Advances in application of volatile organic compounds in the rapid detection of clostridium difficile infection / 国际儿科学杂志

Clostridium difficile infection(CDI)is a global public health issue and one of the most common pathogenic infections in the community and hospitals, causing varying degrees of diarrhea and pseudomembranous colitis.The current CDI diagnosis is based on the detection of clostridium difficile(CD)associated toxins or toxin encoding genes in patients′ stool, but these traditional microbiological techniques have limitations that may delay disease diagnosis.In clinical and research, CD has a distinct odor "horse barn odor" , which is caused by the volatile organic compounds(VOCs). VOCs in human breath, blood, urine and feces have recently received increased attention as potential noninvasive diagnostic biomarkers for a wide range of diseases, including infectious diseases and digestive tract disorders.It was discovered that VOCs from CD, with their potential characteristic VOCs, contributed to the rapid diagnosis of CDI.In this paper, we review VOCs and their application in the rapid detection of CDI.

Risk Factors of Clostridium difficile Infection in Hospitalized Patients With Diarrhea / 胃肠病学

Background: Clostridium difficile infection (CDI) is the most common cause of hospital-acquired diarrhea and an important cause of death in hospitalized patients with diarrhea. However, there are not sufficient clinical researches on the risk factors of CDI. Aims: To investigate the risk factors of CDI in hospitalized patients with diarrhea. Methods: A total of 230 hospitalized diarrhea patients who received Clostridium difficile test from January 2015 to January 2019 at the Second Hospital of Hebei Medical University were collected. The patients were divided into CDI group and non-CDI group. Logistic regression analysis was performed to investigate the risk factors of CDI. Results: Compared with non-CDI group, patients in CDI group had a longer hospital stay (P<0.05) and a higher proportion of surgery in the past 6 months (P<0.05). The number of comorbidities in CDI group was higher than that in non-CDI group (P<0.05), and the ratio of gastrointestinal disease, cardiovascular disease, blood/immune system disease, nervous system disease in CDI group were higher than those in non-CDI group (P<0.05). Multivariate analysis showed the number of comorbidities (OR=3.215, 95% CI: 1.576-4.743; P=0.003), gastrointestinal disease (OR=4.135, 95% CI: 3.048-11.416; P=0.000), surgical history (OR=6.734, 95% CI: 2.692-15.849; P=0.000) and antibiotic use (OR=5.996, 95% CI: 2.173-15.481; P=0.000) were risk factors of CDI, especially the use of quinolone antibiotics (OR=4.769, 95% CI: 2.138-14.757; P=0.000). Conclusions: CDI can prolong the hospital stay of patients with diarrhea. Number of comorbidities, underlying gastrointestinal disease, recent history of surgery and antibiotic use, especially the use of quinolone antibiotics are risk factors of CDI in hospitalized patients with diarrhea.

In Silico Screening of DNA Gyrase B Potent Flavonoids for the Treatment of Clostridium difficile Infection from PhytoHub Database

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.

Advances in Study on Role of Reconstructing Intestinal Flora Homeostasis in Treatment of Clostridium difficile Infection / 胃肠病学

Clostridium difficile infection (CDI) is a growing public health concern worldwide. Antibiotics are currently the preferred treatment for CDI, but the heavy use of antibiotics has resulted in the emergence of highly resistant strains of Clostridium difficile and recurrent CDI. More and more studies show that restoring intestinal flora homeostasis is an important strategy for the treatment of CDI. This article reviewed the relationship between intestinal flora homeostasis and CDI, and the treatment strategies for CDI by restoring intestinal flora homeostasis.

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)

Diagnosis and treatment of recurrent clostridium difficile infection in children / 国际儿科学杂志

Clostridium difficile (CD),a gram-positive,spore-forming,obligate anaerobic bacillus,is a leading cause of antibiotic-associated diarrhea (AAD) worldwide.With the widespread use of broad-spectrum antibiotics,the incidence of clostridium difficile infection in children is rising,while recurrent clostridium difficile infection (RCDI) requires prolonged treatment and higher medical costs.Malignancy,recent surgery and antibiotic exposures have been identified as the risk factors in children.While the toxigenic strains culture and the cell cytotoxicity neutralization assay are gold standard for the diagnosis,new diagnostic approaches such as nucleic acid amplification method have become available.The use of antibiotics,fecal microbiota transplantation (FMT) or monoclonal antibodies are included in the current treatments for RCDI.This review will cover published studies to discuss the risk factors,diagnosis and treatment of RCDI in children.

