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Abstract Clostridium difficile infection (CDI) is the most common hospital acquired diarrheal disease with its increasing incidence and mortality rate globally. DNA Gyrase B (GyrB) is a key component of DNA replication process across all bacterial genera; thus, this offers a potential target for the treatment of CDI. In the present study, several virtual screening approaches were employed to identify a novel C. difficile GyrB inhibitor. The 139 known metabolites were screened out from the 480 flavonoids in PhytoHub database. Molinspiration and PROTOX II servers were used to calculate the ADME properties and oral toxicity of the metabolites, whereas mutagenicity, tumorigenicity, irritant, and reproductive effect were predicted using DataWarrior program. The binding mode and the binding efficiency of the screened flavonoids against the GyrB were studied using FlexX docking program. From virtual screening of 139 metabolites, we found 25 flavonoids with no mutagenicity, tumorigenicity, irritant, and reproductive effect. Docking study suggested that flavonoids 1030 ((-)-epicatechin 3'-O-sulfate), 1032 ((-)-epicatechin 4'-O-sulfate), 1049 (3'-O-methyl-(-)-epicatechin 4-O-sulfate), 1051 (3'-O-methyl-(-)-epicatechin 7-O-sulfate), 1055 (4'-O-methyl-(-)-epicatechin 7-O-sulfate) and 1317 (quercetin sulfate) have significantly higher binding affinity than the known GyrB inhibitor novobiocin. The results from molecular dynamics simulation and free energy calculations based on solvated interaction energy suggested that (-)-epicatechin 3'-O-sulfate could be a potential drug candidate in the management of CDI.
Assuntos
Flavonoides/uso terapêutico , Infecções por Clostridium/terapia , DNA Girase/uso terapêutico , Ensaios de Triagem em Larga EscalaRESUMO
Introdução: 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 um 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, foram relatados poucos casos isolados de TMF, com taxa de sucesso em torno de 90%, realizados de forma experimental, sem a implantação de um Centro de Transplante de Microbiota Fecal (CTMF). É objetivo principal desse estudo descrever o processo envolvido na implantação de um Centro de Transplante de Microbiota Fecal (CTMF) no Instituto Alfa de Gastroenterologia do Hospital das Clínicas da UFMG/EBSERH (IAG-HC/UFMG) para o tratamento de infecção recorrente e refratária pelo C. difficile e analisar prospectivamente os resultados do tratamento a curto e longo prazo. Métodos: O CTMF foi estruturado dentro dos critérios exigidos e aprovados por organismos internacionais como o FDA (Food and Drug Administration), Grupo Europeu de Transplante de Microbiota Fecal e em consonância com os aspectos epidemiológicos e regulatórios nacionais. Resultados: Foi estabelecida plataforma que define todas as etapas envolvidas na seleção de doadores universais, processamento e armazenamento de amostras, uniformização de vias de administração do substrato fecal e seguimento a curto e longo prazo dos pacientes transplantados. A seleção de doadores foi realizada em três etapas: pré-triagem, avaliação clínica e triagem laboratorial. A maioria dos candidatos foi excluída na primeira (75,4%) e segunda etapa (72,7%). Os principais critérios clínicos de exclusão foram: diarreia aguda recente, excesso de peso (índice de massa corporal ≥ 25 kg / m²) e distúrbios gastrointestinais crônicos. Apenas quatro dos 134 candidatos foram selecionados como doadores após rastreio completo, com taxa de detecção de doadores habilitados de 3%. Ao todo foram realizados 11 transplantes em 10 pacientes com ICD recorrente. A taxa de resolução primária, com apenas um procedimento, foi de 80% e a taxa de remissão geral, após segundo TFM, foi de 90%. A ocorrência de eventos adversos foi semelhante à observada em outros estudos. A maioria dos eventos adversos foram autolimitados e de resolução espontânea. Conclusão: A implantação de um centro de transplante, inédito no nosso país, permitiu o acesso de pacientes com infecção recorrente pelo C. difficile a tratamento inovador, seguro e efetivo. A seleção adequada de doadores qualificados é vital no processo de implantação de um CTMF. A rigorosa avaliação clínica dos doadores permitiu o uso racional de recursos. Um centro de transplante de microbiota possibilita oferecer um tratamento sob demanda, menos personalizado, com mais segurança e rastreabilidade. Mesmo em países emergentes, onde há preocupação com doenças tropicais e infecciosas, o TMF parece ser uma estratégia segura e efetiva no tratamento de ICD recorrente.
