplasias/diagnóstico , Adulto , Animales , Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Toxinas Bacterianas/metabolismo , Clostridioides difficile/clasificación , Clostridioides difficile/efectos de los fármacos , Clostridioides difficile/genética , Diarrea/complicaciones , Diarrea/microbiología , Modelos Animales de Enfermedad , Enterocolitis Seudomembranosa/complicaciones , Enterocolitis Seudomembranosa/tratamiento farmacológico , Enterocolitis Seudomembranosa/microbiología , Femenino , Expresión Génica , Humanos , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Masculino , Ratones , Tipificación de Secuencias Multilocus , Neoplasias/complicaciones , Neoplasias/microbiología , Estrés Oxidativo , Filogenia , Reacción en Cadena de la Polimerasa , RibotipificaciónRESUMEN
In a 1-year survey at a university hospital we found that 20·6% (81/392) of patients with antibiotic associated diarrohea where positive for C. difficile. The most common PCR ribotypes were 012 (14·8%), 027 (12·3%), 046 (12·3%) and 014/020 (9·9). The incidence rate was 2·6 cases of C. difficile infection for every 1000 outpatients.
Asunto(s)
Clostridioides difficile/genética , Infección Hospitalaria/epidemiología , Enterocolitis Seudomembranosa/epidemiología , Hospitales Universitarios , Centros de Atención Terciaria , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Chile/epidemiología , Clostridioides difficile/efectos de los fármacos , Clostridioides difficile/aislamiento & purificación , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología , Enterocolitis Seudomembranosa/tratamiento farmacológico , Enterocolitis Seudomembranosa/microbiología , Humanos , Incidencia , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , RibotipificaciónRESUMEN
Clostridium difficile has become one of the main health care-associated infections. During the last decade increase in its incidence, recurrence, colectomy rate and mortality rate has made it necessary to establish the effectiveness of traditional therapies and has motivated the development of new therapies. New antibiotic treatments and alternative therapies have challenged management algorithms, especially in recurrent C. difficile infection. These include the fidaxomicin antibiotic which is selective against C. difficile and fecal microbiota transplantation. This review discussed therapies that are currently in use, their place in management algorithms and provides insight on developing therapies.
Clostridium difficile se ha convertido en una de las principales infecciones asociada a la atención de salud. El aumento en la última década de su incidencia, recurrencia, tasa de colectomía y mortalidad ha hecho necesario establecer la efectividad de las terapias tradicionalmente usadas y ha motivado el desarrollo de nuevas terapias. Nuevos tratamientos antibióticos, así como terapias alternativas a los antibióticos han desafiado los algoritmos de manejo, sobre todo en la infección por C. difficile recurrente. Entre éstos destacan el antibiótico fidaxomicina que es selectivo contra C. difficile y el trasplante de microbiota fecal. En esta revisión se analizan las terapias en uso actualmente, su lugar en los algoritmos de manejo y se dan luces sobre las terapias en desarrollo.