Advances in research of fecal bacteria transplantation in inflammatory bowel disease / 医学研究生学报

Inflammatory bowel disease (IBD) is a chronic, nonspecific, inflammatory bowel disease that has not been completely elucidated yet. In recent years, the role of gut flora in the pathogenesis and prognosis of IBD has drawn more and more attention. Fecal Bacterial Transplantation (FMT) referred to transplanting healthy human gut flora into the patient's gastrointestinal tract and reconstitutes a functioning gut flora. Many studies have shown that FMT is effective in treatment of IBD. This brings new hope to IBD patients with poor clinical drug treatment. The applications and precautions of FMT in IBD are reviewed.

Fecal Microbiota Transplantation: An Update on Clinical Practice

Fecal microbiota transplantation (FMT) is an infusion in the colon, or the delivery through the upper gastrointestinal tract, of stool from a healthy donor to a recipient with a disease believed to be related to an unhealthy gut microbiome. FMT has been successfully used to treat recurrent Clostridium difficile infection (rCDI). The short-term success of FMT in rCDI has led to investigations of its application to other gastrointestinal disorders and extra-intestinal diseases with presumed gut dysbiosis. Despite the promising results of FMT in these conditions, several barriers remain, including determining the characteristics of a healthy microbiome, ensuring the safety of the recipient with respect to long-term outcomes, adequate monitoring of the recipient of fecal material, achieving high-quality control, and maintaining reasonable costs. For these reasons, establishing uniform protocols for stool preparation, finding the best modes of FMT administration, maintaining large databases of donors and recipients, and assuring that oral ingestion is equivalent to the more widely accepted colonoscopic infusion are issues that need to be addressed.

Laboratory Diagnosis of Clostridium difficile Infection in Korea: The First National Survey

In May 2015, we conducted a voluntary online survey on laboratory diagnostic assays for Clostridium difficile infection (CDI) across clinical microbiology laboratories in Korea. Responses were obtained from 66 laboratories, including 61 hospitals and five commercial laboratories. Among them, nine laboratories reported having not conducted CDI assays. The toxin AB enzyme immunoassay (toxin AB EIA), nucleic acid amplification test (NAAT), and C. difficile culture, alone or in combination with other assays, were used in 51 (89.5%), 37 (64.9%), and 37 (64.9%) of the remaining 57 laboratories, respectively, and 23 (40.4%) of the laboratories performed all three assays. Only one laboratory used the glutamate dehydrogenase assay. Nine laboratories used the toxin AB EIA as a stand-alone assay. The median (range) of examined specimens in one month for the toxin AB EIA, NAAT, and C. difficile culture was 160 (50–2,060), 70 (7–720), and 130 (9–750), respectively. These findings serve as valuable basic data regarding the current status of laboratory diagnosis of CDI in Korea, offering guidance for improved implementation.

Drug Use Evaluation of Clostridium difficile Infection in Elderly Patients and Risk Factors of Non-improving Group

OBJECTIVE: Clostridium difficile Infection (CDI) is one of the common nosocomial infections. As elderly population increases, the proper treatment has been emphasized. We investigated the risk factors associated with CDI unimprovement in elderly patients. Furthermore, we performed drug use evaluation of old CDI patients and oldest-old CDI patients. METHODS: It was a retrospective study using electronic medical record at Kangbuk Samsung Medical Center (KBSMC) from January 2016 to December 2017. Seventy three patients aged 65 years or older, diagnosed with CDI by Clostridium difficile Toxin B Gene [Xpert] were screened and they were assessed for risk factors regarding unimprovement status. We also evaluated drug use evaluation in old patients (65≤age<80) and oldest-old patients (80≤age) by assessing the use of initial therapy, severity, dose, route, treatment course, days of use, total days of use and treatment outcome of initial therapy. RESULTS: Out of 73 patients aged over 65 years, four patients were excluded because they did not receive any treatment. There were 31 improved patients and 38 unimproved patients after initial therapy. We were able to find out patients with surgical comorbidity or endocrine comorbidity (especially, diabetes mellitus) had 2.885 more risk of becoming unimproved than those patients without surgical comorbidity or endocrine comorbidity. Drug use evaluation for CDI was generally fair, but vancomycin as initial therapy is more recommended than metronidazole. CONCLUSION: Although age, antibiotics exposure, use of antacids are all important risk factors for CDI, our result did not show statistical significance for these risk factors. However, the study is meaningful because the number of elderly population keeps increasing and recently updated guideline suggests the use of vancomycin as drug of choice for CDI.