Assuntos
Clostridioides difficile , Transplante de Microbiota Fecal , Hospitais , Dissertação Acadêmica , FezesRESUMO
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)
Assuntos
Humanos , Masculino , Feminino , Infecções por Clostridium/terapia , Transplante de Microbiota Fecal/métodos , Infecções por Clostridium/epidemiologiaRESUMO
INTRODUCTION: The prevalence of Clostridium difficile infection is rapidly increasing worldwide, but prevalence is difficult to estimate in developing countries where awareness, diagnostic resources, and surveillance protocols are limited. As diarrhea is the hallmark symptom, we conducted a systematic review and meta-analysis to determine the prevalence and incidence of C. difficile infection in patients in these regions who presented with diarrhea. METHODS: We conducted a systematic literature search of MEDLINE/PubMed, Scopus, and Latin-American and Caribbean Health Sciences Literature databases to identify and analyze data from recent studies providing prevalence or incidence rates of C. difficile-associated diarrhea in developing countries within four regions: Africa-Middle East, developing Asia, Latin America, and China. Our objectives were to determine the current prevalence and incidence density rates of first episodes of C. difficile-associated diarrhea in developing countries. RESULTS: Within the regions included in our analysis, prevalence of C. difficile infection in patients with diarrhea was 15% (95% CI 13-17%) (including community and hospitalized patients), with no significant difference across regions. The incidence of C. difficile infection in 17 studies including this information was 8.5 per 10,000 patient-days (95% CI 5.83-12.46). Prevalence was significantly higher in hospitalized patients versus community patients (p = 0.0227). CONCLUSION: Our prevalence estimate of 15% is concerning; however, low awareness and inconsistent diagnostic and surveillance protocols suggest this is markedly underestimated. Enhanced awareness and management of C. difficile infection in patients with diarrhea, along with improvements in infection control and surveillance practices, should be implemented to reduce prevalence of C. difficile-associated diarrhea in developing countries. FUNDING: Pfizer Inc.
RESUMO
The best laboratory diagnostic approach to detect Clostridioides [Clostridium] difficile infection (CDI) is a subject of ongoing debate. With the aim of evaluating four laboratory diagnostic methods, 250 unformed stools from patients with suspected CDI submitted to nine medical center laboratories from November 2010 to December 2011, were studied using: (1) an immunochromatographic rapid assay test that combines the qualitative determination of glutamate dehydrogenase (GDH) plus toxins A and B (QAB), the CDIFF QUIK CHEK COMPLETE assay; (2) an enzyme immunoassay for qualitative determination of toxins A and B, the RIDASCREEN™ C. difficile Toxin A/B assay (RAB); (3) a PCR for the toxin B gene assay (PCR); and (4) the toxigenic culture (TC). C. difficile isolates from direct toxin negative stools by QAB, RAB and PCR were evaluated for toxigenicity by the same direct tests, in order to assess the contribution of the TC (QAB-TC, RAB-TC, PCR-TC). A combination of the cell culture cytotoxicity neutralization assay (CCCNA) in stools, and the same assay on isolates from direct negative samples (CCCNA-TC) was considered the reference method (CCCNA/CCCNA-TC). Of the 250 stools tested, 107 (42.8%) were positive by CCCNA/CCCNA-TC. The GDH and PCR/PCR-TC assays were the most sensitive, 91.59% and 87.62%, respectively. The QAB, RAB, QAB/QAB-TC and RAB/RAB-TC had the highest specificities, ca. 95%. A negative GDH result would rule out CDI, however, its low positive likelihood ratio (PLR) of 3.97 indicates that a positive result should always be complemented with the detection of toxins. If the RAB, QAB, and PCR assays do not detect toxins from direct feces, the toxigenic culture should be performed. In view of our results, the most accurate and reliable methods to be applied in a clinical microbiology laboratory were the QAB/QAB-TC, and RAB/RAB-TC, with PLRs >10 and negative likelihood ratios <0.30.