Asunto(s)
Humanos , Antibacterianos/uso terapéutico , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/cirugía , Trasplante de Microbiota Fecal , Aminoglicósidos/uso terapéutico , Clostridioides difficile , Enterocolitis Seudomembranosa/tratamiento farmacológico , Enterocolitis Seudomembranosa/cirugíaRESUMEN
BACKGROUND AND OBJECTIVE: Clostridium difficile NAP1/ribotype 027 is associated with severe disease and high mortality rates. Our aim was to determine the prevalence of NAP1/ribotype 027 among C. difficile isolates in a tertiary care hospital, and review the main clinical data. METHODS: We included 106 stool samples from 106 patients. Samples were tested for A&B toxins and were cultured on CCFA agar. The genes tcdA, tcdB, tcdC, cdtA, and cdtB were amplified using PCR in clinical isolates. The tcdA 3'-end deletion analysis, PCR-ribotyping, and pulsed-field gel electrophoresis (PFGE) were also performed. Stool samples that were positive for culture were tested by the GeneXpert C. difficile assay. Clinical data were collected. RESULTS: Thirty-six patients tested positive for A&B toxins; and 22 patients had positive culture for C. difficile, 14 of which tested positive for the A&B toxins and all 22 patients tested positive by the GeneXpert C. difficile assay. Risk factors included an average hospital stay of 16.1 days prior to toxin detection, average antibiotic use for 16.2 days, and a median of 3 antibiotics used. The 30-day crude mortality rate was 8.4%. Six of the 22 patients died, and 3 of those deaths were directly attributed to C. difficile infection. The majority of isolates, 90.9% (20/22), carried genes tcdB, tcdA, cdtA, and cdtB; and these strains carried the corresponding downregulator gene tcdC, with an 18-bp deletion. PFGE was performed on 17 isolates, and one main pattern was observed. Analysis of the ribotyping data showed similar results. CONCLUSION: The above findings represent the clonal spread of C. difficile in our institution, which mainly includes the NAP1/027 strain. This is the first report of C. difficile ribotype NAP1/027 in Mexico.
Asunto(s)
Proteínas Bacterianas/aislamiento & purificación , Toxinas Bacterianas/aislamiento & purificación , Clostridioides difficile/genética , Enterocolitis Seudomembranosa/epidemiología , Enterotoxinas/aislamiento & purificación , Genes Bacterianos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Clostridioides difficile/clasificación , Clostridioides difficile/aislamiento & purificación , Clostridioides difficile/patogenicidad , Electroforesis en Gel de Campo Pulsado , Enterocolitis Seudomembranosa/tratamiento farmacológico , Enterocolitis Seudomembranosa/microbiología , Enterocolitis Seudomembranosa/mortalidad , Heces/química , Heces/microbiología , Femenino , Humanos , Tiempo de Internación , Masculino , México/epidemiología , Persona de Mediana Edad , Ribotipificación , Factores de Riesgo , Análisis de Supervivencia , Centros de Atención TerciariaAsunto(s)
Antibacterianos/administración & dosificación , Clostridioides difficile , Enterocolitis Seudomembranosa , Heces , Trasplante de Células Madre Hematopoyéticas , Microbiota , Leucemia-Linfoma Linfoblástico de Células Precursoras , Vancomicina/administración & dosificación , Aloinjertos , Enterocolitis Seudomembranosa/tratamiento farmacológico , Enterocolitis Seudomembranosa/etiología , Femenino , Humanos , Metronidazol , Persona de Mediana EdadRESUMEN
BACKGROUND: Current Clostridium difficile infection (CDI) antibiotic regimens have become increasingly ineffective at achieving cure and preventing recurrence. A recently developed alternative to conventional antibiotics are phage tail-like particles (PTLPs), which are proteins that are morphologically similar to bacteriophages and are produced by C difficile. This study examines the in vitro killing spectrum of a previously unreported PTLP isolated from a clinical isolate of C difficile. METHODS: Using patient-derived samples from an institutional review board-approved C difficile tissue bank, a ribotype 078 C difficile isolate was anaerobically incubated on blood agar plates that were preswabbed with norfloxacin to induce the production of PTLPs. Concentrated PTLP populations were confirmed using transmission electron microscopy. Using a standard lawn spot approach, bactericidal activity was assessed as indicated by a clearing within the bacterial lawn. The PTLP genomic cluster was also fully sequenced and open reading frames were annotated according to predicted function. RESULTS: PTLPs were assessed using 64 patient-derived C difficile isolates of varying ribotypes. PTLPs demonstrated complete bactericidal activity in 21 of 25 ribotype 027 isolates with partial activity in 2 of the 25. Complete bactericidal activity was not demonstrated against any other ribotype or non-difficile bacteria, suggesting a species and ribotype specificity. Functional genes, which may be necessary for killing, were identified within the PTLP genetic locus. CONCLUSION: PTLPs demonstrate capability in eradicating C difficile in vitro, and with further development, may represent an organism-specific, microbiome-sparing therapy for CDI.
