Clostridium Difficile-associated Infection Research Articles

Клинический случай атипичного течения инфекции Clostridium difficile в сочетании с энтеробиозом у мальчика 14 лет

Clostridium difficile infection is currently a serious medical and epidemiological problem due to a significant and steady increase in the incidence of this pathology. An important causal factor in the increased incidence of Clostridium difficile infection is a widespread and often uncontrolled use of antibiotic therapy. The difficulty in diagnosing Clostridium difficile lies in a wide range of clinical manifestations of this infection, from mild diarrhea to pseudomembranous colitis, toxic megacolon, colon perforation, and multiple organ failure, resulting in a high mortality rate and prolonged length of stay in intensive care units. This article presents a clinical case of Clostridium difficile-associated infection in a 14-year-old boy. An important diagnostic feature of this case is the chronic course of infection, the clinical picture being dominated by pain, hyperthermia, and intoxication without diarrhea, as well as the presence of enterobiasis. This clinical example shows that Clostridium difficile-associated infection does not always present with diarrhea. The etiology of the disease in this case was confirmed not only by the detection of specific Clostridium difficile toxins in the patient’s stool samples, but also by clear positive dynamics with the administration of etiotropic therapy. This article describes the stages of differential diagnostic search and the choice of treatment tactics for Clostridium difficile infection. Key words: clostridium infection, children

Pharmacological, Toxicological, and Dose Range Assessment of OG716, a Novel Lantibiotic for the Treatment of Clostridium difficile-Associated Infection.

Lantibiotics present an attractive scaffold for the development of novel antibiotics. We report here a novel lantibiotic for the treatment of Clostridium difficile infection. The lead compounds were selected from a library of over 700 single- and multiple-substitution variants of the lantibiotic mutacin 1140 (MU1140). The best performers in vitro and in vivo were further used to challenge Golden Syrian hamsters orally in a Golden Syrian hamster model of Clostridium difficile-associated disease (CDAD) in a dose-response format, resulting in the selection of OG716 as the lead compound. This lantibiotic was characterized by a 50% effective dose of 23.85 mg/kg of body weight/day (10.97 μmol/kg/day) in this model. Upon oral administration of the maximum feasible dose (≥1,918 mg/kg/day), no observable toxicities or side effects were noted, and no effect on intestinal motility was observed. Compartmentalization to the gastrointestinal tract was confirmed. MU1140-derived variants offer a large pipeline for the development of novel antibiotics for the treatment of several indications and are particularly attractive considering their novel mechanism of action. Based on the currently available data, OG716 has an acceptable profile for further development for the treatment of CDAD.

Clostridium Difficile-Associated Infection in Trauma Patients: Development of the Clostridium Difficile Influencing Factors (CDIF) Score.

Clostridium difficile-associated infection (CDAI) can result in longer hospitalization, increased morbidity, and higher mortality rates for surgical patients. The impact on trauma patients is unknown, however. To assess the effect of CDAI on trauma patients and develop a scoring system to predict CDAI in that population. Records of all trauma patients admitted to a Level I Trauma Center from 2001 to 2014 were retrospectively reviewed. Presence of CDAI was defined as evidence of positive toxin or polymerase chain reaction. Patients with CDAI were matched to patients without CDAI using propensity score matching on a ratio of 1:3. Primary outcome was inhospital mortality. Secondary outcomes included length of stay and need for mechanical ventilation. A decision-tree analysis was performed to develop a predicting model for CDAI in the study population. During the study period, 11,016 patients were identified. Of these, 50 patients with CDAI were matched to 150 patients without CDAI. There were no differences in admission characteristics and demographics. Patients in whom CDAI developed had significantly higher mortality (12% vs 4%, p < 0.01), need for mechanical ventilation (57% vs 23%, p < 0.01), and mean hospital length of stay (15.3 [standard deviation 1.4]) days vs 2.1 [0.6] days, p < 0.0). In trauma patients, CDAI results in significant morbidity and mortality. The C difficile influencing factor score is a useful tool in identifying patients at increased risk of CDAI.