Assuntos
Toxinas Bacterianas , Clostridioides difficile , Técnicas Imunoenzimáticas , Reação em Cadeia da Polimerase , Proteínas de Bactérias , Toxinas Bacterianas/análise , Clostridioides difficile/genética , Enterotoxinas , Fezes , Humanos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND AND AIM: Clostridium difficile is a major cause of health care-associated infection, but disagreement between diagnostic tests is an ongoing barrier to clinical decision-making. Conventional enzyme immunoassay (EIA) for toxin detection is currently the most frequently used technique for C. difficile infection (CDI) diagnosis, but its low sensitivity makes the development of an alternative strategy necessary for improving the diagnosis in developing countries. METHODS: Between years 2011 and 2015, 154 stool samples from patients with antibiotic-associated diarrhea were examined by toxigenic culture and EIA for the diagnosis of CDI. In the year 2015, when glutamate dehydrogenase (GDH) test was first available in Brazil, 53 of those fecal specimens were also tested by the C. diff Quik Chek Complete rapid immunoassay. At this time, we prospectively assessed the impact of this test on CDI treatment rates before and after it was introduced in clinical practice. RESULTS: The GDH component of C. diff Quik Chek Complete test had a sensitivity of 100% and specificity of 95.1% compared with toxigenic culture, with 89.8% concordance. The Tox A/B II EIA and the toxin portion of C. diff Quik Chek Complete yielded sensitivities between values of 50-58.3%, with 100% specificities. The introduction of GDH test increased the number of treated patients with CDI from 57.7% to 100%. CONCLUSIONS: Glutamate dehydrogenase test is a reliable method for the diagnosis of CDI and greatly increases the number of properly treated patients with CDI. Therefore, this exam should be considered the mainstay for the laboratory diagnosis of CDI in developing countries.
Assuntos
Antibacterianos/efeitos adversos , Proteínas de Bactérias/análise , Toxinas Bacterianas/análise , Clostridioides difficile/patogenicidade , Infecções por Clostridium/diagnóstico , Diarreia/etiologia , Diarreia/microbiologia , Enterotoxinas/análise , Glutamato Desidrogenase/análise , Técnicas Imunoenzimáticas/métodos , Corantes Azur , Biomarcadores/análise , Brasil , Clostridioides difficile/enzimologia , Clostridioides difficile/metabolismo , Infecções por Clostridium/microbiologia , Fezes/microbiologia , Hospitais Universitários , Humanos , Azul de Metileno , Estudos Prospectivos , Sensibilidade e Especificidade , XantenosRESUMO
Resumen:La infección por Clostridium difficile es la principal causa de diarrea infecciosa en pacientes hospitalizados. Los pacientes pueden ser portadores asintomáticos o presentar desde una diarrea leve a una colitis pseudomembranosa, megacolon tóxico, sepsis y muerte. El manejo de esta infección sigue presentando puntos de controversia, tanto en la elección del mejor método diagnóstico como en el tratamiento. En los casos en los cuales la infección por este agente fue confirmada la primera y más efectiva medida es suspender la antibioticoterapia que el paciente este recibiendo, en la medida de lo posible. El tratamiento se basa en tres agentes clásicos: metronidazol, vancomicina y teicoplanina con la más reciente adición de fidaxomicina y ridinilazol. Pacientes con presentación severa muchas veces requieren resolución quirúrgica además de las medidas de soporte y monitoreo. El objetivo de esta revisión es ofrecer información actualizada sobre la patogénesis y estrategias terapéuticas sobre el manejo de la infección por este patógeno.
Abstract:Clostridium difficile infection is the leading cause of hospital acquired diarrhea. The patients can be asymptomatic carriers or present a mild diarrhea, a pseudomembranous colitis, toxic megacolon, sepsis and death. There is controversy in this infection's including the best method of diagnosis and also regarding therapeutic regimen.In cases in which Clostridium infection is confirmed, the first and most effective measure is the withdrawal of any antibiotic treatment the patient is receiving, if possible. The antimicrobial treatment is based on three classic agents: metronidazole, vancomycin and teicoplanin, along with the recent addition of fidaxomicin and ridinilazol.Patients presenting serious symptoms, in addition to appropriate support and monitoring measures, may require surgical treatment. This review's aim is to provide an update on the pathogenesis, and therapeutic strategies on the management of this pathogen.
