Severe Pseudomembranous Colitis Research Articles

NKp46+ ILC3s promote early neutrophil defense against Clostridioides difficile infection through GM-CSF secretion

Clostridioides difficile infection (CDI) is a common cause of antibiotic-associated colitis. C. difficile proliferates and produces toxins that damage the colonic epithelium, leading to symptoms ranging from mild diarrhea to severe pseudomembranous colitis. The host's innate response to CDI occurs in two phases: an early phase in which neutrophils reduce the bacterial load and a late phase involving repair mechanisms to restore epithelial integrity. Group 3 innate lymphoid cells (ILC3s) are crucial in protecting the gut from CDI. Previous studies have shown that ILC3-derived IL-22 is essential in the late phase of CDI for epithelial repair and maintaining an intestinal microbiota that competes with C. difficile, preventing its expansion. Our study finds that ILC3s also protect during the early stages of CDI by sustaining neutrophils through GM-CSF. Less neutrophil production, accumulation, and activation was evident in ILC3-deficient mice than in wild-type (WT) mice, which led to exacerbated symptoms, impaired pathogen clearance, a compromised epithelial barrier, and increased mortality. The adoptive transfer of ILC3s into ILC3-deficient mice restored neutrophil responses and improved disease outcomes. Both in vitro and in vivo experiments revealed that GM-CSF production by ILC3s is crucial for neutrophil production and effective resistance during CDI. Using mice lacking NKp46+ ILC3s, we found that this subset significantly contributes to GM-CSF production in CDI. These findings highlight the critical role of the ILC3-neutrophil connection in early innate responses to CDI. Enhancing ILC3 production of GM-CSF could be a promising strategy for improving host defense against CDI and other enteric infections.

S2963 Unraveling Severe Pseudomembranous Colitis in an Elderly Patient with a Complex Medical History

S2963 Unraveling Severe Pseudomembranous Colitis in an Elderly Patient with a Complex Medical History

The post-COVID-19 intestinal damages: clinical, endoscopic and morphological features. The results of a single-center prospective observational cohort study

