Toxic Megacolon Research Articles

Clostridioides difficile surface layer protein triggered inflammasome activation is mediated by membrane lipid raft

Clostridioides difficile is the leading cause of nosocomial infectious diarrhea, with clinical symptoms ranging from mild diarrhea to pseudomembranous colitis and toxic megacolon. Despite the use of vancomycin and fidaxomicin as standard drugs for the treatment of C. difficileinfection (CDI), clinical relapse rates remain high. Therefore, new alternative therapeutics to treat CDI are urgently required. Surface layer proteins (SLPs) are the most abundant proteins in the C. difficile cell wall, suggesting that they might involve in immune recognition. Here, we found SLPs as well as C. difficile induced inflammasome activation. In addition, the cholesterol‐rich microdomains, lipid rafts, on the cell membrane are thought to be crucial for bacterial adhesion and signal transduction. We demonstrated that lipid rafts participated in C. difficile SLPs binding to the cell membrane. Furthermore, both binding ability and inflammasome activation induced by SLP were abrogated with membrane cholesterol depletion by methyl‐β‐cyclodextrin (MβCD). The coalescence of SLPs in the cholesterol‐rich microdomains was confirmed in C. difficile‐infected cells. Our results demonstrate that SLPs recruit the lipid rafts, which may be a key step for C. difficile colonization and inducing inflammasome activation.

Prospective validation of AIIMS index as a predictor of steroid failure in patients with acute severe ulcerative colitis.

Optimal outcomes in acute severe ulcerative colitis (ASUC) are related to time-bound management based upon early prediction of response to intravenous (IV) steroids. In an earlier study, we described the All India Institute of Medical Sciences (AIIMS) index (baseline Ulcerative Colitis Endoscopic Index of Severity [UCEIS] ≥ 7 and day 3 fecal calprotectin [FCP] > 1000μg/g) for predicting failure of IV steroids. The current study is designed to validate this index in a prospective cohort. IV steroid-naïve patients with ASUC, satisfying Truelove and Witts' criteria, hospitalized from August 2018 to July 2019 were included. Patients' assessment included baseline sigmoidoscopy, day 1 and 3 FCP, hemogram, biochemistry and day 3 C-reactive protein. All patients received IV steroids, and the primary outcome was steroid failure, defined as the need for colectomy or rescue therapy with cyclosporine (CYC)/infliximab (IFX) during admission. Of the 47 patients, eight were excluded (four received steroids outside, two were directly taken for surgery/infliximab therapy, one had toxic megacolon, and one had infectious colitis), and 39 patients were included (mean age: 36.1 ± 12.6years, male: 31%). Fifteen patients (38%) failed IV steroid and required rescue therapy (IFX: 9, CYC: 2, Colectomy: 3, IFX followed by colectomy: 1). On univariate analysis, UCEIS ≥ 7 at baseline (p = 0.006), day 1 FCP (p = 0.03), day 3 FCP > 1000μg/g (p = 0.001), Oxford criteria (p = 0.04) and AIIMS index (p < 0.001) were significantly different between steroid responders and steroid failures. On multivariate analysis, day 3 FCP > 1000μg/g (odds ratio (odds ratio (OR)= 6.4;(95% CI =2.2-196.1) and baseline UCEIS ≥ 7 (OR) = 10.1;(95% CI = 2.1-80.2) were independent predictors. The AIIMS index predicted steroid failure with a better specificity (100% vs. 83%, p = 0.04) and positive predictive value (100% vs. 64%, p = 0.03) than Oxford criteria. AIIMS index has been validated in 39 prospective ASUC patients as an effective early predictor of steroid failure (sensitivity = 53%, specificity = 100%).

The Classification and Surgical Treatments in Adult Hirschsprung's Disease: A Retrospective Study.