Assuntos
Humanos , Enterocolite Pseudomembranosa , Vancomicina/uso terapêutico , Clostridioides difficile/virologia , Infecções por Clostridium , Teicoplanina/uso terapêutico , Colite , Diarreia , Disenteria , Metronidazol/uso terapêuticoRESUMO
BACKGROUND: Factors associated with complicated Clostridium difficile infection (CDI) may vary among populations, and predictors of severe outcomes in CDI have not been studied in Hispanic patients. The aim of this study was to identify factors associated with a higher risk of colectomy, all-cause mortality, and CDI-associated mortality in a Hispanic population. METHODS: We performed a retrospective study of all hospitalized patients with a diagnosis of CDI between January 1, 2011 and September 30, 2015 in a 450-bed teaching hospital in Monterrey, northeast Mexico. Three main outcomes were defined: fulminant colitis with subsequent colectomy, all-cause mortality within 30 days of diagnosis, and CDI-attributable mortality. RESULTS: Of 261 patients with diarrhea, 176 were diagnosed with CDI. For colectomy, Charlson comorbidity index, ICU stay and mechanical ventilation prior to CDI diagnosis, days with diarrhea prior to treatment, total days of hospital stay and days after CDI diagnosis, elevated ATLAS score, days of diarrhea post CDI treatment, and treatment failure significantly predicted the necessity of surgical treatment with colectomy. CONCLUSION: Treatment failure, persistent diarrhea, and a high ATLAS score were identified as risk factors for severe outcomes of CDI. A low albumin concentration and high creatinine were associated with higher overall mortality.
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Clostridioides difficile , Infecções por Clostridium , Colectomia , Colite/microbiologia , Colite/cirurgia , Albuminas/deficiência , Colite/mortalidade , Creatinina/sangue , Diarreia , Feminino , Hispânico ou Latino/estatística & dados numéricos , Hospitais de Ensino/estatística & dados numéricos , Humanos , Masculino , México/epidemiologia , Estudos Retrospectivos , Risco , Fatores de RiscoRESUMO
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.
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Humanos , Antibacterianos/uso terapêutico , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/cirurgia , Transplante de Microbiota Fecal , Aminoglicosídeos/uso terapêutico , Clostridioides difficile , Enterocolite Pseudomembranosa/tratamento farmacológico , Enterocolite Pseudomembranosa/cirurgiaRESUMO
The aim of this meta-analysis was to compare the efficacy of metronidazole and vancomycin for the treatment of Clostridium difficile infection, especially to investigate which agent was superior for treating either mild or severe C. difficile infection. A meta-analysis of randomized controlled trials and cohort studies identified in Pubmed, Embase, and the Cochrane Library was conducted. Four randomized controlled trials and two cohort studies involving 1218 patients were included in this meta-analysis. Metronidazole was inferior to vancomycin for treating C. difficile infection in terms of both initial clinical cure rates (risk ratio, RR=0.91, 95% confidence interval, CI=0.84-0.98, p=0.02) and sustained cure rates (RR=0.88, 95% CI=0.82-0.96, p=0.003). For mild C. difficile infection, the efficacy of metronidazole and vancomycin resulted in similar clinical cure rates (RR=0.94, 95% CI=0.84-1.04, p=0.21) and sustained cure rates (RR=0.93, 95% CI=0.83-1.05, p=0.26). For severe C. difficile infection the efficacy of vancomycin was superior to metronidazole in terms of clinical cure rates (RR=0.81, 95% CI=0.69-0.95, p=0.009), whereas sustained cure rates were similar (RR=0.86, 95% CI=0.72-1.02, p=0.08). Regarding microbiological cure metronidazole therapy was as effective as vancomycin therapy (RR=0.88, 95% CI=0.64-1.21, p=0.43). Recurrence rates with metronidazole and vancomycin for both mild C. difficile infection (RR=0.95, 95% CI=0.56-1.60, p=0.85) and severe C. difficile infection (RR=1.27, 95% CI=0.85-1.91, p=0.25) were not different. Likewise, no difference in all-cause mortality was found as well (RR=0.87, 95% CI=0.56-1.35, p=0.53). In conclusion, vancomycin provides improved initial clinical and sustained cure rates in patients with C. difficile infection compared with metronidazole, especially in patients with severe C. difficile infection. In view of these data, vancomycin may be considered first line therapy for severe C. difficile infection.
