s-1743 and Enterocolitis--Pseudomembranous

Clostridium difficile is currently the leading cause of infectious diarrhea in hospitalized patients. In addition to the infection due to toxigenic C. difficile in the gastrointestinal tract of susceptible hosts, other predisposing factors for C. difficile infection (CDI) are identified, including advanced age, a prolonged hospital stay, and use of acid-suppressive drugs. Of note, exposure to gastric acid-reducing agents, such as H2 blockers and proton pump inhibitors (PPIs), remains a controversial risk factor, and has been associated with CDI in some studies but not in others. A mouse model of antibiotic-associated clostridial colitis was established to examine the role of PPIs for CDI.. A mouse model of antibiotic-associated clostridial colitis was set up. NF-κB reporter mice were used to address the in vivo spatial and temporal inflammatory patterns of C. difficile-associated colitis. Serum levels of lipopolysaccharide and dextran-FITC were measured to reflect the barrier permeability of affected intestines.. Mice with CDI that were exposed to PPI exhibited greater losses of stool consistency and body and cecal weights than those that were not exposed to PPI. Further, more neutrophilic infiltrations, epithelial damage, and inflammatory cytokine expression were noted in colon specimens of the mice with PPI exposure. More-evident inflammatory responses were detected by in vivo imaging of NF-κB reporter mice with CDI that were exposed to PPI. Gut barrier permeability was increased to a greater extent, as reflected by higher serum levels of lipopolysaccharide and dextran-FITC in mice with CDI that were exposed to PPI.. Our mouse model demonstrates that PPI exposure increases the severity of intestinal inflammation in mice with C. difficile-associated colitis.

Topics: Animals; Anti-Bacterial Agents; Clostridioides difficile; Colon; Cytokines; Disease Models, Animal; Enterocolitis, Pseudomembranous; Esomeprazole; Feces; Gene Expression Regulation, Bacterial; Genes, Reporter; Goblet Cells; Mice; NF-kappa B; Proton Pump Inhibitors; Up-Regulation

Patients with cystic fibrosis (CF) have several risk factors for Clostridium difficile colonization such as frequent hospitalization and exposure to a broad array of antibiotics utilized for the control, eradication, and prophylaxis of respiratory pathogens. However, despite this high rate of colonization, the occurrence of C. difficile infection (CDI) in CF is rare. We report three children with CF who presented with severe community-associated CDI. All three children had complicated courses and one died. These children were in good health without significant morbidities, and were not frequently hospitalized nor did they receive frequent antibiotic courses. The occurrence of 3 severe cases within a 15-month period prompted us to report these cases and review the literature in regard to CDI. We reviewed the CF GI tract as possible risk factors for a high rate of C. difficile colonization in individuals with CF. Since a high percentage of individuals with CF are on gastric acid blocking agents, we also focused on gastric acid suppression as a potential risk factor for CDI.

Topics: Adolescent; Antacids; Biopsy; Child; Clostridioides difficile; Colon; Cystic Fibrosis; Enterocolitis, Pseudomembranous; Esomeprazole; Fatal Outcome; Female; Gastric Acid; Humans; Infant; Male; Megacolon, Toxic; Proton Pump Inhibitors; Risk Factors

After an accepted technique of abdominoplasty, a 66-year-old woman developed Clostridium difficile-associated diarrhea, leading to toxic megacolon and subsequent subtotal colectomy. The presumed etiology is chronic use of a proton pump inhibitor. This was addressed in a 2012 "white paper" warning issued by the Food and Drug Administration. This article presents the course of this case as well as a review of the pertinent literature.

Topics: Abdominoplasty; Aged; Colectomy; Enterocolitis, Pseudomembranous; Esomeprazole; Female; Humans; Intestinal Mucosa; Megacolon, Toxic; Necrosis; Proton Pump Inhibitors

Clostridium difficile is a gram-positive, anaerobic, spore-forming, rod-shaped bacterium responsible for most of the hospital-acquired diarrhea in developed countries. The organism received its name because it was difficult to isolate and grow in culture. Infections in the elderly have been associated with significant morbidity and mortality as well as prolonged hospitalization.. A 72-year-old white male presented with a 5-day history of abdominal pain, nausea, and severe diarrhea but no fever or chills. He had had recent chemotherapy for Merkel cell carcinoma of the right ear. Medical history included hypothyroidism for 10 years and non-Hodgkin's lymphoma in remission for 4 years after a stem cell transplant. The patient was receiving oral vancomycin, levofloxacin, thyroxine, and esomeprazole. He had severe infection secondary to chemotherapy for Merkel cell carcinoma; in addition, he had failed to respond to metronida-zolc and vancomycin treatment, with the resulting development of colon dilatation and hypoalbuminemia. Colonoscopy showed severe ulceration with inflammation suggestive of severe persistent colitis. At that point, the patient was given 1 dose of IV immunoglobulin (IVIG) 400 mg/kg; vancomycin treatment was continued. Two days after IVIG therapy, the patient's diarrhea improved, with complete resolution after 6 days; bowel dilatation resolved completely after 7 days; and oral intake improved after 2 days. The patient continued on a tapering dose of vancomycin for 6 weeks. He was discharged home and had no recurrence despite antibiotic use for pseudomonas and staphylococcus bacteremia.. Severe C difficile colitis has been reported more frequently in the literature recently, especially in elderly patients. Tissue culture assay is the best diagnostic test to detect the cytotoxin; enzyme immunoassay is the test used in most hospitals, but it has a sensitivity of only -75%. Treatment options remain limited to eradicate this serious infection. Antibiotic therapy, infection control measures, and early diagnosis are essential components of successful outcome for this disease. This patient's infection resolved with the addition of IVIG with no recurrence, suggesting the possible benefit of this treatment in certain patients with severe colitis who do not respond to standard therapy.

Topics: Aged; Anti-Bacterial Agents; Carcinoma, Merkel Cell; Clostridioides difficile; Cytotoxins; Diarrhea; Ear Neoplasms; Enterocolitis, Pseudomembranous; Esomeprazole; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Levofloxacin; Male; Metronidazole; Ofloxacin; Skin Neoplasms; Thyroxine; Vancomycin