Background: Clinical signs of gastrointestinal disorders can manifest both from the first days of COVID-19 and after recovery, and may last up to 6 months or more. Most studies examined the gastrointestinal changes in acute coronavirus infection, whereas intestinal abnormalities in the early and late post-COVID period and their causes have not been sufficiently studied.
 Aim: To determine the frequency and types of clinical, endoscopic and morphological abnormalities in patients with post-COVID-19 intestinal lesions.
 Materials and methods: This was a prospective, observational, open-label, cohort, non-controlled study in 72 patients with intestinal symptoms after the coronavirus infection (female 48, mean age 54.6 (95% confidence interval 51.08–58.12) years), who were admitted to the Department of Gastroenterology of general hospital during the first and second waves of COVID-19 from June 2020 to September 2021. The assessment included routine anamnestic, clinical, laboratory, endoscopic, and morphological methods. When indicated, visualization methods (ultrasound, computed tomography, magnetic resonance imaging) were performed. The treatment was symptom-oriented and aimed at inflammation, anemia and protein and electrolyte abnormalities. Outcomes were assessed by the time of discharge from the hospital and thereafter by telephone interviewing of the patients for 8 weeks.
 Results: In all patients, the main symptom was diarrhea, which started right just after SARS-CoV-2 infection with negative PCR test or 2–4 weeks later. The average stool frequency was 6.8 (5.61–7.99) times daily. In 19/72 patients (26.4%), there were blood and mucus in stools. 2.8% of the patients developed massive intestinal bleeding. Fever was present in 40.3% of the patients, decreased hemoglobin levels in 44.4%, and hypoalbuminemia in 16.7%. Signs of systemic inflammation (increased erythrocyte sedimentation rate, C-reactive protein, fibrinogen, thrombocytosis, leukocytosis) were found with various frequencies in a half of the patients. Clostridioides difficile A and B toxins were identified in 38.9% of the cases and increased fecal calprotectin in 22.2%.
 Ileocolonoscopy was performed in 67 patients. The colonic mucosa in 21 (31.3%) patients either was not different from the normal, or showed minimal inflammatory changes such as absence of vascular pattern, hyperemia, mild friability even in patients with severe diarrhea, fever and laboratory abnormalities. Pseudomembranous colitis was diagnosed in 12 (17.9%) patients, and focal hemorrhagic colitis in 11 (16.4%) patients. In 2 (3%) cases, moderate to severe ulcerative colitis was newly diagnosed after the SARS-CoV-2 infection. Single or multiple erosions and ulcers of various sizes against the unchanged surrounding mucosa were found in 19 (28.4%) patients. In 2 (3%) cases with profuse intestinal bleeding, the endoscopy showed diffuse spontaneous bleedings from colonic mucosa, with no local source of bleeding found.
 Biopsy samples from colonic mucosa were taken from 47 patients. Morphological abnormalities of only moderate or dense lymphoplasmocytic infiltration were detected in 29 (67.7%) patients, erosions in 8 (17%). In 2 (4.3%) cases, highly dense lymphoid infiltration with neutrophils, eosinophils and crypt abscesses was found, as typical for ulcerative colitis. In 2 (4.3%) patients, the lymphoid infiltration was associated with small venular and arteriolar clots, and in 5 (10.6%) patients there were no significant morphological abnormalities, except mild lymphoid infiltration.
 During the hospitalization period, 56.9% of the patients showed a decrease in stool frequency, improvement of clinical and laboratory signs of systemic inflammation and metabolic abnormalities, and partial restoration of their body weight. One patient with ulcerative colitis received adalimumab and achieved stable clinical and endoscopic remission. Complete recovery was noted in 27.8% of the cases within 4–8 weeks, among them in 1 patient who had had profuse intestinal bleedings. In 3 cases (4.2%), an emergency colectomy was performed due to severe pseudomembranous colitis. Two (2.8%) deaths were registered: one patient with newly diagnosed post-COVID severe ulcerative colitis died of pneumonia, and another patient died of severe multiorgan failure. In 6 (8.3%) cases, a moderate long-term (above 8 weeks) diarrhea with metabolic disorders, weight loss, but without systemic inflammation was noted.
 Conclusion: In patients with post-COVID intestinal lesions, the clinical symptoms are almost the identical and manifest with diarrhea of varying severity, systemic inflammation and metabolic disorders, whereas the endoscopic and morphological lesions are quite diverse. The severity of clinical symptoms often does not correspond to poorly expressed endoscopic and morphological signs. The variability and inconsistency of the clinical, endoscopic and morphological changes have not yet been systematized and do not allow for a clearly formulated diagnosis (except cases of pseudomembranous and ulcerative colitis). This makes it impossible to provide pathophysiologically-based treatments.

Phage transcriptional regulator X (PtrX)-mediated augmentation of toxin production and virulence in Clostridioides difficile strain R20291

Clostridioides difficile is a Gram-positive, anaerobic, and spore-forming bacterial member of the human gut microbiome. The primary virulence factors of C. difficile are toxin A and toxin B. These toxins damage the cell cytoskeleton and cause various diseases, from diarrhea to severe pseudomembranous colitis. Evidence suggests that bacteriophages can regulate the expression of the pathogenicity locus (PaLoc) genes of C. difficile. We previously demonstrated that the genome of the C. difficile RT027 strain NCKUH-21 contains a prophage-like DNA sequence, which was found to be markedly similar to that of the φCD38–2 phage. In the present study, we investigated the mechanisms underlying the φNCKUH-21-mediated regulation of the pathogenicity and the PaLoc genes expression in the lysogenized C. difficile strain R20291. The carriage of φNCKUH-21 in R20291 cells substantially enhanced toxin production, bacterial motility, biofilm formation, and spore germination in vitro. Subsequent mouse studies revealed that the lysogenized R20291 strain caused a more severe infection than the wild-type strain. We screened three φNCKUH-21 genes encoding DNA-binding proteins to check their effects on PaLoc genes expression. The overexpression of NCKUH-21_03890, annotated as a transcriptional regulator (phage transcriptional regulator X, PtrX), considerably enhanced toxin production, biofilm formation, and bacterial motility of R20291. Transcriptome analysis further confirmed that the overexpression of ptrX led to the upregulation of the expression of toxin genes, flagellar genes, and csrA. In the ptrX-overexpressing R20291 strain, PtrX influenced the expression of flagellar genes and the sigma factor gene sigD, possibly through an increased flagellar phase ON configuration ratio.

