Clostridium Difficile-associated Colitis Research Articles

Evaluation of anti-infective-related Clostridium difficile-associated colitis using the Japanese Adverse Drug Event Report database.

Clostridium difficile-associated colitis (CDAC) may cause gastrointestinal illness, ranging in severity from mild diarrhea to fulminant colitis and even mortality. The purpose of this study was to evaluate anti-infective-related CDAC profiles using the Japanese Adverse Drug Event Report (JADER) database.Methods: We selected case reports of adverse events of CDAC as specified in the Medical Dictionary for Regulatory Activities. The association between the number of administered anti-infectives and aging was evaluated using reporting odds ratio (ROR) and adjusted for covariates using multiple-logistic regression. We also evaluated anti-infective-related CDAC-onset profiles using Weibull shape parameter.Results: The JADER database contained 534 688 reports from April 2004 to June 2018. There were 1222 anti-infective related CDAC events. The top five anti-infectives were as follows: third-generation cephalosporins (Anatomical Therapeutic Chemical (ATC) code: J01DD, 313 cases), fluoroquinolones (ATC code: J01MA, 201 cases), macrolides (ATC code: J01FA, 146 cases), carbapenems (ATC code: J01DH, 143 cases), and penicillins with extended spectrum (ATC code: J01CA, 103 cases). The adjusted RORs (95% confidence interval) in individuals using 1, 2, and ≥ 3 anti-infectives were 8.88 (7.05-11.18), 9.77 (6.89-13.86), and 18.39 (11.85-28.54), respectively. Moreover, 47.2% of CDACs occurred within 7 days of anti-infective therapy initiation. The adjusted ROR of interaction terms of ≥ 70 years × 1 drug was 21.81 (14.56-32.68).Conclusion: Our results suggest that the number of administered anti-infectives and patient age are associated with CDAC. These data may be particularly beneficial to prescribers and would contribute to improving the management of CDAC.

Stereotactic body radiotherapy for ventricular tachycardia (cardiac radiosurgery)

Single-session cardiac stereotactic body radiotherapy, called cardiac radiosurgery (CRS) or radioablation (RA), may offer apotential treatment option for patients with refractory ventricular tachycardia (VT) and electrical storm who are otherwise ineligible for catheter ablation. However, there is only limited clinical experience. We now present the first-in-patient treatment using (CRS/RA) for VT in Germany. A78-year-old male patient with dilated cardiomyopathy and significantly reduced ejection fraction (15%) presented with monomorphic VT refractory to poly-anti-arrhythmic medication and causing multiple implantable cardioverter-defibrillator (ICD) interventions over the course of several weeks, necessitating prolonged treatment on an intensive care unit. Ultra-high-resolution electroanatomical voltage mapping (EVM) revealed are-entry circuit in the cardiac septum inaccessible for catheter ablation. Based on the EVM, CRS/RA with asingle session dose of 25 Gy (83% isodose) was delivered to the VT substrate (8.1 cc) using ac-arm-based high-precision linear accelerator on November 30, 2018. CRS/RA was performed without incident and dysfunction of the ICD was not observed. Following the procedure, asignificant reduction in monomorphic VT from 5.0to 1.6episodes per week and of ICD shock interventions by 81.2% was observed. Besides periprocedural nausea with asingle episode of vomiting, no treatment-associated side effects were noted. Unfortunately, the patient died 57days after CRS/RA due to sepsis-associated cardiac circulatory failure after Clostridium difficile-associated colitis developed during rehabilitation. Histopathologic examination of the heart as part of aclinical autopsy revealed diffuse fibrosis on most sections of the heart without apparent differences between the target area and the posterior cardiac wall serving as acontrol. CRS/RA appears to be apossible treatment option for otherwise untreatable patients suffering from refractory VT and electrical storm. Arelevant reduction in VT incidence and ICD interventions was observed, although long-term outcome and consequences of CRS/RA remain unclear. Clinical trials are strongly warranted and have been initiated.

Clinical Guideline Highlights for the Hospitalist: Clostridium difficile Infections in Children.

Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). February 15, 2018 PRIOR VERSIONS: Cohen SH, Gerding DN, Johnson S, et al; Society for Healthcare Epidemiology of America; Infectious Diseases Society of America. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010; 31:431-55.Gerding DN, Johnson S, Peterson LR, et al. Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol 1995;16:459-477. IDSA and SHEA. Support for this guideline was provided by the IDSA and SHEA. Children and adults with Clostridium difficile infections.