Первый опыт успешного лечения псевдомембранозного колита аутоштаммами лактобацилл

Aim: to imply a method of Clostridium (Clostridioides) difficile-associated infection treatment based on lactobacilli autostrains. Materials and methods: Toxin-producing vancomycin-resistant C. difficile and three types of lactobacilli in different titers were isolated from the translucent feces of a patient with recurrent C. difficile-associated infection. According to the results of the study, the strain Lactobacillus zeae was detected, which showed high antagonistic activity against C. difficile. Within 48 hours, biomass of L. zeae was accumulated. The patient was administered a suspension of lactobacilli per rectum (in the form of microclysters) every other day. Results: in a patient with severe pseudomembranous colitis, a persistent remission of the underlying disease was achieved against the background of regular injections of a suspension of Lactobacillus zeae autostrains with a high antagonistic activity against C. difficile, isolated in this patient. Conclusion: Lactobacillus transplantation is an effective and promising treatment for recurrent clostridial infection resistant to antibiotic therapy.

De-Escalation of Antimicrobials in Adult Hematopoietic Cell Transplantation Recipients with Febrile Neutropenia of Unknown Origin

De-Escalation of Antimicrobials in Adult Hematopoietic Cell Transplantation Recipients with Febrile Neutropenia of Unknown Origin

Detection of toxigenic Clostridium difficile in paediatric patients

IntroductionOur main objective was a revision of clinical, microbiological and epidemiological results of Clostridium difficile-associated infection in paediatric patients (2010–2015). We compared the diagnoses performed by detection of toxins in faeces and those performed by real-time PCR. MethodsThis retrospective study included 82 paediatric patients. Detection of toxigenic C. difficile was performed sequentially, in diarrheal faeces and under clinical request. ResultsA total of 39% of the patients were attended at Haematology–Oncology Unit and >50% of them had previously received cephalosporins. Fever associated with diarrhoea was more frequent in the group of toxin detection, whereas not receiving specific antibiotic treatment was more frequent in the group of positive PCR, without statistically significant differences. ConclusionsWe highlight the presence of C. difficile infection in children under 2 years old. A diagnostic testing in selected paediatric patients would be advisable when there is clinical suspicion of infection.

Detección de Clostridium difficile toxigénico en pediatría

IntroductionOur main objective was a revision of clinical, microbiological and epidemiological results of Clostridium difficile-associated infection in paediatric patients (2010-2015). We compared the diagnoses performed by detection of toxins in feces and those performed by real-time PCR. MethodsThis retrospective study included 82 paediatric patients. Detection of toxigenic C. difficile was performed sequentially, in diarrheal feces and under clinical request. ResultsA total of 39% of the patients were attended at Haematology-oncology Unit and >50% of them had previously received cephalosporins. Fever associated with diarrhea was more frequent in the group of toxin detection, whereas not receiving specific antibiotic treatment was more frequent in the group of positive PCR, without statistically significant differences. ConclusionsWe highlight the presence of C. difficile infection in children under 2years old. A diagnostic testing in selected paediatric patients would be advisable when there is clinical suspicion of infection.

The actual condition of laboratory diagnostic of Clostridium difficile-associated diarrhea; the methods of detection of toxigenic strains (review of publications).

The Clostridium difficile-associated infection (CDI) is one of the main causes of nosocomial diarrhea. The complicacy of laboratory diagnostic results in progression of disease bringing on extensive inflammatory alterations in the wall of large intestine and characterizing by superficial necrosis of mucous membrane with development of "pseudo-membranes" resulting in development of toxic megacolon, perforation of intestinal wall, peritonitis and sepsis. The main role in diagnosing plays indication of agent and detection of its toxins. None of laboratory tests can be applied as an independent technique of laboratory diagnostic of CDI. The multi-step diagnostic can become an appropriate strategy for quick and full detection of antibiotic-associated diarrhea.