PurposeTo explore the treatments and short-term effects of different types of adult Hirschsprung’s disease.Methods89 patients treated in Shanghai Changhai Hospital were retrospectively analyzed. According to the patient’s medical history, clinical manifestations, auxiliary examination and postoperative pathological results, the patients were divided into adult congenital megacolon, adult idiopathic megacolon, ganglion cell deficiency (types I and II), toxic megacolon and iatrogenic megacolon, The Treatment methods and short-term prognosis of patients in each group were summarized.Results41 cases of Hirschsprung’s disease in adults and low anterior resection or pull-out low anterior resection was performed, and 35 patients with idiopathic Megacolon were treated with one-stage subtotal colon resection under the condition of adequate preoperative preparation. Some patients admitted for emergency intestinal obstruction received conservative treatment first or underwent elective surgery after colonoscopic decompression was improved; two patients with ganglion cell deficiency subtotal colectomy were performed to remove the dilated proximal bowel segment and the narrow distal bowel segment; three patients with toxic Hirschsprung’s disease underwent colostomy in mild cases, while subtotal colorectal resection was required in severe cases; Iatrogenic megacolon was diagnosed in eight cases and the optimum operation should be selected according to the specific conditions of patients.ConclusionAdult Hirschsprung’s diseases were divided into adult congenital hirschsprung’s disease, idiopathic Hirschsprung’s disease, ganglion cell deficiency, toxic hirschsprung’s disease, and iatrogenic Hirschsprung’s disease. Different types of surgical treatments for Hirschsprung’s disease in adults should be selected according to the specific diagnosis. All patients with adult Hirschsprung’s diseases have good short-term outcomes after surgical treatment.

"PREVENTIVE MEASURES FOR CLOSTRIDIOIDES DIFFICILE INFECTIONS IN HOSPITAL SETTINGS: A LITERATURE REVIEW OF RECOMMENDATIONS AND NOVEL TARGETED STRATEGIES"

"Introduction: Clostridioides difficile infections (CDIs) are one of the most frequent hospital- acquired infections. The microorganism is considered the leading cause of acute diarrheal syndrome after the use of antibiotics, in Romania. Objective: The main objective is to provide a comprehensive review summarizing existing evidence regarding how CDIs can be prevented. Methods: We screened PubMed, PubMed Central (PMC), ScienceDirect, and Google Scholar, clinical trials in different phases, and several national and international guidelines on the subject of prevention of C. difficile infections, using specific keywords. Results: We divided the recommendations into the following categories: good practice, strong, weak, and no recommendations, while novel strategies are detailed separately. The newly available treatment options have been analyzed as well as the ongoing efforts to obtain novel therapies, such as synthetic biologics that curb C. difficile colonization and proliferation, the association between ribaxamase (a poorly absorbable beta-lactamase) and parenteral broad-spectrum antibiotics, antisense molecules with potent anti-difficile activity or antibody-based therapeutics. Conclusions: At the time of submission, there is no globally accepted guideline in regard to the management of patients with Clostridioides difficile infections. Conventional strategies have lowered the incidence of CDIs but seem insufficient to eradicate hospital-acquired C. difficile infections. The challenge of CDIs has pushed researchers towards novel approaches, which may be the solution for many difficult-to-treat infections. Keywords: Clostridioides difficile, CDI, ribotype 027, post-antibiotic infection, pseudomembranous colitis, toxic megacolon"

Robotic pyelolithotomy in a solitary pelvic kidney complicated with fulminant Clostridium difficile: a case report

BackgroundRobotic-assisted surgeries have gradually become the standard of care for many procedures, especially in the field of urology. Despite the widespread use of robotic assistance in surgeries, data on its postoperative complications are extremely limited. We detail a rare presentation of fulminant Clostridium difficile colitis requiring surgical intervention in a patient with a solitary ectopic pelvic kidney who underwent a robotic-assisted pyelolithotomy. Highlights of the most recent management recommendations for C. difficile infection are also presented.Case presentationA 26-year-old Caucasian woman who underwent a robot-assisted pyelolithotomy of a pelvic kidney developed tachycardia, leukocytosis, and severe diarrhea 2 days following surgery. Because of her long history of antibiotic use, her severe symptoms were concerning for C. difficile colitis. This was confirmed by a C. difficile toxin test and a computed tomography scan. She was given recommended antibiotics, but her condition progressively deteriorated. The patient developed fulminant colitis and toxic megacolon, for which she underwent an exploratory laparotomy with subtotal abdominal colectomy and ileostomy creation on the twelfth day of her hospitalization. She fully recovered and was discharged 3 weeks after her subtotal colectomy.ConclusionAlthough robotic surgeries have been shown to have several advantages, risk of postsurgical complications remains. We present a rare case of fulminant C. difficile colitis that complicated a robotic-assisted pyelolithotomy. Active prevention, early detection, and optimization of management are essential to preventing unfavorable outcomes.