Nutritional support in the complex therapy of clostridial infection after surgery

This article presents the tactics of nutritional support in a patient with pseudomembranous colitis after repeated consecutive operations on the abdominal organs, which led to significant violations of the nutritional status. Competent, individually selected correction of protein-energy deficiency in patients with pseudomembranous colitis allows achieving an effective treatment result, avoiding severe complications such as perforation, toxic dilatation, and bleeding. The peculiarity of this clinical case is that a patient with perforation of Meckels diverticulum and abdominal abscess developed a complication secondary widespread peritonitis, phlegmon, which required repeated surgical interventions. Surgical treatment and massive antibiotic therapy led to the development of Clostridium difficile infection: during the treatment the patient developed multiple loose stools and C. difficile toxins A and B were detected. Severe pseudomembranous colitis was accompanied by protein-energy deficiency (hypoproteinemia, hypoalbuminemia), severe dehydration, hypokalemia, hyponatremia, and moderately severe anemia of complex genesis. When selecting nutritional support for patients with clostridial infection, it is important to take into account severe systemic inflammation, which affects the absorption and absorption of the intestinal wall, which in turn determines the route of introduction of nutrient substrates. In this case we needed to choose the right method for correcting the patients nutritional status.

Redistribution of the Novel Clostridioides difficile Spore Adherence Receptor E-Cadherin by TcdA and TcdB Increases Spore Binding to Adherens Junctions.

Clostridioides difficile causes antibiotic-associated diseases in humans, ranging from mild diarrhea to severe pseudomembranous colitis and death. A major clinical challenge is the prevention of disease recurrence, which affects nearly ~20 to 30% of the patients with a primary C. difficile infection (CDI). During CDI, C. difficile forms metabolically dormant spores that are essential for recurrence of CDI (R-CDI). In prior studies, we have shown that C. difficile spores interact with intestinal epithelial cells (IECs), which contribute to R-CDI. However, this interaction remains poorly understood. Here, we provide evidence that C. difficile spores interact with E-cadherin, contributing to spore adherence and internalization into IECs. C. difficile toxins TcdA and TcdB lead to adherens junctions opening and increase spore adherence to IECs. Confocal micrographs demonstrate that C. difficile spores associate with accessible E-cadherin; spore-E-cadherin association increases upon TcdA and TcdB intoxication. The presence of anti-E-cadherin antibodies decreased spore adherence and entry into IECs. By enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and immunogold labeling, we observed that E-cadherin binds to C. difficile spores, specifically to the hairlike projections of the spore, reducing spore adherence to IECs. Overall, these results expand our knowledge of how C. difficile spores bind to IECs by providing evidence that E-cadherin acts as a spore adherence receptor to IECs and by revealing how toxin-mediated damage affects spore interactions with IECs.