Influence of antibiotics and case exposure on hospital-acquired Clostridium difficile infection independent of illness severity

Previous studies of the association between antibiotic exposure and risk of hospital-acquired Clostridium difficile-associated infection (CDI) have not fully accounted for patient severity of illness, and competing risks. To determine the potential effects of interventions on hospital-acquired CDI risk. All adults admitted to a teaching hospital between 2004 and 2014 for more than two days were included. Exposures to all antibiotics and cases of CDI were determined. Patients were followed until discharge from hospital, death, or acquisition of hospital-acquired CDI (defined as positive toxin assay in unformed stool >2 days following admission). Multivariable proportional hazards competing-risks modelling with time-dependent covariates was used, accounting for patient severity of illness using the Escobar model. In all, 208,104 patients were studied. Hospital-acquired CDI risk was 0.46 events per 1000 patient-days, decreasing significantly during the study period. Compared to the 5th percentile hospital death risk (0.02%), patients with a 50% risk of death in hospital hadan adjusted hazard ratio (aHR) of hospital-acquired CDI of 5.5. Exposure to some antibiotics significantly increased hospital-acquired CDI risk, being highest for carbapenems (aHR: 1.47 after one week of continuous exposure) and intravenous vancomycin (aHR: 1.53). On the ward, sharing a room with other patients newly diagnosed with CDI significantly increased the risk of subsequent disease (aHR: 1.16 on CDI diagnosis day). The primary determinant of hospital-acquired CDI was patient severity of illness. Exposure to both antibiotics and other patients with CDI significantly increased the subsequent risk of hospital-acquired CDI but this risk was small relative to patient severity of illness.

Clostridium difficile Infections after Blunt Trauma: A Different Patient Population?

The epidemiology of Clostridium difficile-associated infection (CDI) has changed, and it is evident that susceptibility is related not only to exposures and bacterial potency, but host factors as well. Several small studies have suggested that CDI after trauma is associated with a different patient phenotype. The purpose of this study was to examine and describe the epidemiologic factors associated with C. difficile in blunt trauma patients without traumatic brain injury using the Trauma-Related Database as a part of the "Inflammation and Host Response to Injury" (Glue Grant) and the University of Florida Integrated Data Repository. Previously recorded baseline characteristics, clinical data, and outcomes were compared between groups (67 C. difficile and 384 uncomplicated, 813 intermediate, and 761 complicated non-C. difficile patients) as defined by the Glue Grant on admission and at days seven and 14. The majority of CDI patients experienced complicated or intermediate clinical courses. The mean ages of all cohorts were less than 65 y and CDI patients were significantly older than uncomplicated patients without CDI. The CDI patients had increased days in the hospital and on the ventilator, as well as significantly higher new injury severity scores (NISS), and a greater percentage of patients with NISS >34 points compared with non-CDI patients. They also had greater Marshall and Denver multiple organ dysfunction scores than non-CDI uncomplicated patients, and greater creatinine, alkaline phosphatase, neutrophil count, lactic acid, and PiO2:FiO2 compared with all non-CDI cohorts on admission. In addition, the CDI patients had higher glucose concentrations and base deficit from uncomplicated patients and greater leukocytosis than complicated patients on admission. Several of these changes persisted to days seven and 14. Analysis of severe blunt trauma patients with C. difficile, as compared with non-CDI patients, reveals evidence of increased inflammation, immunosuppression, worse acute kidney injury, higher NISS, greater days in the hospital and on the ventilator, higher organ injury scores, and prolonged clinical courses. This supports reports of an increased prevalence of CDI in a younger population not believed previously to be at risk. This unique population may have specific genomic or inflammation-related risk factors that may play more important roles in disease susceptibility. Prospective analysis may allow early identification of at-risk patients, creation of novel therapeutics, and improved understanding of how and why C. difficile colonization transforms into infection after severe blunt trauma.

Performance of prognostic index in severe Clostridium difficile-associated infection: retrospective analysis in a university hospital

By consensus severe, Clostridium difficile-associated infection (CDAI) is one that results in hospitalization in ICU, colectomy or death within 30 days. Multiple prognostic indices (IP) attempt to predict these adverse events. To evaluate the performance of 4 PI in predicting severe CDI. Hospitalized patients ≥ 18 years old with ICD were retrospectively evaluated. Patients with recurrent infection or hematological cancer were excluded. Four PI were evaluated: UPMC version 1, Calgary version 1, Hines VA and Calgary version 2. Seven of 81 patients (8.1%) met the definition of severe CDI. Positive predicted value (PPV) and negative predicted value (NPV) of PI ranged from 20-75% and 91.3-95.7%, respectively. Only Hines VA index had a satisfactory Kappa index (0.74; 95% CI 0.41-1) with a PPV of 75% and NPV of 95,7%. However, because of the variables included, this PI could be calculated only in 32.6% of patients. Hines VA index has the best predicted value and agreement to rule out a severe CDI. Like others PI it has the limitation of including difficult variables to assess in all patients and tends to overestimate an unfavorable course.