Clostridioides (Clostridium) difficile in children with diarrhoea in Vietnam

BackgroundClostridioides (Clostridium) difficile commonly causes hospital-acquired infection which can range from mild diarrhoea to life-threatening toxic megacolon and even death. Reports on C. difficile infection (CDI) in Vietnam are limited, so this study was designed to evaluate the prevalence, molecular epidemiology and antimicrobial susceptibility of C. difficile isolated from children with diarrhoea in Vietnam. Infants are often colonised with C. difficile and it was hypothesised that those colonising strains would represent strains of C. difficile circulating in the hospital/region at the time, however, this was not an attempt to determine if C. difficile was the cause of the diarrhoea. MethodsDiarrhoeal stool samples collected at two children's hospitals in northern Vietnam from October 1, 2020 to February 28, 2021 were transported to Perth, Western Australia, for culture of C. difficile and further investigations on isolates; PCR ribotyping, toxin gene profiling and antimicrobial susceptibility testing. ResultsFrom these hospitals, 370 diarrhoeal stool samples were collected, most from children aged 1–15 months (71.9%; 266/370). The overall prevalence of C. difficile in stool samples from children aged ≤16 years was 37.8% (140/370) and the highest prevalence was in the 2–12 months age group (52.9%; 74/140). In total, 151 isolates of C. difficile were recovered; the proportion of toxigenic isolates was 16.6% (25/151). Of the 25 toxigenic C. difficile isolates, the toxin gene profiles A+B+CDT− and A−B+CDT− comprised 72% and 28%, respectively. The four most prevalent C. difficile ribotypes (RTs) were QX 011 (25/151), RT 010 (25/151), QX 107 (12/151) and RT 012 (11/151). All isolates were susceptible to vancomycin, metronidazole and fidaxomicin, while there was significant resistance to clindamycin (90.1%), and some to moxifloxacin (6.6%) and rifaximin (3.3%). ConclusionThe prevalence of C. difficile in children with diarrhoea was high (37.8%) although the proportion of toxigenic strains was comparatively low. The clinical significance of any isolate needs to be determined.

Acute Responses to Infectious and Inflammatory Disorders of the Gastrointestinal System

Infectious and inflammatory disorders of the gastrointestinal system are life-threatening and occur frequently in hospitalized adults. Inflammatory and inflammation-related diseases of the gastrointestinal tract seen in the acutely and critically ill have numerous causes. In acute pancreatitis and toxic infections caused by the bacterium Clostridium difficile, where severe infections can develop, inflammation plays a causative and crucial role. Severe acute pancreatitis puts a patient at risk for infected necrosis, which can result in septicemia and shock. Similarly, patients treated with antibiotics are at risk for C difficile colitis, which can progress to toxic megacolon. These conditions require volume resuscitation and interventions supported by current evidence. Percutaneous or surgical interventions are often undertaken at a critical point in these illnesses. Patients who require surgery for these diagnoses present challenges for the interprofessional team. Inflammatory and infectious disorders often can lead to complications of systemic inflammatory response syndrome, sepsis, and multiorgan failure. New strategies are on the horizon to prevent the onset of and improve care for patients with severe acute pancreatitis, fulminant C difficile infection, and megacolon.

Cellular adaptation of Clostridioides difficile to high salinity encompasses a compatible solute-responsive change in cell morphology.

Infections by the pathogenic gut bacterium Clostridioides difficile cause severe diarrhoeas up to a toxic megacolon and are currently among the major causes of lethal bacterial infections. Successful bacterial propagation in the gut is strongly associated with the adaptation to changing nutrition-caused environmental conditions; e.g. environmental salt stresses. Concentrations of 350 mM NaCl, the prevailing salinity in the colon, led to significantly reduced growth of C. difficile. Metabolomics of salt-stressed bacteria revealed a major reduction of the central energy generation pathways, including the Stickland-fermentation reactions. No obvious synthesis of compatible solutes was observed up to 24 h of growth. The ensuing limited tolerance to high salinity and absence of compatible solute synthesis might result from an evolutionary adaptation to the exclusive life of C. difficile in the mammalian gut. Addition of the compatible solutes carnitine, glycine-betaine, γ-butyrobetaine, crotonobetaine, homobetaine, proline-betaine and dimethylsulfoniopropionate restored growth (choline and proline failed) under conditions of high salinity. A bioinformatically identified OpuF-type ABC-transporter imported most of the used compatible solutes. A long-term adaptation after 48 h included a shift of the Stickland fermentation-based energy metabolism from the utilization to the accumulation of l-proline and resulted in restored growth. Surprisingly, salt stress resulted in the formation of coccoid C. difficile cells instead of the typical rod-shaped cells, a process reverted by the addition of several compatible solutes. Hence, compatible solute import via OpuF is the major immediate adaptation strategy of C. difficile to high salinity-incurred cellular stress.