Asunto(s)
Proteínas Bacterianas/uso terapéutico , Clostridioides difficile/metabolismo , Enterocolitis Seudomembranosa/tratamiento farmacológico , Proteínas Bacterianas/metabolismo , Clostridioides difficile/genética , Humanos , Pruebas de Sensibilidad Microbiana , Ribotipificación , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Clostridium difficile-associated diarrhea (CDAD) has shown increasing incidence, morbidity, and mortality in recent years. We assessed the number of CDAD tests requested, CDAD positivity rates, the use of alcohol-based hand rubs, and antimicrobial utilization. METHODS: We collected information on every adult patient (>18 years) who developed diarrhea and had a positive stool test for C. difficile toxin from June 2005 to December 2009 at a tertiary care hospital. A time-series analysis was performed using monthly data on the incidence of C. difficile infection (CDI) (i.e., cases of infection per 1000 patient-days), as well as the consumption of alcohol-based hand rubs (in liters/1000-patient days) and antibiotics (in defined daily doses per 1000 patient-days). RESULTS: The mean number of annual requests for C. difficile tests was 1031, and the rates per 1000 patient-days for each year from 2005 to 2009 were 0.30, 0.46, 0.39, 0.31, and 0.40 overall in the hospital, and 0.18, 0.10, 0.53, 0.38, and 0.37 in the intensive care unit (ICU). The use of alcohol-based hand rubs per 1000 patient-days increased from 37.4 to 73.0, and from 41.5 to 129.4 in the hospital and in the ICU, respectively. CONCLUSIONS: The incidence of CDI in the hospital and ICU remained low, despite the increased use of alcohol-based hand rubs and antimicrobials.
Asunto(s)
Infección Hospitalaria , Diarrea/epidemiología , Enterocolitis Seudomembranosa/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Alcoholes , Antiinfecciosos/uso terapéutico , Clostridioides difficile/efectos de los fármacos , Diarrea/tratamiento farmacológico , Diarrea/prevención & control , Desinfectantes , Enterocolitis Seudomembranosa/tratamiento farmacológico , Enterocolitis Seudomembranosa/prevención & control , Femenino , Higiene de las Manos , Humanos , Incidencia , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The most frequent cause of pseudomembranous colitis is Clostridium difficile (C. difficile) infection. This type of colitis is characterized by an endoscopic pattern of numerous small, yellowish or whitish plaques diffusely distributed, which typically compromises the rectum extending to proximal colon. Occasionally, the pseudomembranes compromise only the transverse or right colon, but their exclusive localization over polyps has not been reported. In this case report we have described a patient with symptoms compatible with C. difficile infection and positive for C. difficile toxigenic culture. Colonoscopy examination showed two small polyps with a whitish surface, and histopathological analysis confirmed them to be pseudomembranes over tubular adenomas. The rest of the colonic mucosa was normal and no other cause was demonstrated. We suggest that this particular distribution might be due to a higher affinity for dysplastic cells such as adenomatous polyps of colon by C. difficile and/or its toxins.
Asunto(s)
Pólipos Adenomatosos/epidemiología , Clostridioides difficile , Neoplasias del Colon/epidemiología , Enterocolitis Seudomembranosa/epidemiología , Pólipos Adenomatosos/diagnóstico , Anciano de 80 o más Años , Antiinfecciosos/uso terapéutico , Neoplasias del Colon/diagnóstico , Colonoscopía , Comorbilidad , Enterocolitis Seudomembranosa/diagnóstico , Enterocolitis Seudomembranosa/tratamiento farmacológico , Femenino , Humanos , Metronidazol/uso terapéuticoRESUMEN
We report a 46 years old female subjected to a bilateral hip arthroplasty, who presented a diarrhea caused by Clostridium difficile. She was treated with metronidazole and vancomycin form 10 days with a good evolution. She was admitted again to the hospital three days later due to fever, malaise, diarrhea, abdominal distention and signs of hypotension. An abdominal CT scan showed images compatible with a pseudomembranous colitis. Due to the bad evolution, the patient was subjected to a total colectomy with a terminal ileostomy and closure of the rectal stump. During the postoperative period the patient was treated with parenteral nutrition, metronidazole and vancomycin. She was discharged 19 days after the operation. Fulminant colitis occurs in approximately 3 to 8 percent of patients with Clostridium difficile diarrhea and total colectomy is indicated when there is a poor response to medical treatment.