Recurrent Clostridium difficile infection: The scope of the problem and management decisions

Clostridium difficile-associated infection is a growing problem worldwide, contributing to increased morbidity and mortality. More recently, there have been epidemics of C. difficile-associated disease in the United States and Canada with emergence of a hypervirulent NAP1/BI/027 strain (Loo et al., 2005).1 As many as 35% of patients develop recurrent C. difficile-associated disease after an initial episode. Of these patients, 50%–65% have multiple recurrences of C. difficile infection (McFarland et al., 2002).2 Still other patients develop refractory or life-threatening fulminant C. difficile colitis despite standard antibiotic treatment. In this article, we review the problem of recurrent and refractory C. difficile-associated disease, with particular emphasis on treatment options. Topics include available pharmacological treatment, fecal microbiota transplantation, and lesser-used treatment options.

Clostridium difficile–associated infection: a disease of varying severity

Clostridium difficile-associated infection (CDI) can have varying severity from asymptomatic carriage to fulminant colitis. Its incidence and virulence in North America are increasing. The increase in virulence is associated with emergence of the highly toxigenic North American pulsed field gel electrophoresis-1 strain. The major risk factor for CDI is exposure to antibiotics. Another major risk factor is hospitalization. The spectrum of CDI ranges from asymptomatic carriers to fulminant disease. Although asymptomatic carriers require no treatment, fulminant disease carries a substantial mortality regardless of management strategy.

Fecal Bacteriotherapy Works for Clostridium difficile Infection — A Metaanalysis

Purpose:Clostridium difficile-associated infection (CDI) is a serious condition that usually follows antibiotic therapy. In the majority of cases, it is effectively treated with oral vancomycin or metronidazole; nevertheless, the infection has a high relapse rate (40%). Case-series and case-reports show fecal bacteriotherapy has been used to treat these patients with promising results. However, there are no large studies to provide evidence for the efficacy of this therapy. The aim of this meta-analysis was to determine the efficacy of fecal transplant in CDI. Methods: We performed a literature search from 1947 to 2011, using Medline and SCOPUS. Reports published in English literature only were included in the review. Individual patient data were obtained from each study and case-reports. Exclusion criteria were: 1. Patient age ≤ 18 years; 2. Indication other than CDI; and 3. Use of non-fecal source. In circumstances where individual patient data was not reported in the publication, study sponsors were contacted to obtain the data. The primary endpoint was to assess the rate of diarrhea resolution. Secondary endpoints were to identify variables associated with treatment failure and side-effects of therapy. Results: A total of 16 published articles were included in the analysis, which included 7 case-reports and 9 case-series or clinical studies. A total of 148 patients (mean age = 66 years) had received fecal bacteriotherapy for CDI. Follow-up ranged from 10 days to 62 months after the transplant (Mean= 12 months). Fecal transplant had an overall success rate of 85.4%. On univariate analysis, shorter duration of symptoms before fecal bacteriotherapy (<60 days) and naso-duodenal route were associated with treatment failure. The source of feces donor and administration of various pretreatment agents had no association with the outcome of the treatment. On multivariate regression analysis, shorter duration of symptoms (<60 days) before the fecal bacteriotherapy (LR-7.12; p= 0.01) was associated with treatment failure. The only reported adverse events following fecal bacteriotherapy were a solitary case each of irritable bowel syndrome and suspected peritonitis following the transplant. Conclusion: Fecal bacteriotherapy is a safe and effective treatment option for CDI. Early fecal bacteriotherapy (<60 days after onset of symptoms) was associated with treatment failure.