Glucosyltransferase-dependent and independent effects of Clostridioides difficile toxins during infection.

Clostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea and pseudomembranous colitis in the USA. In addition to these symptoms, patients with CDI can develop severe inflammation and tissue damage, resulting in life-threatening toxic megacolon. CDI is mediated by two large homologous protein toxins, TcdA and TcdB, that bind and hijack receptors to enter host cells where they use glucosyltransferase (GT) enzymes to inactivate Rho family GTPases. GT-dependent intoxication elicits cytopathic changes, cytokine production, and apoptosis. At higher concentrations TcdB induces GT-independent necrosis in cells and tissue by stimulating production of reactive oxygen species via recruitment of the NADPH oxidase complex. Although GT-independent necrosis has been observed in vitro, the relevance of this mechanism during CDI has remained an outstanding question in the field. In this study we generated novel C. difficile toxin mutants in the hypervirulent BI/NAP1/PCR-ribotype 027 R20291 strain to test the hypothesis that GT-independent epithelial damage occurs during CDI. Using the mouse model of CDI, we observed that epithelial damage occurs through a GT-independent process that does not involve immune cell influx. The GT-activity of either toxin was sufficient to cause severe edema and inflammation, yet GT activity of both toxins was necessary to produce severe watery diarrhea. These results demonstrate that both TcdA and TcdB contribute to disease pathogenesis when present. Further, while inactivating GT activity of C. difficile toxins may suppress diarrhea and deleterious GT-dependent immune responses, the potential of severe GT-independent epithelial damage merits consideration when developing toxin-based therapeutics against CDI.

Potential Drug Targets Identification Against Clostridioides Difficile (CD) and Characterization of Indispensable Proteins by a Subtractive Genomics Approach Followed by Virtual Screening

Background:Clostridioides difficile (CD) is an enteric multi-drug resistant pathogenic bacterium. CD-associated infections are the leading cause of nosocomial diarrhea that can further lead to pseudomembranous colitis, toxic mega-colon or sepsis with greater mortality and morbidity risks. CD infection possesses higher rates of recurrence due to its greater resistance to antibiotics. Considering its higher rates of recurrence, it has become a major burden on healthcare facilities. Therefore, there is a dire need to identify novel drug targets to combat antibiotic resistance of Clostridioides difficile.Objective:To identify and propose new and novel drug targets against the Clostridioides difficile.Methods:In the current study, a computational subtractive genomics approach was applied to obtain a set of potential drug targets that exist in the multi-drug resistant strain of Clostridioides difficile. Here, the uncharacterized proteins were studied as potential drug targets. The methodology involved several bioinformatics databases and tools. The druggable proteins sequences were retrieved based on non-homology with host proteome and essentiality for the survival of the pathogen. The uncharacterized proteins were functionally characterized using different computational tools, and sub-cellular localization was also predicted. The metabolic pathways were analyzed using the KEGG database. Eventually, the druggable proteome has been fetched using sequence similarity with the already available drug targets present in the DrugBank database. These druggable proteins were further explored for the structural details to identify drug candidates.Results :A priority list of potential drug targets was provided with the help of the applied method on the complete proteome set of the C. difficile. Moreover, the drug-like compounds have been screened against the potential drug targets to prioritize potential drug candidates. To facilitate the need for drug targets and therapies, the study proposed five potential protein drug targets, out of which three proposed drug targets were subjected to homology modeling to explore their structural and functional activitiesConclusion:In conclusion, we proposed three unique, unexplored drug targets against C. difficile. The structure-based methods were applied and resulted in a list of top-scoring compounds as potential inhibitors to proposed drug targets.