Se presenta el caso de una paciente de 46 años sometida a una artroplastía de cadera bilateral que presenta diarrea secundaria a infección por Clostridium difficile (CD), que fue tratada con metronidazol y vancomicina por 10 días con buena evolución. Reingresa 3 días después con un cuadro caracterizado por fiebre, compromiso del estado general, diarrea, distensión abdominal, deshidratación y signos de hipotensión. La tomografía computada (TC) mostró imágenes compatibles con colitis pseudomembranosa. Debido al deterioro hemodinámico a pesar del uso de drogas vasoactivas, se efectúa una colectomía total con ileostomía terminal y cierre del muñón rectal. Es apoyada con nutrición parenteral total, drogas vasoactivas y tratamiento antiobiótico específico con metronidazol y vancomicina. Luego de una tórpida evolución inicial, tiene buena evolución y se otorga el alta a los 19 días de la intervención. La Colitis Fulminante asociada a Clostridium difficile es una entidad grave que afecta al 3-8 por ciento de los casos con diarrea asociada a CD. La leucocitosis mayor de 16.000 /mm³, el uso de antibióticos en las últimas 8 semanas, la cirugía reciente (menos de 30 días) y el ácido láctico elevado eran los factores de riesgo presentes en esta paciente. La colectomía total abdominal sin anastomosis se justifica en los pacientes que no responden al tratamiento médico intensivo y/o con signos de peritonitis, 10 que ocurre aproximadamente en el 10-20 por ciento de los casos.
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Colectomía/métodos , Enterocolitis Seudomembranosa/cirugía , Enterocolitis Seudomembranosa/diagnóstico , Antiinfecciosos , Clostridioides difficile , Urgencias Médicas , Enterocolitis Seudomembranosa/tratamiento farmacológico , Metronidazol/uso terapéutico , Resultado del Tratamiento , Vancomicina/uso terapéuticoRESUMEN
OBJECTIVE: To review the management of patients with Clostridium difficile-associated diarrhoea (CDAD). METHODS: A retrospective study was conducted on 26 patients with clinical symptoms of CDAD and positive tests for C difficile toxins A and/or B in stool samples, over a 12- month period. Demographic and clinical data on the patients including use of proton pump inhibitors (PPI), management of CDAD, and compliance with local Infection Prevention and Control Guidelines were examined. RESULTS: The majority of patients were over 45 years of age (24/26, 92.4%) and 42% (11/26) were over 80 years of age. At least 50% (13/26) of the patients had acquired CDAD in hospital, 15% (4/26) were community acquired and symptomatic at admission while the onset of diarrhoea following admission to hospital was not documented in 35% (9/26). Three (11%) patients had used PPI. Fifteen per cent (4/26) of patients had no history of previous antibiotic therapy; 40% (10/26) were treated with a cephalosporin, fluoroquinolone or a combination of at least two different classes of antibiotics; one (3%) patient was on augmentin and the antibiotic regime used was not documented in 42% (11/26) who also had previous antibiotic therapy. The conditions for which antibiotics were prescribed could not be ascertained in 58% (15/26) but among the remaining cases antibiotics had been prescribed for urinary tract infection, wound respiratory tract infections and sepsis. Metronidazole (18/26, 70%) was the preferred drug of choice for first line therapy in patients with CDAD. None of the patients in the study received the recommended 10 to 14 days of antimicrobial therapy for CDAD. Recurrent CDAD was observed in 40% of those who were treated with metronidazole. The study also showed that there was timely reporting of laboratory results and good compliance with the hospital Infection Prevention and Control Guidelines. CONCLUSION: The findings of this study can be used as a process improvement measure in the management of patients with CDAD.
