Clostridium difficile Infections in an Emergency Surgical Unit from North-East Romania.

Background and Objectives: Colitis with Clostridium difficile is an important health problem that occurs with an intensity that varies between mild and severe. Surgical interventions are required only in fulminant forms. There is little evidence regarding the best surgical intervention in these cases. Materials and Methods: Patients with C. difficile infection were identified from the two surgery clinics from the 'Saint Spiridon' Emergency Hospital Iași, Romania. Data regarding the presentation, indication for surgery, antibiotic therapy, type of toxins, and post-operative outcomes were collected over a 3-year period. Results: From a total of 12,432 patients admitted for emergency or elective surgery, 140 (1.12%) were diagnosed with C. difficile infection. The mortality rate was 14% (20 cases). Non-survivors had higher rates of lower-limb amputations, bowel resections, hepatectomy, and splenectomy. Additional surgery was necessary in 2.8% of cases because of the complications of C. difficile colitis. In three cases, terminal colostomy was performed and as well as one case with subtotal colectomy with ileostomy. All patients who required the second surgery died within the 30-day mortality period. Conclusions: In our prospective study, the incidence was increased both in cases of patients with interventions on the colon and in those requiring limb amputations. Surgical interventions are rarely required in patients with C. difficile colitis.

Case of Pseudomembranous Colitis Caused by a Clostridioides difficile Infection Concomitant with Cytomegalovirus colitis Mimicking Ischemic Colitis.

A Clostridioides difficile infection (CDI) is one of the major nosocomial diarrheal diseases. Pseudomembranous colitis (PMC) is a characteristic endoscopic finding of CDI, manifested by white or yellowish plaque covering the colonic mucosa. Ischemic colitis is inflammation of the colon manifested by mucosal denudation and friability. Ischemic colitis is rarely associated with CDI. The treatment response might be delayed when CDI is complicated with other diseases that cause diarrhea. Thus far, reports of CDI concomitant with Cytomegalovirus (CMV) colitis are rare. This paper reports a case of PMC and ischemic colitis associated with CDI and CMV infection. After two weeks of oral vancomycin and intravenous metronidazole, the patient's diarrhea was not improved. Follow-up sigmoidoscopy was performed, and a CMV infection was identified at areas of broad ulceration where ischemic colitis occurred. Finally, the patient was cured with ganciclovir. Follow-up sigmoidoscopy showed an improvement in ischemic colitis.

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.

Increased clostridium difficile infection in the era of preoperative chemotherapy for pancreatic cancer.

BACKGROUND: In recent trend of preoperative chemotherapy, postoperative clostridium difficile infection (CDI) might be increasing in pancreatic ductal adenocarcinoma (PDAC) patients. This study aimed to elucidate the inducement of postoperative CDI in the new era of preoperative chemotherapy. METHODS: Eligible patients were those who received pancreaticoduodenectomy for PDAC. Patients were classified into two groups according to the presence or absence of postoperative CDI, and the independently associated factors for postoperative CDI were investigated. Additionally, eligible patients were classified using the identified associated factors, and the duration of preoperative antimicrobial administration and incidence of CDI were compared between the groups. RESULTS: Two hundred PDAC patients were eligible for this study, and postoperative CDI was detected in 15 (7.5%) patients. Multivariate analysis revealed that preoperative biliary tract infection (BTI) and chemotherapy (Chemo) were independently associated with postoperative CDI (OR, 4.05; 95% CI, 1.25-13.1; p = 0.0200 and OR, 3.64; 95% CI, 1.14-11.6; p = 0.0209, respectively). The patients were classified into four groups according to the presence or absence of preoperative BTI and Chemo (BTI-/Chemo-, BTI-/Chemo+, BTI+/Chemo- and BTI+/Chemo + group). The median durations of preoperative antimicrobial administration were 0, 2, 8 and 15 days in each group, respectively. Postoperative CDI was detected in 3.7%, 10.0%, 10.5% and 31.3% in each group, respectively, and patients in BTI+/Chemo + group suffered CDI more frequently compared to those in BTI-/Chemo-group (p = 0.00778). CONCLUSIONS: Preoperative BTI and chemotherapy might induce postoperative CDI for PDAC patients.

Risk factors of surgical mortality in patients with Clostridium difficile colitis. A novel scoring system.