Patient perception and approval of fecal microbiota transplantation (FMT) as an alternative treatment option for ulcerative colitis

Fecal microbiota transplantation (FMT) represents a treatment option for recurring Clostridium difficile-associated colitis. However, there is also evidence that FMT can be effective in treating ulcerative colitis. This study examined the approval and willingness of affected patients who underwent FMT. A standardized questionnaire containing 27 polar and open questions was dispatched to a cohort of 262 patients suffering from UC. It included questions regarding the FMT process, donors, and possible concerns. Additionally, aspects of social background and disease activity were addressed. The response rate was 31.3 % (n = 82). Forty-eight (58.5 %) patients were already aware of FMT. Forty-six (56.1 %) were willing to undergo FMT if given a respective indication. The effectiveness of the procedure (40.2 %), followed by failure of all other therapies (17.1 %), formed the principal motivation. The transmission of possible infectious agents (26.8 %), and the potential contamination of the stool graft leading to a deterioration of clinical symptoms, raised the most concerns. (20.7 %).The preferred delivery system of FMT was capsules (67.1 %), followed by colonoscopic application (47.6 %). The patients were in favour of a donor proposed by the physician (52,4 %). Willingness to undergo FMT did not differ significantly between genders (56.4 % women vs. 57.1 % men). Smokers (88.9 %), patients who did not watch television at all (77.8 %) and those with private health insurance, showed an increased willingness to undergo FMT. For the majority of the UC patients surveyed, FMT represents a feasible treatment option. Approximately half of the respondents would consider FMT as an alternative treatment option, even inspite of a satisfactory disease response to current standard therapies. Unsurprisingly, there are concerns regarding the transmission of possible infectious agents and the hygienic implementation of FMT itself.

Clostridioides difficile Infection in Chronic Kidney Disease/End-Stage Renal Disease.

Clostridioides difficile infection (CDI) is a major health-care burden and increasingly seen in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Increased antibiotic use, alteration in host defenses, and gastric acid suppression are some of the etiologies for increased risk of CDI in these populations. Patients with CKD/ESRD have a higher risk of initial episode, recurrence, and development of severe CDI than those without CKD or ESRD. Diagnosis and management of CDI in patients with CKD/ESRD are similar to that in the general population. The mortality, length of stay, and health-care costs are higher in patients with CDI and CKD/ESRD. Antimicrobial stewardship with reduction in antibiotic use along with infection-control measures such as contact isolation and hand hygiene with soap and water is essential in the control and prevention of CDI in patients with CKD/ESRD.

Correlation, consequence, and functionality in microbiome-immune interplay.

Correlation, consequence, and functionality in microbiome-immune interplay.

Clostridium difficile-Associated Colitis Post-Transplant Is Not Associated with Elevation of Tacrolimus Concentrations.

Diarrhea is a common condition after solid organ transplant (SOT); Clostridium difficile-associated colitis (CDAC) is one of the most common infections after SOT. We documented previously that some types of enteritis are associated with an elevation of tacrolimus (TAC) trough concentrations by interfering with the drug's complex metabolism. Tacrolimus concentrations of 25 SOT recipients including 12 renal and 13 liver recipients before, during, and after CDAC were analyzed retrospectively. Median age of the 25 patients was 54 y (range, 36-71), there were 15 males and 10 females. Clostridium difficile-associated colitis developed at a median of 55 d (range 2-4551) post-SOT. Median TAC concentrations prior to the outbreak of CDAC were 6.9 ng/mL (range, <1.5-17.2), 5.6 ng/mL (range, <1.5-13.2) during diarrhea, and 7.4 ng/mL (range, <1.5-24.3) after resolution of diarrhea (p > 0.05, NS). Treatment of CDAC consisted of metronidazole for 14 d in all cases. All patients recovered from CDAC but seven patients had CDAC relapse. In contrast to other types of infectious diarrhea such as rotavirus enteritis and cryptosporidiosis, CDAC is not associated with an increase in TAC concentrations. This is because C. difficile causes primarily colitis as opposed to other organisms, which are associated with enteritis.

RARE COMPLICATIONS OF THERAPY OF CYSTIC FIBROSIS: CLOSTRIDIUM DIFFICILE-ASSOCIATED COLITIS

The aim of this study was to determine a rate of Clostridium difficileassociated colitis in patients with cystic fibrosis (CF). Methods. Qualitative and quantitative bacteriological examination with identification of C. difficile toxins A and B production was done in 61 intestinal contents samples from CF patients who previously received antibiotics. Results. Various disorders of qualitative and quantitative composition of the intestinal microflora were found in 100% of patients. Testing for C. difficile toxins A and B production was positive in 5 (15.2%) of patients. Conclusion. These patients could have a high risk of pseudomembranous colitis development.