Asunto(s)
Antibacterianos/uso terapéutico , Clostridioides difficile , Infección Hospitalaria/prevención & control , Diarrea/tratamiento farmacológico , Diarrea/microbiología , Enterocolitis Seudomembranosa/tratamiento farmacológico , Enterocolitis Seudomembranosa/microbiología , Control de Infecciones/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Adhesión a Directriz , Hospitales Comunitarios , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVES: To review the management of patients with Clostridium difficile-associated diarrhoea (CDAD). METHODS: A retrospective study was conducted on 26 patients with clinical symptoms of CDAD and positive tests for C difficile toxins A and/or B in stool samples, over a 12- month period. Demographic and clinical data on the patients including use ofproton pump inhibitors (PPI), management of CDAD, and compliance with local Infection Prevention and Control Guidelines were examined. RESULTS: The majority ofpatients were over 45 years of age (24/26, 92.4%) and 42% (11/26) were over 80 years of age. At least 50% (13/26) of the patients had acquired CDAD in hospital, 15% (4/26) were community acquired and symptomatic at admission while the onset of diarrhoea following admission to hospital was not documented in 35% (9/26). Three (11%) patients had used PPI. Fifteen per cent (4/26) of patients had no history of previous antibiotic therapy; 40% (10/26) were treated with a cephalosporin, fluoroquinolone or a combination of at least two different classes of antibiotics; one (3%) patient was on augmentin and the antibiotic regime used was not documented in 42% (11/26) who also had previous antibiotic therapy. The conditions for which antibiotics were prescribed could not be ascertained in 58% (15/26) but among the remaining cases antibiotics had been prescribed for urinary tract infection, wound respiratory tract infections and sepsis. Metronidazole (18/26, 70%) was the preferred drug of choice for first line therapy in patients with CDAD. None of the patients in the study received the recommended 10 to 14 days of antimicrobial therapy for CDAD. Recurrent CDAD was observed in 40% of those who were treated with metronidazole. The study also showed that there was timely reporting oflaboratory results and good compliance with the hospital Infection Prevention and Control Guidelines. CONCLUSION: The findings of this study can be used as a process improvement measure in the management of patients with CDAD.
OBJETIVO: Revisar el tratamiento de pacientes con diarrea asociada con Clostridium difficile (DACD). MÉTODO: Se llevó a cabo un estudio retrospectivo de 26 pacientes aquejados por síntomas clínicos de DACD. Dichos pacientes resultaron positivos a pruebas de detección de toxinas A y/o B de C difficile en muestras de heces fecales por un período de 12 meses. Se examinaron los datos demográficos y clínicos de los pacientes, incluyendo el uso de inhibidores de la bomba de protones (IBP), tratamiento de la DACD, y el cumplimiento con las guías para el control de la infección local. RESULTADOS: La mayoría de los pacientes tenían más de 45 años de edad (24/26, 92.4%) y 42% (11/26) estaban por encima de los 80 años de edad. Al menos 50% (13/26) de los pacientes habían adquirido DACD en el hospital; el 15 % (4/26) la adquirió en la comunidad y presentaba síntomas al momento del ingreso; el comienzo de la diarrea tras el ingreso al hospital no se documentó en 35% (9/26) de los casos. Tres pacientes (11%) habían usado IBP. El 15% (4/26) de los pacientes no tenían antecedente alguno de terapia con antibióticos; un 40% (10/26) fue tratado con cefalosporina, fluoroquinolona, o una combinación por lo menos dos clases diferentes del antibióticos; un paciente (3%) se hallaba bajo tratamiento con augmentina y el régimen antibiótico usado no se documentó en el 42% (11/26) de los casos, que también tuvieron terapia antibiótica previa. No pudieron determinarse las condiciones para las que se prescribieron los antibióticos en el 58% (15/26), pero entre los casos restantes, se habían prescrito antibióticos para la infección de las vías urinarias, heridas, infecciones de las vías respiratorias, y sepsis. El metronidazol (18/26, 70%) fue el medicamento de opción preferida para la terapia de primera línea en los pacientes con DACD. Ninguno de los pacientes en el estudio recibió los 10 a 14 días de terapia antimicrobiana, recomendados para la DACD. Se observó DACD recurrente en 40% de aquéllos que fueron tratados con metronidazol. El estudio también mostró que hubo reportes oportunos de resultados de laboratorio y buen cumplimiento de las guías hospitalarias para el control de las infecciones. CONCLUSIÓN: Los hallazgos de este estudio pueden usarse como medida para mejorar el proceso encaminado a tratar a los pacientes con DACD.