BACKGROUND: The purpose of the study is to identify the risk factors of mortality and develop a risk scoring system in patients who underwent colectomy due to Clostridium difficile colitis (CD-C). METHODS: Patient information was extracted using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) data from 2012 to 2016. All adult patients who underwent colectomy for CD-C were included in the study. The data were split into training and testing data sets. A multiple logistic regression model was developed by backward deletion methods for risk assessment. To test the performance of the prediction model for 30-day mortality, a receiver operating characteristic (ROC) curve was generated and an area under the curve (AUC) was created. RESULTS: The training data set consisted of 434 (80%) patients, and the testing data set consisted of 91 (20%) patients. The overall mortality was 35%. No significant differences were found between the training and testing data sets for patient characteristics, comorbidities and mortality. The final model of the logistic regression model revealed a highly significant 30-day mortality for an age of ≥ 75 years old, ventilator dependency, Septic shock prior to surgery and a history of steroid use. The AUC value was 0.745 (95% CI 0.660-0.826). The risk of mortality scores range from 0 to 37. The highest score of 37 was related to an 83.9% predicted mortality. CONCLUSION: Older age, septic shock, ventilator dependency requiring supportive care and a history of chronic steroid use were highly associated with mortality. A nomogram showing the scores and their relationship to mortality may provide guidance to point of care physicians for deciding the goal of care. LEVEL OF EVIDENCE: Level of evidence: IV.

Reactive arthritis: an unusual presentation of acute Clostridioides difficile colitis.

A 20-year-old Caucasian man with a history of psoriasis presented to the emergency department due to a 2-week history of severe polyarthralgia and a 3-week history of non-bloody diarrhoea. The initial workup 2 days prior in an urgent care clinic returned negative for all enteric pathogens including Clostridioides difficile nucleic acid amplification test. Investigations revealed colitis on CT and pseudomembranous colitis on colonoscopy. The aspirate returned positive for C. difficile toxin. Tissue biopsies of the ascending, transverse, sigmoid colon and rectum were negative for chronicity to suggest inflammatory bowel disease with extraintestinal manifestation as the aetiology of polyarthralgia, which had been the most likely differential diagnosis until that point. The biopsy confirmed the diagnosis of reactive arthritis in the setting of C. difficile colitis. The patient improved on treatment with naproxen and was referred to rheumatology where he was found to be HLA-B27 positive.

Long-term Safety of Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.

BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection (CDI), with emerging data on intermediate and long-term safety. METHODS: A prospective survey-based study was conducted (September 2012-June 2018) in patients undergoing FMT for recurrent CDI. Data on demographics and comorbidities were abstracted from medical records. Patients were contacted at 1 week, 1 month, 6 months, 1 year (short-term), and ≥2 years post-FMT (long-term). Symptoms and new medical diagnoses were recorded at each time point. Data were weighted to account for survey nonresponse bias. Multivariate logistic regression models for adverse events were built using age (per 10-year increment), sex, time of survey, and comorbidities. P < .05 was considered statistically significant. RESULTS: Overall, 609 patients underwent FMT; median age was 56 years (range, 18-94), 64.8% were women, 22.8% had inflammatory bowel disease (IBD). At short-term follow-up (n = 609), >60% of patients had diarrhea and 19%-33% had constipation. At 1 year, 9.5% reported additional CDI episodes. On multivariable analysis, patients with IBD, dialysis-dependent kidney disease, and multiple FMTs had higher risk of diarrhea; risk of constipation was higher in women and lower in IBD (all P < .05). For long-term follow-up (n = 447), median time of follow-up was 3.7 years (range, 2.0-6.8). Overall, 73 new diagnoses were reported: 13% gastrointestinal, 10% weight gain, 11.8% new infections (all deemed unrelated to FMT). Median time to infections was 29 months (range, 0-73) post-FMT. CONCLUSION: FMT appears safe with low risk of transmission of infections. Several new diagnoses were reported, which should be explored in future studies.

Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis - An international cohort study.

BACKGROUND: Acid suppressing drugs (ASD) are generally used in acute pancreatitis (AP); however, large cohorts are not available to understand their efficiency and safety. Therefore, our aims were to evaluate the association between the administration of ASDs, the outcome of AP, the frequency of gastrointestinal (GI) bleeding and GI infection in patients with AP. METHODS: We initiated an international survey and performed retrospective data analysis on AP patients hospitalized between January 2013 and December 2018. RESULTS: Data of 17,422 adult patients with AP were collected from 59 centers of 23 countries. We found that 23.3% of patients received ASDs before and 86.6% during the course of AP. ASDs were prescribed to 57.6% of patients at discharge. ASD administration was associated with more severe AP and higher mortality. GI bleeding was reported in 4.7% of patients, and it was associated with pancreatitis severity, mortality and ASD therapy. Stool culture test was performed in 6.3% of the patients with 28.4% positive results. Clostridium difficile was the cause of GI infection in 60.5% of cases. Among the patients with GI infections, 28.9% received ASDs, whereas 24.1% were without any acid suppression treatment. GI infection was associated with more severe pancreatitis and higher mortality. CONCLUSIONS: Although ASD therapy is widely used, it is unlikely to have beneficial effects either on the outcome of AP or on the prevention of GI bleeding during AP. Therefore, ASD therapy should be substantially decreased in the therapeutic management of AP.