Successful treatments with polymyxin B hemoperfusion and recombinant human thrombomodulin for fulminant Clostridium difficile-associated colitis with septic shock and disseminated intravascular coagulation: a case report.

BackgroundClostridium difficile (CD)‐associated colitis (CDAC) is endemic and a common nosocomial enteric disease encountered by surgeons in modern hospitals due to prophylactic or therapeutic antibiotic therapies. Currently, the incidence of fulminant CDAC, which readily causes septic shock followed by multiple organ dysfunction syndromes, is increasing. Fulminant CDAC requires surgeons to perform a prompt surgery, such as subtotal colectomy, to remove the septic source. It is known that fulminant CDAC is caused by the shift from an inflammatory response at a local mucosal level to a general systemic inflammatory reaction in which CD toxin-induced mediators’ cascades disseminate. Recently, it has been proven that polymyxin B hemoperfusion (PMX-HP) improves septic shock and recombinant human thrombomodulin (rhTM) controls disseminated intravascular coagulation (DIC). In addition, clinically and basically, it has been shown that these treatments can control serous chemical mediators. Therefore, it is considered that these treatments are promising ones for patients with fulminant CDAC. In the current report, we present that these treatments without surgery contributed to the improvement of sepsis due to fulminant CDAC.Case presentationWe encountered a case who developed fulminant CDAC with septic shock and DIC after laparoscopic gastrectomy for gastric cancer. At admission to the intensive care unit, his APACHE II score was 22, which indicated an estimated risk of hospital death of 42.4 %. Our therapies were not the subtotal colectomy to remove septic sources but the combination treatments with both PMX-HP and rhTM. These combination therapies resulted in excellent outcomes, namely the dramatic improvement of septic shock and DIC and the patient’s survival. We speculate that these combination therapies completely inhibit the CD toxin-induced mediators’ cascades and correspond to the removal of septic sources.ConclusionsWe recommend both PMX-HP and rhTM for patients who develop fulminant CDAC with septic shock and DIC to increase the survival benefit and replace the need for surgical treatment.

Prognosis with Proton Pump Inhibitor Versus H2 Blocker Therapy in Clostridium Difficile Infection

An 83-year-old female patient recovered from her primary Clostridium difficile-associated colitis upon antibiotic treatment and the suspension of her regular proton pump inhibitor (PPI) therapy, and had a recurrence of the infection once PPI was restarted. After the treatment of the recurrent episode, the PPI was replaced with a histamine H2 receptor blocker, and she developed no more relapses. The switch from PPI to a H2 blocker may have been a recovery factor. More research is encouraged to clarify the extent of the suggested effect.

Therapeutic effects and the possible mechanism of fecal transplantation on rats with Clostridium difficile-associated pseudomembranous colitis

Objective To investigate the therapeutic effects and the possible mechanism of fecal transplantation on rats with Clostridium difficile-associated pseudomembranous colitis. Methods A total of 40 Sprague-Dawley rats were divided into four groups including the healthy control group, model group, fecal transplant treatment group and vancomycin treatment group. Rats in three experimental groups were subcutaneously injected with clindamycin phosphate (10 mg), followed by treatment with toxin producing Clostridium difficile (ACTT43255) enema 24 hours later. The rats in fecal transplant treatment group and vancomycin treatment group were respectively treated with fecal suspension and vancomycin one day after modeling. The rats were fasted for one day after the last administration and then executed. The levels of potassium ion (K), sodium ion (Na), albumin (ALB), white blood cells (WBC), C-reaction protein (CRP), interleukin-1β (IL-1β), interleukin-10 (IL-10), interleukin-12 (IL-12) and interleukin-17 (IL-17) as well as the percentage of neutrophils (N%) in serum samples were detected. The colon tissue samples were collected for pathology examination. Results The rat model of pseudomembranous colitis was successfully established by subcutaneous injection of clindamycin in combination with toxin-producing Clostridium difficile (ACTT43255) enema. The signs of intestinal inflammation including serious weight loss, remarkably shortened colon length and significantly increased colon wet weight index were observed in rats from the model group (P<0.05). Compared with the rats from model group, the rats received fecal transplant showed significantly increased levels of K, ALB, IL-10 and IL-10/IL-12 in serum and decreased levels of WBC, N%, CRP, IL-1β and IL-17 (P<0.05). Conclusion Fecal transplantation was proved to be an effective approach for the treatment of pseudomembranous colitis. The therapeutic mechanism might due to its impacts on serum inflammatory factors. Key words: Fecal transplantation; Pseudomembranous colitis; Inflammatory factor

Therapeutic targeting of bile acids.