Asunto(s)
Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Clostridioides difficile , Infección Hospitalaria/prevención & control , Diarrea/tratamiento farmacológico , Diarrea/microbiología , Enterocolitis Seudomembranosa/tratamiento farmacológico , Enterocolitis Seudomembranosa/microbiología , Control de Infecciones/métodos , Adhesión a Directriz , Hospitales Comunitarios , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Clostridium difficile (CD), es un bacilo gram positivo, anaerobio formador de esporas identificado como la principal causa de diarrea asociado al uso de antibióticos en pacientes hospitalizados. Los dos factores de riesgo más importantes para adquirir esta infección son el uso reciente de terapia antimicrobiana y la exposición al microorganismo productor de toxinas. La epidemiología de la enfermedad asociada a Clostridium difficile (EACD) ha cambiado sustancialmente en la última década, con un incremento sostenido en la incidencia y aparición de casos más severos, refractarios y recurrentes. La EACD abarca un amplio espectro de manifestaciones clínicas, que van de la portación asintomática, pasando por un cuadro de diarrea leve, hasta el desarrollo de colitis fulminante con una elevada tasa de mortalidad. El tratamiento antibiótico estándar es el metronidazol y vancomicina oral, con tasas de respuesta cercanas a un 95 por ciento por ; sin embargo, luego de la aparición de cepas hipervirulentas en el año 2003, la tasa de respuesta al metronidazol ha disminuido en forma significativa. Por ello, en los últimos años, se han comunicado una serie de estrategias y estudios con nuevos antimicrobianos con resultados alentadores. La terapia inmunológica pareciera tener un rol importante en la prevención de recurrencias así como en el manejo de pacientes con enfermedad severa. Se revisan aquellos aspectos más importantes relacionados con la infección asociada a CD.
Clostridium difficile (CD) is an anaerobic, gram-positive, spore-forming, toxin-producing bacillus. This is the leading cause of nosocomial diarrhea associated with antibiotic therapy in hospitalized patients. The two major risk factors for C. Difficile associated disease (CDAD) are recent exposure to an antibiotic and exposure to a toxin producing strain of the microorganism. Epidemiology of CDAD has changed substantially in the last decade, with an increase of incidence and occurrence of more severe, refractory and recurrent episodes. CDAD clinical spectrum varies from asymptomatic carriers, going from mild diarrhea to fulminant colitis with a high mortality rate. The standard antibiotic treatment is oral metronidazole and vancomycin, with response rates close to 90 percent, but after the appearance of hypervirulent strains in 2003, the response rate has decreased significantly. Therefore, in recent years many trials have reported a series of strategies and studies with new antimicrobial agents with promising results. Immunotherapy appears to play an important role in preventing recurrence and in the management of patients with a severe disease. The present article will review the most important aspects related to the infection associated with CD.