Successful Treatment of Pseudomembranous Colitis with Fecal Microbiota Transplantation - A Case Study on A Patient Rescued by Extracorporeal Cardiopulmonary Resuscitation After Cardiac Arrest.

BACKGROUND Pseudomembranous colitis (PMC) is an opportunistic, nosocomial infection caused by Clostridium difficile. CASE REPORT Here we described a patient who developed PMC during her recovery from cardiac arrest. A 16-year-old female high school student experienced sudden cardiac arrest. Spontaneous circulation was not returned by standard cardiopulmonary resuscitation. After her admission to the emergency unit, her cardiac function and neurologic function were finally resumed by extracorporeal cardiopulmonary resuscitation (ECPR); however, after 14 days, her recovery was complicated with excessive diarrhea and shock. Colonoscopy confirmed the diagnosis of PMC. Metronidazole and vancomycin were immediately administered; however, the treatment did not result in any improvement. Fecal microbiota transplantation was then performed, and after 4 transplantations, her diarrhea was significantly ameliorated. After hospital stay for 135 days, the patient was finally discharged with grade II brain function. She later recovered self-care ability in follow-up. CONCLUSIONS The patient suffered from a long-term gastrointestinal ischemia-hypoxia resulting from cardiac arrest. The use of broad-spectrum antibiotics in the later treatment led to refractory PMC, which was successfully managed by multiple fecal microbiota transplantation.

The Clinical Drug Ebselen Attenuates Inflammation and Promotes Microbiome Recovery in Mice after Antibiotic Treatment for CDI.

Clostridium difficile infection (CDI) is an enteric bacterial disease that is increasing in prevalence worldwide. C. difficile capitalizes on gut inflammation and microbiome dysbiosis to establish infection, with symptoms ranging from watery diarrhea to toxic megacolon. We reported that the safe-in-human clinical drug ebselen (ClinicalTrials.gov: NCT03013400, NCT01452607, NCT00762671, and NCT02603081) has biochemical, cell-based, and in vivo efficacy against the toxins of C. difficile. Here, we show that ebselen treatment reduces recurrence rates and decreases colitis in a hamster model of relapsing CDI. Furthermore, ebselen treatment does not alter microbiome diversity and promotes recovery back to that of healthy controls after antibiotic-induced dysbiosis in healthy and C. difficile-infected mice. This increased microbiome recovery upon ebselen treatment correlates with a decrease in host-derived inflammatory markers, suggesting that the anti-inflammatory properties of ebselen, combined with its anti-toxin function, help to mitigate the major clinical challenges of CDI, including recurrence, microbial dysbiosis, and colitis.

Clostridium difficile colitis in patients undergoing surgery for hip fractures: an analysis of 17,474 patients.

BACKGROUND: We compiled evidence from a large national surgical database to identify the incidence, risk factors and postoperative impact of Clostridium difficile infection (CDI) in patients undergoing hip fracture repair. METHODS: We identified 17,474 patients who underwent hip fracture repairs in 2015 using the ACS-NSQIP database. Interventions studied were open reduction/Internal fixation, total hip arthroplasty or hemiarthroplasty being performed for traumatic hip fractures. Outcomes studied were incidence, preoperative and postoperative risk factors for occurrence of CDI were studied using descriptive and statistical analysis. RESULTS: A total of 92 patients (0.53%) developed CDI within 30 days of the operation. Following adjustment using multi-variate logistic regression, preoperative and hospital-associated factors associated with development of CDI were smoking (OR 1.75 [95% CI 1.03-2.99]), hypertension (OR 1.70 [95% CI 1.01-2.85]), hyponatraemia (OR 1.65 [95% CI 1.04-2.63]), prior systemic inflammatory response syndrome (SIRS) (OR 2.18 [95% CI 1.32-3.59]) and a length of stay >7 days (OR 1.98 [95% CI 1.11-3.53]. Postoperative factors associated with occurrence of CDI were occurrence of a deep surgical site infection (SSI) (OR 5.89 [95% CI 1.31-26.6]), a stay in the hospital >30 days (OR 6.56 [95% CI 2.56-16.9]) and unplanned reoperations (OR 2.78 [95% CI 1.29-5.99]). CONCLUSION: As we move toward an era of bundled-payment models, identification of risk factors associated with the occurrence of postoperative complications, such as CDI, will help curb excess healthcare utilisation and costs associated with the management of this complication.

Acute oxalate nephropathy associated with C lostridium difficile infection.