Rapid and accurate diagnosis of Clostridium difficile infection by real-time polymerase chain reaction

BACKGROUND/AIMS: The incidence and severity of Clostridium difficile infection (CDI) have increased worldwide, resulting in a need for rapid and accurate diagnostic methods. METHODS: A retrospective study was conducted to compare CDI diagnosis methods between January 2014 and December 2014. The stool samples, which were obtained in presumptive CDI patients, were compared for their diagnostic accuracy and rapidity, including real-time polymerase chain reaction (PCR) of toxin genes, C. difficile toxin assay, and culture for C. difficile. RESULTS: A total of 207 cases from 116 patients were enrolled in this study and 117 cases (56.5%) were diagnosed as having CDI. Among the 117 cases, the sensitivities of real-time PCR, C. difficile toxin assay, and culture for C. difficile were 87.2% (102 cases; 95% CI, 80.7%–92.8%), 48.7% (57 cases; 95% CI, 41.0%–59.8%), and 65.0% (76 cases; 95% CI, 60.2%–78.5%), respectively (P < 0.005). Notably, 34 cases (29.0%) were diagnosed with CDI by real-time PCR only. The time required to obtain results was 2.27 hours (136.62±82.51 minutes) for real-time PCR, 83.67 hours (5,020.66±3,816.38 minutes) for toxin assay, and 105.79 hours (6,347.68±3,331.46 minutes) for culture (P < 0.005), respectively. CONCLUSIONS: We confirmed that real-time PCR of toxin genes is the most effective diagnostic method for accurate and early diagnosis of CDI. It also helps to diagnose hypervirulent CDI, such as ribotype 027 infection.

Antibioticoterapia y nuevas terapias no farmacológicas en infecciones por clostridium diffici / Antibiotic therapy and new non-pharmacological therapies in clostridium diffici infections

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.

Fecal microbiota transplantation therapy on Clostridium difficile infection in children / 中华实用儿科临床杂志

With the overuse of antibiotics,Clostridium difficile infections are increasing,and the incidence of refractory or recurrent cases increase.Increasing resistance to the traditional treatment(metronidazole and/or vancomycin),relapsing Clostridium difficile infection needs to seek new treatments.Fecal microbiota transplantation has been widely used in the treatment of adult Clostridium difficile infection,but is seldom used in children.In this paper,fecal microbiota transplantation for the treatment of Clostridium difficile infection in children related issues were reviewed.

Fecal Calprotectin Level Reflects the Severity of Clostridium difficile Infection

Clostridium difficile is a significant nosocomial and community-acquired pathogen, and is the leading cause of antibiotic-induced diarrhea associated with high morbidity and mortality. Given that the treatment outcome depends on the severity of C. difficile infection (CDI), we aimed to establish an efficient method of assessing severity, and focused on the stool biomarker fecal calprotectin (FC). FC directly reflects the intestinal inflammation status of a patient, and can aid in interpreting the current guidelines, which requires the integration of indirect laboratory parameters. The distinction of 80 patients with CDI versus 71 healthy controls and 30 severe infection cases versus 50 mild cases was possible using FC as a marker. The area under the receiver operating characteristic curves were 0.821 and 0.746 with a sensitivity of 75% and 70% and specificity of 79% and 80%, for severe versus mild cases, respectively. We suggest FC as a predictive marker for assessing CDI severity, which is expected to improve the clinical management of CDI.

Clostridium difficile: desde el metronidazol al trasplante fecal / Clostridium difficile: from metronidazole to fecal transplant

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.