Clinical case of severe pseudomembranous colitis caused by pathogenic infection <i>Clostridium Difficile</i>

Objective. Literature review of pseudomembranous colitis caused by pathogenic Clostridium difficile infection and description of a clinical case of pseudomembranous colitis.
 Materials and methods. A clinical case of a patient with pseudomembranous colitis is presented.
 Results. In a patient with multiple injuries and grade II shock, whose condition required numerous surgical interventions and intensive antibiotic therapy, after the completion of antibiotic therapy there appeared signs of pseudomembranous colitis loose stools (up to 5 times a day), fever up to 39 C, signs of endogenous intoxication, A C. difficile toxin was found in faeces. Antibiotic-associated colitis was diagnosed; metronidazole 500 mg 3 times a day, activated charcoal, infusion therapy were prescribed on the 12th day, the therapy led to recovery. During the subsequent reconstructive operation, lincomycin 600 mg was administered by infusion for prophylactic purposes, after which, 6 hours later, the patient developed a clinical picture of severe pseudomembranous colitis. A laboratory study of faeces again revealed toxin A C. difficile. The recurrence of the disease required a long-term treatment in the gastroenterology department.
 Conclusions. Pseudomembranous colitis is certainly a complex pathology that is a serious hospital-acquired infection. Accurate diagnosis requires correct assessment of the patients condition through clinical and laboratory diagnostic methods, correct prescription of conservative treatment and choice of surgical intervention tactics.

Clostridioides difficile-Infection (CDI)

Clostridioides difficile is a Gram positive, spore-forming bacillus colonizing the lower gastrointestinal tract. Use of antibiotics, older age, and underlying diseases contribute to changes in the microbial flora of the gut, which may lead to the production of toxins that cause C. difficile infection (CDI), with symptoms ranging from mild to moderate diarrhea to severe diarrhea, pseudomembranous colitis, toxic megacolon and sepsis. CDI is difficult to treat and has a high risk of recurrence. The fecal-oral route is the predominant mode of C. difficile transmission. The highest CDI incidence rates are reported from developed countries, particularly the United States, but limited disease awareness and surveillance capacity may lead to underestimation of disease burden elsewhere. Treatment consists of stopping ongoing antibiotic treatment, specific anti-CDI antibiotics and fecal microbiota transplant (FMT). CDI recurrence can be prevented by an anti-toxin B monoclonal antibody, bezlotoxumab. Various hygiene measures should be applied but they are costly and of variable effect. A candidate vaccine directed at the C. difficile toxin failed in the past, possibly due to a change in the epitope through inactivation or to a suboptimal immunization schedule. Currently, only one vaccine candidate based on genetically and chemically detoxified toxins A and B is in phase III studies.

Severe pseudomembranous colitis in patients with previous coronavirus infection

To analyze treatment outcomes in patients with severe pseudomembranous colitis and previous coronavirus infection. We retrospectively analyzed treatment outcomes, clinical, laboratory and histological data in convalescents of COVID-19 who admitted to the department of coloproctology for moderate-to-severe pseudomembranous colitis confirmed by endoscopic examination between 2020 and 2021. There were 13 patients with moderate pseudomembranous colitis and 6 ones with severe pseudomembranous colitis. Mean period after recovery from coronavirus infection was 19 days. Endoscopy revealed whitish-yellow or gray raised plaques on colonic mucosa in all cases. Four patients with signs of peritonitis underwent emergency surgery. Three patients had perforation of caecum; one patient had perforation of sigmoid colon and widespread peritonitis. Two patients underwent urgent surgery for progressive toxic megacolon and ineffective therapy. Subtotal colectomy and ileostomy were performed in all cases. Histological examination revealed necrosis of not only superficial layer of colon mucosa typical for clostridial colitis, but also the entire thickness of mucosa, as well as submucosal and partially muscular layers in some cases. Mucosal crypt atrophy, fibrinoid effusion in muscular layer, diffuse polymorphonuclear cell infiltration and necrosis of muscular and submucosal nerve plexuses, as well as necrosis of vascular walls with deposition of hyaline-like structures characterize microcirculatory ischemic processes in the colon wall. Severe pseudomembranous colitis associated with COVID-19 may not be associated with clostridial infection. Further analysis of possible ischemic etiology and pathogenesis of gastrointestinal lesions in COVID-19 is needed for preventive and therapeutic measures.