Asunto(s)
Humanos , Clostridioides difficile/patogenicidad , Diarrea/microbiología , Enterocolitis Seudomembranosa/microbiología , Enterocolitis Seudomembranosa/tratamiento farmacológico , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Diarrea/tratamiento farmacológico , Enterocolitis Seudomembranosa/epidemiología , Enterocolitis Seudomembranosa/inducido químicamente , Factores de Riesgo , Inmunoglobulinas/uso terapéutico , Metronidazol/uso terapéutico , Polímeros/uso terapéutico , Vancomicina/uso terapéutico , Índice de Severidad de la EnfermedadRESUMEN
Clostridium difficile associated disease (CDAD) has shown a sustained increase worldwide over the last ten years. However, there are few studies on this topic in Latin America. We conducted a comprehensive literature review using medical databases of Latin American countries. We found only seven recent papers in which clinical characteristics and risk factors were analyzed; some included outcome variables. Of these articles, only one was prospective, while the rest were either retrospective, cross-sectional or case-control studies. Most studies were done among hospitalized adult patients, even though patients 13+ years were also included in some reports. Only two recent clinical studies used cell culture to determine a cytopathic effect and the rest included immunoenzymatic assays. In general, all the studies we reviewed showed that the use of fluorquinolones, clindamycin, and cephalosporins were the antibiotics mostly associated with CDAD. Treatment schedules generally included metronidazol, although vancomycin was reported in one. Attributable mortality was lower than the mortality described in previous reports from hospitals in developed countries. Studies where this outcome was included did not surpass 4%, a significant difference from the findings from developed countries. In Latin America there are few studies that describe this clinical problem, they generally include small sample sizes and most are retrospective. There is a clear need to design and carry out prospective studies that will allow us to determine the true prevalence of this health problem
Asunto(s)
Enterocolitis Seudomembranosa , Enterocolitis Seudomembranosa/diagnóstico , Enterocolitis Seudomembranosa/tratamiento farmacológico , Humanos , América LatinaRESUMEN
La enfermedad asociada a Clostridium difficile (EACD) se ha incrementado de manera sostenida en todo el mundo durante los últimos 10 años. Sin embargo, son pocos los estudios en América Latina que abordan el tema. En una revisión bibliográfica en las bases de datos documentales de los países latinoamericanos, encontramos solo siete artículos recientes en los cuales se describen las características clínicas, los factores de riesgo y, en algunos, el desenlace de la infección. De estos artículos solo uno fue prospectivo, mientras que los restantes fueron retrospectivos, transversales o de casos y controles. Esta revisión estuvo orientada fundamentalmente hacia la población adulta en hospitalización, aunque la edad de los pacientes va de los 13 años en algunos trabajos. En dos análisis recientes se realizó cultivo celular para determinar efecto citopático y en el resto la determinación fue por inmunoensayo. En todos, el empleo de antibióticos (fluoroquinolonas, clindamicina y cefalosporinas) tuvo asociación con la EACD, y el tratamiento de la enfermedad incluyó casi siempre metronidazol por vía oral; únicamente en un centro se utilizó vancomicina. La mortalidad atribuible fue menor (4%) a la informada en países desarrollados. Dado que en América Latina existen escasas investigaciones de EACD con pocos pacientes y casi todas retrospectivas, se percibió la necesidad de determinar la frecuencia de esta enfermedad, conocer mejor los factores de riesgo y las verdaderas tasas de mortalidad global y atribuible.