Fecal Microbiota Transplantation: Current Applications, Effectiveness, and Future Perspectives

Fecal microbiota transplantation (FMT) is the infusion of liquid filtrate feces from a healthy donor into the gut of a recipient to cure a specific disease. A fecal suspension can be administered by nasogastric or nasoduodenal tube, colonoscope, enema, or capsule. The high success rate and safety in the short term reported for recurrent Clostridium difficile infection has elevated FMT as an emerging treatment for a wide range of disorders, including Parkinson's disease, fibromyalgia, chronic fatigue syndrome, myoclonus dystopia, multiple sclerosis, obesity, insulin resistance, metabolic syndrome, and autism. There are many unanswered questions regarding FMT, including donor selection and screening, standardized protocols, long-term safety, and regulatory issues. This article reviews the efficacy and safety of FMT used in treating a variety of diseases, methodology, criteria for donor selection and screening, and various concerns regarding FMT.

Clinical Outcomes in Hospitalized Patients with Clostridium difficile Infection by Age Group / 대한소화기학회지

BACKGROUND/AIMS: Advanced age is a known risk factor of poor outcomes for colitis, including Clostridium difficile infection (CDI). The present study compares the clinical outcomes of young and old patients hospitalized for CDI. METHODS: The clinical records of patients admitted from January 2007 to December 2013 with a diagnosis of CDI were analyzed. Patient baseline characteristics, clinical courses, and outcomes were compared with respect to age using a cut-off 65 years. RESULTS: Of the 241,391 inpatients registered during the study period, 225 (0.1%) with a diagnosis of CDI were included in the study. The mean patient age was 67.7 years. Seventy-two patients (32.0%) were younger than 65 years and 153 patients (68.0%) were 65 years old or more. The male to female ratio in the younger group was 0.8, and 0.58 in the older group. All 225 study subjects had watery diarrhea; six patients (8.3%) complained of bloody diarrhea in the young group and 21 patients (13.7%) in the old group (p=0.246). Right colon involvement was more common in the old group (23.5% vs. 42.7%, p=0.033). Furthermore, leukocytosis (41.7% vs. 67.3%, p=0.000), a CDI score of > or =3 points (77.8% vs. 89.5%, p=0.018), and hypoalbuminemia (58.3% vs. 76.5%, p=0.005) were more common in the old group. Failure to first line treatment was more common in the old group (17 [23.6%] vs. 58 [37.9%], p=0.034). CONCLUSIONS: Severe colitis and failure to first line treatment were significantly more common in patients age 65 years or more. More aggressive initial treatment should be considered for older CDI patients.

Gastrointestinal disorders in children treated with fecal microbiota transplantation / 中华实用儿科临床杂志

Fecal microbiota transplantation (FMT) is a therapy with at least 1 700 years in the world medical history.In recent years,FMT has gained rapidly development.The recent studies demonstrated that FMT has obvious clinical efficacy and safety on the treatment of Clostridium difficile infection,inflammatory bowel disease and other diseases in adult.The present article will discuss efficacy of FMT in treating digestive diseases in children.

Current advances related to Clostridium difficile infection.

Clostridium difficile infection (CDI) can trigger various responses, ranging from asymptomatic carriage to fulminant colitis. Hard-to-cure CDI, such as severe CDI, multiple recurrences of CDI, refractory CDI, and hypervirulent strains of C. difficile, require new treatments, although antibiotics such as metronidazole and vancomycin are the treatment of choice for initial and first relapsing CDI. Active immunization with C. difficile toxins and faecal microbiota transplantation deserve special attention. Here we describe these strategies for difficult-to-treat CDI.

A Case of Toxic Megacolon Caused by Clostridium difficile Infection and Treated with Fecal Microbiota Transplantation

Toxic megacolon is a rare clinical complication of fulminant Clostridium difficile infection. The mortality rate of fulminant C. difficile infection is reported to be as high as 50%. Fecal microbiota transplantation is a highly effective treatment in patients with recurrent or refractory C. difficile infection. However, there are few published articles on the use of such transplantation for fulminant C. difficile infection. Here, we report on a patient with toxic megacolon complicated by C. difficile infection who was treated successfully with fecal microbiota transplantation.