Successful Experience of Fecal Transplantation in a Patient with Severe Pseudomembranous Colitis

Introduction . At the present time there is increase the number of patients diagnosed with pseudomembranous colitis due to Clostridiodes difficile, respectively it significantly increases the frequency of hospitalizations, the length of hospital stay and the cost of treatment. Approved drug methods for correcting a pathological condition are not always able to lead to recovery after the first use, repeated and prolonged courses of therapy are often required, especially with recurrent Clostridiodes difficile. An alternative way of treatment is fecal microbiota transplantation from a donor. Nowadays, fecal microbiota transplantation is included in national clinical guidelines in several countries in Europe, the USA and Australia. In Russia this method has not been registered, however, there are some publications about its successful application in gastrointestinal diseases, oncohematology, and some autoimmune diseases. Aim . To show the result of successful treatment of severe pseudomembranous colitis after a single fecal microbiota transplantation. Material and methods . Outpatient treatment of an acute respiratory infection with a broad-spectrum antibacterial drug caused the development of severe pseudomembranous colitis in a young patient. Standard courses of metronidazole and vancomycin were unsuccessful. Transplantation of fecal microbiota from a donor was performed via ileocolonoscopy. Results. A single fecal microbiota transplantation contributed to the patient’s complete recovery, short term rehabilitation and the absence of recurrence of Clostridiodes difficile within two years. Conclusions. Evidence-based medicine has shown the high efficiency of fecal microbiota transplantation. In Russia a legislative basis is needed for including fecal microbiota transplantation in clinical guidelines for the treatment of severe Clostridiodes difficile resistant to standard therapy .

Клиническое наблюдение псевдомембранозного колита, осложненного множественными перфорациями ободочной кишки

Objective: To present a clinical observation of a patient with pseudomembranous colitis (PMC) complicated with multiple colon perforations, and of post-surgery recovery. Key Points. Severe PMC can cause complications, such as toxic dilatation and perforation on colon, requiring emergency surgery. Clinical observation demonstrates the advisability of extended surgery for a patient with PMC complicated with perforations. Conclusion. PMC is a dangerous disease; a severe disease can cause colon perforation and require emergency surgery. Near-total colon excision in perforation in patients with PMC is justified and a most advisable type of surgery. Keywords: pseudomembranous colitis, multiple perforations, general peritonitis.

Prevalence and phylogenetic relationship of Clostridioides difficile strains in fresh poultry meat samples processed in different cutting plants

Clostridioides difficile is one of the most frequent causes of nosocomial infections in humans leading to (antibiotic-associated) diarrhea and severe pseudomembranous colitis. With an increasing frequency, C. difficile infections (CDI) are also observed independently of hospitalization and the age of the patients in an ambulant setting. One potential source of so-called community-acquired CDI is a zoonotic transmission to humans based on direct contact with animals or the consumption of food.To estimate the exposure of humans with C. difficile via food, we screened 364 different retail fresh poultry meat products purchased in Berlin and Brandenburg, Germany and further characterized the isolates. None of the 42 turkey or chicken meat samples without skin was contaminated. However, 51 (15.8%) of 322 tested fresh chicken meat samples with skin were C. difficile-positive. The vast majority (84.3%) of all isolates exhibited toxin genes tcdA and tcdB, whereas the binary toxin cdtA/B was absent. Most of the isolates (50/51) were susceptible to all six investigated antimicrobials. However, one non-toxigenic strain was multidrug resistant to the antimicrobials clindamycin and erythromycin. The isolates were mainly represented by PCR-ribotypes (RT) 001, RT002, RT005, and RT014, which were already associated with human CDI cases in Germany and were partially detected in poultry. The relatively high contamination rate of fresh retail chicken meat with skin purchased in Germany indicates chicken meat as a potential source of human infections. Moreover, we identified cutting plants with a higher rate of a C. difficile-contamination (21.4–32.8%). To compare the phylogenetic relationship of the isolated strains from certain cutting plants over several months in 2018 and 2019, we analyzed them using NGS followed by core genome MLST. Interestingly, highly related strains (0–3 alleles distance) of common clinical RT001 and RT002 isolates, as well as of the non-toxigenic RT205 isolates were detectable in same cutting plants over a period of three and 16 months, respectively.The continuous contamination with the same strain could be explained by the longterm persistence of this strain within the cutting plant (e.g., within the scalder), or with a recurring entry e.g. from the same fattening farm.