Clostridium difficile associated disease (CDAD) has shown a sustained increase worldwide over the last ten years. However, there are few studies on this topic in Latin America. We conducted a comprehensive literature review using medical databases of Latin American countries. We found only seven recent papers in which clinical characteristics and risk factors were analyzed; some included outcome variables. Of these articles, only one was prospective, while the rest were either retrospective, cross-sectional or case-control studies. Most studies were done among hospitalized adult patients, even though patients 13+ years were also included in some reports. Only two recent clinical studies used cell culture to determine a cytopathic effect and the rest included immunoenzymatic assays. In general, all the studies we reviewed showed that the use of fluorquinolones, clindamycin, and cephalosporins were the antibiotics mostly associated with CDAD. Treatment schedules generally included metronidazol, although vancomycin was reported in one. Attributable mortality was lower than the mortality described in previous reports from hospitals in developed countries. Studies where this outcome was included did not surpass 4%, a significant difference from the findings from developed countries. In Latin America there are few studies that describe this clinical problem, they generally include small sample sizes and most are retrospective. There is a clear need to design and carry out prospective studies that will allow us to determine the true prevalence of this health problem
Asunto(s)
Humanos , Enterocolitis Seudomembranosa , Enterocolitis Seudomembranosa/diagnóstico , Enterocolitis Seudomembranosa/tratamiento farmacológico , América LatinaRESUMEN
Clostridium difficile-associated diarrhea usually occurs as a complication of antibiotic treatment. Recent data shows an increase in incidence rate of CDAD and higher rates of morbidity, colectomy and death. The management of CDAD involves discontinuing the inciting antibiotic agent and treatment with metronidazole or vancomycin. The reduced response rates and higher recurrence rates with metronidazole treatment reported in recent studies raise the question of the effectiveness of metronidazole therapy. After each recurrence, the risks for further relapses grow even bigger (after two recurrences, the risk being greater than 50%) and the management of recurrent CDAD becomes a challenge. Even after a careful review of available data on various drugs and having the experience of managing many cases of CDAD, one might find difficult to present with a successful "recipe" for treating severe CDAD. Every case is different and different management plans can lead to full recovery. First episode are metronidazole. If there is no improvement in three days or white blood cell count is more than 12,000 or creatinine level is high, metronidazole should be discontinued and vancomycin should be started. The latest trend of CDAD with more severe cases and increasing morbidity and mortality may be an incentive for using vancomycin as first line in some ases for RCDAD. Adding S boulardii to vancomycin or metronidazole from the first or second relapse and using pulse/tapering vancomycin therapy have been beneficial in decreasing the relapse rate. For patients with RCDAD, vancomycin therapy followed by rifaximin for two weeks looks promising. New therapies with, nitazoxanide, tinidazole, tiacumicin, rifaximin and ramoplanin are being evaluated and future reports and trials will show their efficacy. Immune therapy is also a promising option treatment in evaluation, showing seroconversion and protective antibody levels in initial tests in healthy volunteer. Passive immunization is also considered but for all these new therapy options, further randomized studies are needed. Prevention is also very important in controlling this disease: first by limiting the use of broad spectrum antibiotics and secondly by controlling the environmental spreading through gloves, handwashing and disposable thermometers.
Asunto(s)
Clostridioides difficile , Diarrea/microbiología , Enterocolitis Seudomembranosa/tratamiento farmacológico , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Diarrea/tratamiento farmacológico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Probióticos/uso terapéutico , RecurrenciaRESUMEN
BACKGROUND: Clostridium difficile-associated disease (CDAD) is a serious nosocomial infection, however few studies have assessed CDAD outcome in the intensive care unit (ICU). We evaluated the epidemiology, clinical course and outcome of hospital-acquired CDAD in the critical care setting. METHODS: We performed a historical cohort study on 58 adults with a positive C. difficile cytotoxin assay result occurring in intensive care units. RESULTS: Sixty-two percent of patients had concurrent infections, 50% of which were bloodstream infections. The most frequently prescribed antimicrobials prior to CDAD were anti-anaerobic agents (60.3%). Septic shock occurred in 32.8% of CDAD patients. The in-hospital mortality was 27.6%. Univariate analysis revealed that SOFA score, at least one organ failure and age were predictors of mortality. Charlson score >/=3, gender, concurrent infection, and number of days with diarrhea before a positive C. difficile toxin assay were not significant predictors of mortality on univariate analysis. Independent predictors for death were SOFA score at infection onset (per 1-point increment, OR 1.40; CI95 1.13-1.75) and age (per 1-year increment, OR 1.10; CI95 1.02-1.19). CONCLUSION: In ICU patients with CDAD, advanced age and increased severity of illness at the onset of infection, as measured by the SOFA score, are independent predictors of death.