Clostridioides difficile toxin B gen amplification cycle threshold as a predictor of severity

Clostridioides dfficile infection (CDI) is the main cause of nosocomial diarrhea, generally associated with the use of antibiotics. This infection can cause uncomplicated diarrhea to pseudomembranous colitis or toxic megacolon. Recent studies have attempted to relate the threshold cycle (Ct) value of RT-PCR with mortality, as a fast, simple, objective and efficient method. To evaluate Ct as a predictor of poor outcome in patients with C. dfficile disease with/without clinical signs of severity. We carried out a retrospective study between January 2015 and December 2018, including all patients in the reference area of the Hospital Universitario de Canarias in Tenerife (396,483 inhabitants) in patients with clinical criteria of severity and patients without clinical severity criteria (according to the guide for the clinical practice of CDI of the Society of Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of North America (IDSA). A total of 202 CDI episodes were diagnosed. 77.7% (n = 157) presented clinical severity criteria. The presence of ulcerative colitis (p < 0.001), fever (p < 0.001), leukocytosis (p < 0.001), neutrophilia (p < 0.001), creatininemia (p = 0.005) were presented as risk factors for the development of severe CDI (S-CDI). Female sex, institutionalization, previous admission and death were described more frequently in the group with S-CDI, not finding significant differences. We found no differences with respect to the days of previous stay, or of post-CDI stay, although in the latter, the mean was higher in the case of S-CDI patients. No significant differences were found in terms of Ct in both groups; being only one point lower in patients with severity criteria (Ct = 26.1) than without severity criteria (Ct = 27.4) (p = 0.326). Conclusión: Based on the results of our study, it has not been possible to systematically implement the Ct value as a predictor of severity to the clinical report, and it is not possible to extrapolate this predictive variable from S-CDI and standardize the Ct value as a predictor of severity. Basándonos en los resultados de nuestro estudio, no ha sido posible la implementación sistemática del valor Ct como predictor de gravedad al informe clínico, no siendo posible extrapolar esta variable predictora de enfermedad por C difficile-G y estandarizar el valor Ct como factor predictor de gravedad.

Incidence, prevalence, pathogenesis, and manifestations of toxic megacolon

Toxic megacolon is an inflammatory condition that affects the colon, leading to nonobstructive dilatation and serious morbidity. It can be found as total and segmental. In the present literature review, we have discussed the epidemiology, pathogenesis, and manifestations of toxic megacolon based on relevant data from studies in the literature. Unfortunately, reports regarding the prevalence and incidence of toxic megacolon are scarce. Therefore, it is difficult to draw a suitable conclusion in this context, and further studies are encouraged. Nevertheless, infection with Clostridium difficile might be the commonest etiology, and estimates indicate that this is a significant risk factor for developing the condition. In addition, colonic motility is usually inhibited by the significant presence of certain inflammatory mediators. Furthermore, the clinical manifestations of toxic megacolon are not very specific, and the diagnosis can be made through adequate history taking, together with clinical and radiological manifestations. Finally, prompt management of the condition is essential to intervene against the development of serious complications.

A Randomized Study Comparison between Split Dosage and Non-Split Dosage PEG-Electrolyte Solution Preparation Methods for Elective Colonoscopy