Impact of subinhibitory concentrations of metronidazole on proteome of Clostridioides difficile strains with different levels of susceptibility.

Clostridioides difficile is responsible for various intestinal symptoms from mild diarrhea to severe pseudomembranous colitis and is the primary cause of antibiotic-associated diarrhea in adults. Metronidazole was the first-line treatment for mild to moderate C. difficile infections for 30 years. However, clinical failure and recurrence rates of metronidazole is superior to oral vancomycin and metronidazole is now recommended only as an alternative to vancomycin or fidaxomicin, for an initial non-severe infection. The mechanisms of treatment failure and infection recurrence remain unclear. Given the poor fecal concentrations of metronidazole, the bacteria may be exposed to subinhibitory concentrations of metronidazole and develop adaptation strategy, which is likely to be the origin of an increase in treatment failures. In this study, a proteomic approach was used to analyze changes in the proteome of two strains with different levels of susceptibility to metronidazole in the presence of subinhibitory concentrations of this antibiotic. The two strains were grown to stationary phase: CD17-146, a clinical C. difficile isolate with reduced susceptibility to metronidazole, and VPI 10463, a metronidazole susceptible strain. Our study revealed that, whatever the strain, subinhibitory concentrations of metronidazole modified the amount of proteins involved in protein biosynthesis, glycolysis, and protection against stress induced by metronidazole, as well as in DNA repair. Several proteins involved in stress response are known to be synthesized under the control of Sigma factor B, which suggests a close link between Sigma factor B and metronidazole. Interestingly, impact of metronidazole on protein production for VPI 10463 strain differed from CD17-146 strain, for which the amount of two proteins involved in biofilm formation of CD17-146 were modified by metronidazole.

Clinical Case of a Patient with Small Bowel Obstruction and Multiple Diospirobesoaras of the Gastrointestinal Tract

AbstractSmall bowel obstruction (SBO) is 3-4% of all abdominal acute diseases. Small bowel obstruction due to bezoars is rare (2-4%), and is detected mainly in patients with predisposing risk factors: gastrointestinal motility disorders, psychiatric diseases, enzymatic insufficiency, previous bariatric surgery, diabetes mellitus and hypothyroidism complicated by gastroparesis. The leading role in the verification of small bowel obstruction in patients without surgical interventions on the abdominal organs should be given to computed tomography. According to the literature, the mortality from SBO due to bezoar may reach 30%. We present an unusual clinical case of recurrent small bowel obstruction with severe intestinal disease and septic shock induced by multiple phytobezoars and complicated with severe pseudomembranous colitis. Moreover, in our opinion, laparoscopic access can be used both for diagnostic and therapeutic purposes in patients with acute small bowel obstruction.

Microbiota in Clostridioides difficile-Associated Diarrhea: Comparison in Recurrent and Non-Recurrent Infections.

Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea, especially in hospitalized elderly patients, representing a global public health concern. Clinical presentations vary from mild diarrhea to severe pseudomembranous colitis that may progress to toxic megacolon or intestinal perforation. Antibiotic therapy is recognized as a risk factor and exacerbates dysbiosis of the intestinal microbiota, whose role in CDI is increasingly acknowledged. A clinically challenging complication is the development of recurrent disease (rCDI). In this study, using amplicon metagenomics, we compared the fecal microbiota of CDI and rCDI patients (sampled at initial and recurrent episode) and of non-infected controls. We also investigated whether CDI severity relates to specific microbiota compositions. rCDI patients showed a significantly decreased bacterial diversity as compared to controls (p < 0.01). The taxonomic composition presented significant shifts: both CDI and rCDI patients displayed significantly increased frequencies of Firmicutes, Peptostreptococcaceae, Clostridium XI, Clostridium XVIII, and Enterococcaceae. Porphyromonadaceae and, within it, Parabacteroides displayed opposite behaviors in CDI and rCDI, appearing discriminant between the two. Finally, the second episode of rCDI was characterized by significant shifts of unclassified Clostridiales, Escherichia/Shigella and Veillonella. No peculiar taxa composition correlated with the severity of infection, likely reflecting the role of host-related factors in determining severity.

A265 SERIAL FECAL MICROBIOTA TRANSPLANT PLUS FIDAXOMICIN IN THE TREATMENT OF SEVERE OR FULMINANT CLOSTRIDIOIDES DIFFICILE INFECTION

Abstract Background Severe and fulminant Clostridioides Difficile infection(CDI) is associated with increased mortality and morbidity. Current guidelines recommend high dose vancomycin with metronidazole for treatment. Surgery is a high risk for patients failing medical therapy partly due to multiple comorbidities. Emerging evidence suggests efficacy of sequential fecal microbiota transplantation(FMT) by colonoscopy combined with vancomycin in patients failing maximal medical therapy. Fidaxomicin is non-inferior to vancomycin in treating CDI; however, it has not been studied in severe/fulminant cases. It is not known if FMT by enema combined with fidaxomicin is efficacious and safe in this patient population. Aims This single center, prospective, open-label pilot study aimed to determine the efficacy and safety of combined sequential FMT by enema plus fidaxomicin in severe or fulminant CDI not responding to maximal medical therapy. Primary outcome was resolution of diarrhea 2 weeks following final FMT. Secondary outcomes were resolution of diarrhea 8 weeks following final FMT, safety of proposed treatment protocol and colectomy rate. Methods Consecutive patients with severe or fulminant CDI, who fulfilled study inclusion criteria were recruited. Sequential cycles of FMT, administered by enema daily over three days(720cc followed by 360cc and 180cc), plus fidaxomicin 200mg PO BID were given. Clinical symptoms and inflammatory markers were monitored during the study and subsequent cycles of FMT were administered when clinical or biochemical improvement plateaued. A final FMT was administered with CDI resolution. Results A total of three patients were enrolled between Jan 22 to Aug 8, 2019, shown in Table 1. One patient had fulminant CDI due to shock, and the others had severe CDI. All had severe pseudomembranous colitis seen on endoscopy at enrollment. Two of three patients reached both primary and secondary outcomes with 2 FMT cycles. The only patient who did not reach the primary was successfully managed with long term vancomycin suppression. This patient had failed multiple FMTs prior to enrollment. There were no adverse events noted and no colectomy was required during this study. Conclusions This pilot study is the first to demonstrate efficacy and safety of combined sequential FMT by enema and fidaxomicin in treating severe or fulminant CDI patients. An adequately powered study is required to validate these findings. Funding Agencies CIHRAlberta Health Services, University of Alberta Hospital Foundation

A Case of Severe Pseudomembranous Colitis with Septic Shock

偽膜性大腸炎は抗菌薬関連消化管病変の一つで，CD（Clostridium difficile）が起因菌となる事が多い．急速に増悪し敗血症性ショックを呈した１例を経験したので報告する．症例は79歳女性．他院で尿路感染症に対し抗菌薬治療を受けていた所，嘔吐を来し，ショック状態となり当科に紹介された．初診時意識不明瞭でSIRS，DIC状態であった．腹部CT検査で左半結腸に全周性の壁肥厚を認め，便中のCD toxin陰性であったが治療歴から偽膜性大腸炎による腹膜炎を強く疑い，同日緊急手術施行．左半結腸は壁肥厚・島状菲薄および黒色壊死像を認めたため切除し横行結腸に人工肛門を造設した．切除標本の培養検査でCD陽性，病理組織検査で偽膜性大腸炎と診断された．偽膜性大腸炎の重症例で急性腹症例，ショック例などでは手術を考慮すべきとされている．自験例も時期を逸することなく積極的な手術療法を行い良好な経過を得た．

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.