Molecular Epidemiology of Clostridium difficile Strains in Children Compared with That of Strains Circulating in Adults with Clostridium difficile-Associated Infection

Molecular analysis of Clostridium difficile (28 isolates) from children (n = 128) in Oxfordshire, United Kingdom, identified eight toxigenic genotypes. Six of these were isolated from 27% of concurrent adult C. difficile-associated infections studied (n = 83). No children carried hypervirulent PCR ribotype 027. Children could participate in the transmission of some adult disease-causing genotypes.

Catastrophic Clostridium difficile Enteritis in a Pelvic Pouch Patient: Report of a Case

IntroductionIn recent years, Clostridium difficile-associated infection has emerged as an increasingly problematic entity. More virulent strains have been isolated and new manifestations of the infection have been described. PurposeThe primary aim of this manuscript is to describe what we believe to be the first reported case of devastating C. difficile enteritis in a patient with an ileal reservoir. ConclusionA high index of suspicion is required in the appropriate clinical setting in light of the apparently changing spectrum of C. difficile disease.

Colonization and infection with multiple nosocomial pathogens among patients colonized with vancomycin-resistant Enterococcus.

To test the hypothesis that patients colonized with vancomycin-resistant Enterococcus (VRE) have a higher frequency of colonization or infection with other nosocomial pathogens than do patients who are not colonized with VRE. A rectal swab culture survey was conducted to determine the point-prevalence of stool colonization with ceftazidime-resistant gram-negative bacilli in hospitalized patients with or without VRE stool colonization. For a 6-month period, the frequency of Clostridium difficile diarrhea and isolation of antibiotic-resistant (ie, ceftazidime-, piperacillin/tazobactam-, levofloxacin-, or trimethoprim/sulfamethoxazole-resistant) gram-negative bacilli, methicillin-resistant Staphylococcus aureus (MRSA), and non-albicans Candida species from clinical specimens other than stool was examined. A Department of Veterans Affairs medical center. All patients hospitalized in the acute care facility and one nursing home unit during a 1-week period in February 2001. VRE-colonized patients had a higher point-prevalence of rectal colonization with ceftazidime-resistant gram-negative bacilli than did patients not colonized with VRE (17% vs 4%; P = .026). During a 6-month period,the VRE-colonized patients were more likely to have Clostridium difficile-associated diarrhea (26% vs 2%; P = .001), MRSA infection (17% vs 4%; P = .017), or colonization or infection with gram-negative bacilli resistant to 4 different antibiotics. VRE-colonized patients in our institution have a higher frequency of colonization or infection with other nosocomial pathogens than do patients who are not colonized with VRE. This suggests that isolation measures implemented to control VRE could help limit the dissemination of other, coexisting pathogens.

Rifalazil prevents and treats Clostridium difficile-associated infection in hamsters

Rifalazil prevents and treats Clostridium difficile-associated infection in hamsters

Clostridium difficile toxin B disrupts the barrier function of T84 monolayers

The contribution of toxin B to Clostridium difficile-associated infection is undefined. Toxin B induces dramatic phenotypic alterations (cytotoxic effects) in cultured mesenchymal and nonintestinal epithelial cells, yet its effects on intestinal epithelial cells are not clearly understood. The alterations induced by toxin B in nonintestinal cells appear to be secondary to toxin-induced redistribution of filamentous actin. It has not been determined whether toxin B exerts similar effects on cultured intestinal epithelial cells or whether such phenotypic alterations are of any physiological consequence. To address these questions, we examined the effect of C. difficile toxin B on the phenotype and barrier function of T84 cell monolayers. Our studies show that the cytotoxic effects of toxin B, i.e., cell rounding, do extend to cultured intestinal epithelial cells (T84). In addition, toxin B dramatically reduces the barrier function of T84 monolayers grown on collagencoated filters. Toxin B-induced redistribution of filamentous actin appears to be responsible for the alterations in both intestinal epithelial cell phenotype and barrier function. Specifically, filamentous actin comprising the perijunctional actomyosin ring, known to be important in regulating tight junction permeability, is condensed into discrete plaques. Flux studies confirm that the permeability defect is at the level of the tight junction. We conclude that toxin-induced changes in actin distribution perturb intercellular junctional contacts and thereby ablate epithelial barrier function. There was no evidence of cell death as determined by lactate dehydrogenase release assays.