The first objectives of this article are to review the structure, chemistry, and physiology of bile acids and the types of bile acid malabsorption observed in clinical practice. The second major theme addresses the classical or known properties of bile acids, such as the role of bile acid sequestration in the treatment of hyperlipidemia; the use of ursodeoxycholic acid in therapeutics, from traditional oriental medicine to being, until recently, the drug of choice in cholestatic liver diseases; and the potential for normalizing diverse bowel dysfunctions in irritable bowel syndrome, either by sequestering intraluminal bile acids for diarrhea or by delivering more bile acids to the colon to relieve constipation. The final objective addresses novel concepts and therapeutic opportunities such as the interaction of bile acids and the microbiome to control colonic infections, as in Clostridium difficile-associated colitis, and bile acid targeting of the farnesoid X receptor and G protein-coupled bile acid receptor 1 with consequent effects on energy expenditure, fat metabolism, and glycemic control.

Mo1227 Cathelicidin Mimic Ceragenin CSA13 Modulates Clostridium difficile Associated Colitis and Toxin a Mediated Enteritis in Mice

5-ASA levels increased after 1 h for Pentasa and Apriso and 3 h for Lialda. Prominent 5ASA and Ac-5-ASA release after Pentasa was observed at all GI sites (including gastric). Gastric 5-ASA levels were >170-fold higher after Pentasa vs. Lialda. Peak small bowel GI 5-ASA (Figure 1) and Ac-5-ASA (not shown) levels were 15 to 1000+ fold lower for Lialda vs. Pentasa and Apriso, emphasizing greater colon release for Lialda. In addition, peak GI Ac-5-ASA levels were seen earlier with Pentasa (4.0+2.0 h) vs. Apriso (7.0+0.0 h) and Lialda (6.0+1.4 h). Plasma 5-ASA and Ac-5-ASA levels were lower vs. GI fluids consistent with luminal actions (Table 1). As in GI fluids, plasma 5-ASA and Ac-5-ASA appeared earliest for Pentasa and latest for Lialda. Peak plasma levels occurred 12 h after Lialda, reflecting again mostly colon absorption. Conclusions: Using novel multiport catheters to aspirate GI fluids for regional drug release analysis, we showed variable time-dependent appearance and absorption of 3 mesalamine products. Release of 5-ASA and its metabolite occurred earliest and most proximally with Pentasa (including gastric release). Small bowel release and absorption were slower and more distal with Apriso and were minimal with Lialda. Such innovative in vivo techniques will be used to validate in vitro dissolution methods and support computational models for future processes that are applicable to developing luminally-acting and extended-release drugs. This research was funded by FDA grants HHSF223201000082C and HHSF223201300460A.

Probiotics for antibiotic-associated diarrhea: do we have a verdict?

Probiotics use has increased tremendously over the past ten years. This was coupled with a surge of data relating their importance in clinical practice. Antibiotic-associated diarrhea, whose frequency has risen recently, was one of the earliest targets with data published more than ten years ago. Unfortunately, available trials suffer from severe discrepancies associated with variability and heterogeneity of several factors. Most published randomized controlled trials and subsequent meta-analyses suggest benefit for probiotics in the prevention of antibiotic-associated diarrhea. The same seems to also apply when the data is examined for Clostridium difficile-associated colitis. However, the largest randomized double-blind placebo-controlled trial to date examining the use of a certain preparation of probiotics in antibiotic-associated diarrhea showed disappointing results, but it was flawed with several drawbacks. The commonest species of probiotics studied across most trials is Lactobacillus; however, other types have also shown similar benefit. Probiotics have enjoyed an impeccable safety reputation. Despite a few reports of severe infections sometimes leading to septicemia, most of the available trials confirm their harmless behavior and show similar adverse events compared to placebo. Since a consensus dictating its use is still lacking, it would be advisable at this point to suggest prophylactic use of probiotics to certain patients at risk for antibiotic-associated diarrhea or to those who suffered previous episodes.

Findings of a hospital surveillance-based outcome evaluation study for Clostridium difficile-associated colitis

We completed a prospective study of 164 patients involved in a Clostridium difficile surveillance programme, evaluating a range of variables such as disease severity, treatment regimen and known clinical risk factors, for their effect on case lethality. The aim of this study was to determine if there are any additional clinical variables worth considering for inclusion in the therapeutic decision-making process. Beyond common risk factors, secondary immunodeficiencies such as diabetes mellitus, malignancy, autoimmune disease, immunosuppressive therapy and chronic hepatitis were assessed. Overall case lethality was 23%. There was a suggestion that regular proton pump inhibitor use in past medical history might be associated with greater lethality. Immunosuppressive therapy within 1 month before the onset of diarrhoea was associated with a significant four-fold lethality increase. This last finding may have the potential to further improve therapeutic judgement if used as an explicit component of a revised scoring system. In relation to Clostridium difficile-associated colitis, immunosuppressive therapy as a red flag entity, as described here, has not been previously published.