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Antibacterianos/uso terapêutico , Clostridioides difficile , Infecções por Clostridium/tratamento farmacológico , Diarreia/microbiologia , Metronidazol/uso terapêutico , Vancomicina/uso terapêutico , Estudos de Coortes , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do TratamentoAssuntos
Antiácidos/efeitos adversos , Clostridioides difficile , Infecções por Clostridium/induzido quimicamente , Clostridioides difficile/patogenicidade , Infecções por Clostridium/epidemiologia , Humanos , Prescrição Inadequada/efeitos adversos , Pediatria , Inibidores da Bomba de Prótons/efeitos adversos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: To study the trend of Clostridium difficile infection (CDI) and risk factors for hospital acquired CDI (HA-CDI) among children with cancer. STUDY DESIGN: We analyzed 33â095 first pediatric hospitalizations for malignancy among 43 pediatric hospitals between 1999 and 2011. The effect of demographics, disease characteristics, and weekly drug exposure (antibiotics, antacids, and chemotherapy) on HA-CDI was assessed with multivariate Cox regression. CDI was defined by the combination of International Classification of Diseases, 9th edition-Clinical Modification (ICD-9CM), CDI diagnostic assay billing code, and concurrent administration of a CDI-active antibiotic. HA-CDI was defined as CDI with assay occurring after the sixth hospital day. RESULTS: A total of 1736 admissions with CDI were identified, of which 380 were HA-CDI. CDI incidence increased from 1999-2006 (P = .01); however, CDI testing frequency and disease decreased from 2006-2010 (P < .05). Admissions with HA-CDI had longer lengths of stay compared with those without HA-CDI (35 days vs 12 days, P < .01) and greater risk of inpatient mortality (relative risk 2.3, P < .01). Increased risk of HA-CDI (hazard ratio [95% CI]) was seen after exposure to the following drugs: aminoglycoside (1.357 [1.053-1.749]), third generation cephalosporin (1.518 [1.177-1.959]), cefepime (2.383 [1.839-3.089]), and proton pump inhibiting agent (1.398 [1.096-1.784]) in the prior week, and chemotherapy (1.942 [1.491-2.529]) in the 8-14 days prior to HA-CDI onset. Histamine-2 receptor antagonist exposure in the prior week was associated with decreased risk of HA-CDI (0.730 [0.584-0.912]). CONCLUSIONS: Despite an apparent decrease in CDI incidence from 2006-2010, HA-CDI remains prevalent and morbid among children with cancer. Recent exposure to chemotherapy, proton pump inhibitor, and certain antibiotics were independent risk factors for HA-CDI.
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Clostridioides difficile , Infecções por Clostridium/etiologia , Infecção Hospitalar/etiologia , Neoplasias/complicações , Adolescente , Criança , Pré-Escolar , Infecções por Clostridium/epidemiologia , Estudos de Coortes , Infecção Hospitalar/epidemiologia , Bases de Dados Factuais , Feminino , Hospitais Pediátricos , Humanos , Incidência , Lactente , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Clostridium difficile has become an important healthcare-associated infection due to increased frequency, mortality and recurrence rate. These facts, associated in part to the appearance of epidemic strains have driven changes in diagnostic and therapeutic approaches. The clinical spectrum of C. difficile infection (CDI) ranges from mild diarrhea without systemic compromise to life-threatening pseudomembranous colitis. Metronidazole is the first line treatment in mild CDI; however, the response rate is lower in severe disease, therefore in patients with clinical markers of unfavorable outcome, the first line treatment is oral vancomicin. On the other hand, the increased recurrence rate seen in the last decade with its clinical and economic consequences has forced the development of new therapies that allow change the course of this disease. In this line, the fecal microbiota transplantation and new antibiotics as fidaxomicin has proved to decrease the recurrences.
Clostridium difficile es actualmente una de las principales infecciones asociadas a la atención de salud debido al aumento de su frecuencia, letalidad y capacidad de recurrencia. Estos hechos en parte asociados al surgimiento de cepas conocidas como epidémicas han determinado grandes cambios en el enfrentamiento diagnóstico y terapéutico. El espectro clínico de la infección por C. difficile (ICD) abarca desde una diarrea leve sin compromiso sistémico hasta cuadros de colitis pseudomembranosa que pueden ocasionar la muerte. Metronidazol es el tratamiento de elección de la ICD leve; sin embargo, la tasa de respuesta es inferior en cuadros graves, por lo tanto, en pacientes con marcadores de mal pronóstico vancomicina oral es la terapia de primera elección. Por otro lado, la mayor tasa de recurrencia observada en la última década con sus consecuencias clínicas y económicas ha obligado al desarrollo de nuevas terapias que permitan alterar el curso de la enfermedad. En esta línea, el trasplante de microbiota fecal y nuevos antibióticos como fidaxomicina han mostrado efectividad en reducir las recurrencias.