Acute oxalate nephropathy has been associated with chronic diarrheal illness and only one case has been reported due to acute diarrhea secondary to Clostridium difficile colitis. To the best of our knowledge, this is the second case report of acute oxalate nephropathy due to C . difficile colitis. A 75-year-old man with a medical history of hypertension, type 2 diabetes mellitus, chronic kidney disease stage IV, recent C . difficile colitis was admitted for acute kidney injury with a creatinine (Cr) of 8.54 mg/dL (baseline Cr, 2.3-2.6 mg/dL). His urinalysis did not show any eosinophils, casts or crystals. Antinuclear antibody, antineutrophil cytoplasmic antibody, complement levels (C3 and C4) and hepatitis screen were negative; a renal ultrasound visualized no hydronephrosis. A kidney biopsy showed widespread tubular oxalate crystal deposition suggestive of hyperoxaluria as the cause of acute kidney injury. In conclusion, an acute diarrheal illness like C . difficile colitis can cause acute oxalate nephropathy.

Development and validation of a clinical risk calculator for mortality after colectomy for fulminant Clostridium difficile colitis.

BACKGROUND: Clostridium difficile colitis is an increasingly important cause of morbidity and mortality. Fulminant C. difficile colitis (FCDC) is a severe form of the colitis driven by a significant systemic inflammatory response, and managed with a total abdominal colectomy. Despite surgery, postoperative mortality rates remain high. The aim of this study was to develop a bedside calculator to predict the risk of 30-day postoperative mortality for patients with FCDC. METHODS: After institutional review board approval, the American College of Surgeons National Surgical Quality Improvement Program database (2005-2015) was used to include adult patients who underwent emergency surgery for FCDC. A priori preoperative predictors of mortality were selected from the literature: age, immunosuppression, preoperative shock, intubation, and laboratory values. The predictive accuracy of different logistic regression models was measured by calculating the area under the receiver-operating characteristic curve. A cohort of 124 patients from Québec was used to validate the developed mortality calculator. RESULTS: A total of 557 patients met the inclusion criteria, and the overall mortality was 44%. After developing the calculator, no statistically significant differences were found in comparison with the American College of Surgeons National Surgical Quality Improvement Program probability of mortality available in the database (area under the receiver operating curve, 75.61 vs. 75.14; p = 0.79). External validation with the cohort of patients from Quebec showed an area under the curve of 74.0% (95% confidence interval, 65.0-82.9). CONCLUSION: A clinically applicable calculator using preoperative variables to predict postoperative mortality for patients with FCDC was developed and externally validated. This calculator may help guide preoperative decision making. LEVEL OF EVIDENCE: Prognostic and epidemiological study, level III.

Liver infarction in a patient with Clostridium Difficile colitis. A possible connection?

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Colitis pseudomembranosa: a propósito de un caso / Pseudomembranosa colitis: apropos of a case

Fundamento: la colitis pseudomembranosa es una enfermedad causada por el clostridium difficile en los últimos tiempos ha llamado la atención de la comunidad médica, por aumento en la incidencia en las instituciones de salud, así como, en la comunidad, motivado por el consumo frecuente y a veces no ordenado de antimicrobianos. Objetivo:describir un caso de un paciente con diagnóstico postmorten de colitis pseudomembranosa. Caso clínico: paciente masculino de 71 años con antecedentes de enfermedad pulmonar obstructiva crónica y válvula protésica mitral, con esquemas de tratamientos antimicrobianos profilácticos cada mes para evitar infecciones respiratorias, el cual ingresó por presentar deposiciones diarreicas de escasa cantidad pero frecuentes con abundante sangre y moco acompañado de fiebre y dolor abdominal, con una evolución intrahospitalaria tórpida hasta su fallecimiento, el diagnóstico en la necropsia realizada arrojó una colitis pseudomembranosa. Conclusiones: la colitis pseudomembranosa producida por el clostridium difficile es una enfermedad que hay que tener presente en los diagnósticos de paciente hospitalizados los cuales se encuentran con tratamiento antimicrobianos o que procedan de la comunidad donde se les prescribió con este tipo de fármacos(AU)

Background: pseudomembranous colitis is a disease caused by Clostridium difficile in recent times has attracted the attention of the medical community, due to an increase in the incidence in health institutions, as well as in the community, motivated by the more frequent use and sometimes not ordered antimicrobials.Objective: to describe a case of a patient with a postmortem diagnosis of pseudomembranous colitis. Clinical case: a 71-year-old male patient with a history of chronic obstructive pulmonary disease and mitral prosthetic valve to receive from several months prophylactic antimicrobial cycles every month to avoid respiratory infections, who is admitted due to scarce diarrheic stools, but frequent with abundant blood and mucus accompanied by fever and abdominal pain, with an intra-hospital torpid evolution until his death, performing the diagnosis of pseudomembranous colitis in the necropsy study. Conclusions: the pseudomembranous colitis produced by Clostridium difficile is a disease that has to be kept in mind in the diagnoses of hospitalized patients who are under antimicrobial treatment or who come from the community where they were prescribed with this type of drugs(AU)