Background: A two liters low volume polyethylene glycol (PEG) electrolyte solution preparation was proposed for improving patients’ tolerability with either split or non-split dosage cleansing method. Patient compliance, adverse experiences, and cleansing efficacy of each anatomical segment of the colon using both methods should be determined. Objective: To assess the cleansing efficacy of split dosage versus non-split dosage PEG-electrolyte solution for each anatomical segment of the colon according to the inverted Ottawa bowel preparation scale. Materials and Methods: The present study was a prospective, randomized, endoscopist-blinded study. Volunteers that underwent elective screening colonoscopy were eligible for recruitment into the present study. Patients having any contraindication for colonoscopy, or the use of PEG-electrolyte solution such as bowel obstruction, intestinal perforation, or toxic megacolon were excluded. Cleansing efficacy was evaluated by the inverted Ottawa bowel preparation scale for each anatomical segment of the colon. Medical adherence and compliance were evaluated. Participants were asked to rate their satisfaction and inform the presence of any adverse experiences related to the bowel preparation method. Results: Ninety-four volunteers were randomly assigned to two groups. Of these, 46 received the split dosage cleansing method and 48 received the non-split dosages cleansing method. Overall compliance was approximately 94%, comparable for both preparation methods. Average age was 61.5 years for non-split dosage and 60.4 for split dosage group. Satisfaction score in the non-split dosage group was 8.46, which was not significantly different from 8.56 of the split dosage group (p=0.934). Split dosage PEG-electrolyte solution provided comparable degree of cleansing as standard non-split dosages preparation for transverse, descending, sigmoid, and rectum. However, split dosage provided significantly superior cleansing results over the non-split dosages method for ascending colon at good or excellent with 84.7% versus 47.9% (p&lt;0.01), and caecum at good or excellent for 76.1% versus 41.7% (p&lt;0.01) based on the inverted Ottawa bowel preparation scale. Conclusion: Split dosage PEG-electrolyte solution method provided significantly superior cleansing results over the non-split dosages method for right-side colon with comparable satisfaction score and rate of adverse events. Keywords: Bowel preparation; Split dosage cleansing; Quality of bowel preparation

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.

Toksični megakolon posle iracionalne primene antibiotika u lečenju trudnice sa Covid-om 19 - prikaz slučaja

Introduction: Optimal management of toxic megacolon as a consequence of Cl. difficile colitis is still matter of controversy, as well as timing of available therapeutic modalities. In this article we report a case of severe C. difficile colitis associated with toxic megacolon in a pregnant patient with Covid 19, who was successfully treated conservatively. Case Report: A 33-years old pregnant woman contracted SARS-CoV-2 in the 32nd week of pregnancy. She was admitted to regional hospital and treated extensively by wide-spectrum antibiotics. After the delivery she developed severe form of Cl. difficile colitis with toxic megacolon. In spite of severe clinical picture, the patient was treated conservatively, with high initial oral doses of vancomycin, with subsequent tapering. The outcome of the treatment was complete recovery and colonic functions were regained completely. Conclusion: In conclusion, our case shows that in younger patients, who were fit before occurrence of Cl. difficile colitis and toxic megacolon, conservative therapy should be tried as long as possible before turning to colectomy, since chances for cure without surgery are considerable.

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

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.

Incidence and Outcomes Associated With Clostridioides difficile Infection in Solid Organ Transplant Recipients

Little is known about the incidence and outcomes of Clostridioides difficile infection (CDI) in solid organ transplant (SOT) recipients. To estimate the CDI incidence and outcomes in SOT recipients. A population-based cohort study was conducted using administrative health care data for all Ontario, Canada, residents who received organ allografts from April 1, 2003, to December 31, 2017; March 31, 2020, was the end of the study period. The primary outcome was hospital admission with CDI diagnosis. The secondary outcomes included all-cause death, intensive care unit admission, acute kidney injury requiring dialysis, and fulminant CDI comprising any of the following: toxic megacolon, ileus, perforation, or colectomy. The association between short- vs long-term mortality (ie, death occurring within or after 90 days post-CDI) and the following variables was evaluated: age, sex, Deyo-Charlson Comorbidity Index, SOT type, early- vs late-onset CDI, fulminant CDI, intensive care unit admission, and acute kidney injury requiring acute dialysis. Overall, 10 724 SOT recipients (6901 [64.4%] men; median age, 54 [IQR, 44-62] years) were eligible. Kidney transplant was the most common SOT type (6453 [60.2%]). The median follow-up time was 5.0 (IQR, 2.3-8.8) years, resulting in 61 987 person-years of follow-up. A total of 726 patients (6.8%) were hospitalized with CDI. The 1-year CDI incidence significantly increased in annual cohorts (ie, from 23.1; 95% CI, 12.8-41.8 per 1000 person-years in 2004 to 46.7; 95% CI, 35.0-62.3 per 1000 person-years in 2017; P = .001). Clostridioides difficile was associated with a 16.8% rate (n = 122) of 90-day mortality. In patients who underwent kidney transplant, CDI was typically late-onset (median interval, 2.2; IQR, 0.4-6.0 years) compared with recipients of other organs. Acute kidney injury requiring dialysis was significantly associated with short-term (adjusted odds ratio [aOR], 1.86; 95% CI, 1.07-3.26) and long-term (adjusted hazard ratio [aHR], 1.89; 95% CI, 1.29-2.78) mortality, and late-onset CDI was also significantly associated with a greater risk of short-term (aOR, 4.26; 95% CI, 2.51-7.22) and long-term (aHR, 2.49; 95% CI, 1.78-3.49) mortality. In this study, increasing CDI trends in annual cohorts of SOT recipients were observed. Posttransplant CDI was associated with mortality, and late-onset CDI was associated with a greater risk of death than early-onset CDI. These findings suggest that preventive strategies should not be limited to the initial months following transplantation. Comprehensive therapeutic approaches targeting acute kidney injury risk factors in SOT recipients may reduce short- and long-term post-CDI mortality.