Sub-lethal doses of surotomycin and vancomycin have similar effects on Clostridium difficile virulence factor production in vitro.

Clostridium difficile is an anaerobic spore-forming bacterial pathogen that causes a spectrum of illness severity ranging from mild diarrhoea to severe life-threatening pseudomembranous colitis. C. difficile infection (CDI) is antibiotic-associated and primarily mediated by two exotoxins, Toxins A and B. We and others have shown that some antibiotics stimulate Toxin A and B production by C. difficile in a strain-specific manner. Still, the effects of newer anti-C. difficile antibiotics on this process and spore formation remain to be investigated. Surotomycin (formally CB-183,315) is a novel, minimally absorbed, narrow-spectrum antibiotic. We determined the effects of surotomycin on C. difficile growth, toxin production and sporulation in historical and BI/NAP1/027 epidemic strains of C. difficile.Results/Key findings. While antibiotic free controls showed toxin production during the stationary phase growth, all strains exposed to sub-inhibitory concentrations of surotomycin and vancomycin demonstrated increased TcdA and TcdB production during early (log phase) growth by all strains. However, this effect was not observed at 24 or 48 h post-treatment by any of the C. difficile strains exposed to either antibiotic. Additionally, all doses of surotomycin and vancomycin suppressed spore formation in all tested strains. In summary, these findings demonstrate that surotomycin and vancomycin have similar effects on exotoxin production and sporulation by C. difficile in vitro. Furthermore, since spores contribute to recurrent infection, the ability of surotomycin to suppress spore formation may explain its ability to disrupt the reinfection cycle in the clinical setting.

Antibiotic-associated diana, intelligent Clostridium difficiary

Objective: To study antibiotic-associated diarrhea due to Clostridium difficile. Materials and methods : a retrospective and prospective analysis of literature and studies on C. difficile antibiotic-associated diarrhea was conducted. Results Despite the concerted efforts to improve the prevention and treatment of C. difficile infection, this infection remains common and serious both in hospitals and among the population. In recent years, germ cell transplantation has emerged as a safe and effective strategy for treating relapsing infections. With further improvement, the microbial transplantation of feces is likely to become the standard of care for periodic infections. Despite the fact that antibiotic therapy and decontamination in health facilities remain important for infection control, effective probiotics and vaccination are likely to become important tools for preventing infection C. difficile in the future. By this time, C. difficile infection continues to be a common and very painful consequence of the use of antibiotics. Pathogenic C. difficile strains form two protein exotoxins, toxin A and toxin B, which cause damage to the intestinal mucosa and inflammation. The infection can be asymptomatic, cause mild diarrhea or cause severe pseudomembranous colitis. The first step is to stop the use of an antibiotic that causes diarrhea. If diarrhea and colitis are serious or persistent, then the drugs of choice are metronidazole and vancomycin. Clostridium difficile is an anaerobic gram-positive, spore-forming, toxin-producing bacilli that is transmitted to humans through the fecal-oral transmission mechanism. In the United States, C. difficile is the most frequently reported nosocomial pathogen in 2011, with 453,000 cases of C. difficile infection and 29,000 deaths associated with C. Difficile infection. Conclusions . To date, the incidence of C. difficle-infections has increased, due to the wide and often uncontrolled use of antibiotics. It should be noted that antibiotic-associated diarrheas due to C. difficile occupy one of the first places in the structure of morbidity and mortality among infectious diarrheas, representing a serious and antimicrobial problem of therapy in the conditions of the in-patient and among the population. CDI has become an increasingly common infection and has shown an increase in severity over the past few years.