Solid organ recipients are at increased risk for recurrent Clostridium difficile colitis

Background Solid organ transplant (SOT) recipients carry a high risk of developing Clostridium difficile-associated colitis (CDAC) and an increased risk for recurrence.

Fecal microbiota transplantation for Clostridium difficile-associated colitis in a severely immunocompromized critically ill AIDS patient

Fecal microbiota transplantation for Clostridium difficile-associated colitis in a severely immunocompromized critically ill AIDS patient

Toxic megacolon

Toxic megacolon represents a dreaded complication of mainly inflammatory or infectious conditions of the colon. It is most commonly associated with inflammatory bowel disease (IBD), i.e., ulcerative colitis or ileocolonic Crohn's disease. Lately, the epidemiology has shifted toward infectious causes, specifically due to an increase of Clostridium difficile-associated colitis possibly due to the extensive (ab)use of broad-spectrum antibiotics. Other important infectious etiologies include Salmonella, Shigella, Campylobacter, Cytomegalovirus (CMV), rotavirus, Aspergillus, and Entameba. Less frequently, toxic megacolon has been attributed to ischemic colitis, collagenous colitis, or obstructive colorectal cancer. Toxic colonic dilatation may also occur in hemolytic-uremic syndrome (HUS) caused by enterohemorrhagic or enteroaggregative Escherichia coli O157 (EHEC, EAEC, or EAHEC). The pathophysiological mechanisms leading to toxic colonic dilatation are incompletely understood. The main characteristics of toxic megacolon are signs of systemic toxicity and severe colonic distension. Diagnosis is made by clinical evaluation for systemic toxicity and imaging studies depicting colonic dilatation. Plain abdominal imaging is still the most established radiological instrument. However, computed tomography scanning and transabdominal intestinal ultrasound are promising alternatives that add additional information. Management of toxic megacolon is an interdisciplinary task that requires close interaction of gastroenterologists and surgeons from the very beginning. The optimal timing of surgery for toxic megacolon can be challenging. Here we review the latest data on the pathogenesis, clinical presentation, laboratory, and imaging modalities and provide algorithms for an evidence-based diagnostic and therapeutic approach.

H2 Receptor Blockade: A Risk Factor for Clostridium Difficile Associated Disease Severity?

Introduction: Clostridium difficile (CD) associated colitis (CDAC) is an increasing problem in seriously ill surgical patients. New acquisition of CD and antimicrobial exposure are paramount in the epidemiology of CDAC. in addition, acid suppression by H2 blockers or proton pump inhibitors has been implicated as an important risk factor. However, unique to H2 blockers is the suppression of mucus release by goblet cells in the intestine and defects in intestinal barrier function (in vitro study from our laboratory).

Efficacy of Infliximab Rescue Therapy in Hospitalized Patients with Steroid-Refractory Ulcerative Colitis: Single Center Experience

Background/Aims: In hospitalized patients with acute steroid-refractory UC, infliximab has been demonstrated to be one of the medical rescue therapies to avoid colectomy. We report the result of a retrospective observational study to find the efficacy and safety of infliximab as a rescue therapy in our hospital. Methods: Between January 2007 and January 2010, 9 hospitalized patients with steroid-refractory UC were selected to receive three infusions of infliximab (5 mg/kg), at weeks 0, 2, and 6. Efficacy of treatment was evaluated at 8 weeks after the first infliximab infusion and at the end of follow-up period. Adverse events related to infliximab rescue therapy were also collected. Results: Seven patients (77.8%) had completed 3 infusions of infliximab and achieved clinical response at 8 weeks after the first infliximab infusion. Clinical remission rate and the rate of mucosal healing at 8 weeks were 57.1% (4/7) and 71.4% (5/7), respectively. They were followed up for median time of 24.9 months (19.5-53.6 months). One patient underwent emergency colectomy at weeks 2, due to colon perforation, while another patient had discontinued infliximab treatment at weeks 4, because of Clostridium difficile-associated colitis. Finally, colectomy was avoided in 77.8% (7/9) of cases. There was no mortality. Conclusions: Rescue therapy with infliximab has sustained clinical benefit in 88.9% of our hospitalized patients with acute steroid-refractory UC. Future prospective and long-term follow-up trials with a large number of patients are needed to confirm the efficacy and safety of the treatment. (Intest Res 2012;10:152-160) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