Etiological analysis and surgical method selection of adult megacolon

Adult megacolon is a rare disease with heterogeneneous etiology. The treatment schemes of megacolon caused by different causes are also different, but surgery is the final and the most effective method. Due to the lack of early understanding of the disease, many patients have not been clearly diagnosed as adult megacolon and have not been properly treated. This article classifies adult megacolon according to the etiology and summarizes its surgical options. For adult Hirschsprung's disease, modified Duhamel, the Jinling procedure, low anterior resection, or pull-through low anterior resection can be used. For patients with idiopathic megacolon, one-stage subtotal colorectal resection can be selected with adequate preoperative preparations. Some patients admitted to the hospital with emergency intestinal obstruction can be treated with conservative treatment or decompression under colonoscopy followed by selective surgery. For patients with aganglionosis, the procedure is subtotal colorectal resection, the same as that of idiopathic megacolon. The procedure is to remove both the dilated proximal intestine and the stenotic distal intestine, then an ileorectal anastomosis or ascending colon rectal anastomosis is performed. For toxic megacolon, colostomy can be done for mild cases, and for severe infections, subtotal colorectal resection is required. Latrogenic megacolon is mostly caused by segmental stenosis or lack of peristalsis, resulting in chronic dilatation of the proximal end and the formation of megacolon. It is necessary to choose a reasonable surgical procedure according to the specific conditions of the patient. The first choice for the treatment of acute colonic pseudo-obstruction syndrome is decompression under colonoscopy. For those with the secondary changes in the intestine, ostomy is still the most effective surgical procedure, but should be performed with caution.

Antibiotic Resistance in Clostridium Difficile: A Rapidly Evolving Threat

The bacteria, Clostridium difficile the main pathogen associated with nosocomial infections is a gram positive, anaerobic and forms spores. The host and pathogen reaction results in a wide array of manifestation of the disease which ranges at one end as asymptomatic carriage to the other end as severe; toxic megacolon and thus making the treatment with antibiotic a challenge. To add upon the Clostridium difficile shows antibiotic resistance making its eradication almost impossible. This antibiotic resistance of Clostridium difficile has made it a global challenge over the decades, making it impossible for us to come to a conventional antibiotic to treat infections by Clostridium difficile. Several new strains of Clostridium difficile have emerged following the unscrupulous use of antimicrobial agents and subsequent transfer of resistance-causing genes between virulent strains the subsequent generations. The resistance to antibiotics is still rampant and not in control, rather it is on rise as the bacteria has greater access to new host due to its mobility and very infectious nature. With the use of extended antimicrobial therapy, an acute danger of creating and spreading new resistant and multi-drug resistant strains always looms. Clostridium difficile, during its life cycle, produces spores, which give the organism the capacity to resist extremes of change in the environment. In a country such as India, with a high population density and thus forming a high potential platform for the spread of multidrug-resistant strains of Clostridium difficile isusually addressed. An understanding of the emergence of antibiotic resistance in Clostridium difficile, the mechanisms by which the Clostridium difficile acquires it and sensitivity to antibiotics becomes very important. Therefore, we present a review of the antibiotic resistance seen in Clostridium difficile. RT027 has emerged as the most virulent strain all the strain of Clostridium difficile. Drug resistance is via multiple pathways, including erm, cfr, tet, and rpo B genes, as well as Gyr A and Gyr B. Of these, tet is transferable to non-resistant strains. Thus, indiscriminate use of antibiotics has created multiple antibiotic resistant strains of Clostridium difficile. Judicious and planned antibiotic treatment is advisable.