Clostridium difficile-associated diarrhea and colitis: clinical manifestations, diagnosis, and treatment

PURPOSE: This review examines the pathogenesis, clinical manifestations, diagnosis, and current medical and operative strategies in the treatment of Clostridium difficile diarrhea and colitis. Prevention and future avenues of research are also investigated. METHODS: A review of the literature was conducted with the use of MEDLINE. RESULTS: C. difficile is a gram-positive, spore-forming bacterium capable of causing toxigenic colitis in susceptible patients, usually those receiving antibiotics. Overgrowth of toxigenic strains may result in a spectrum of disease, including becoming an asymptomatic carrier, diarrhea, self-limited colitis, fulminant colitis, and toxic megacolon. Diagnosis requires a high index of suspicion and depends on clinical data, laboratory stool studies (enzyme-linked immunoabsorbent assay and cytotoxin test), and endoscopy in selected cases. Protocols for treatment of primary and relapsing infections are provided in algorithm format. Discontinuation of antibiotics may be enough to resolve symptoms. Medical management with oral metronidazole or vancomycin is the first-line therapy for those with symptomatic colitis. Teicoplanin, Saccharomyces spp. and Lactobacillus spp., and intravenous IgG antitoxin are reserved for more recalcitrant cases. Refractory or relapsing infections may require vancomycin given orally or other newer modalities. Fulminant colitis and toxic megacolon warrant subtotal colectomy. Cost, in terms of extended hospital stay, medical and surgical management, and, in some cases, ward closure, is thought to be formidable. Review of perioperative antibiotic policies and analysis of hospital formularies may contribute to prevention and decreased costs. CONCLUSION: C. difficile diarrhea and colitis is a nosocomial infection that may result in significant morbidity, mortality, and medical costs. Standard laboratory studies and endoscopic evaluation assist in the diagnosis of clinically suspicious cases. Appropriate perioperative antibiotic dosing, narrowing the antibiotic spectrum when treating infections, and discontinuing antibiotics at appropriate intervals prevent toxic sequelae.     

Small intestine in lymphocytic and collagenous colitis: mucosal morphology, permeability, and secretory immunity to gliadin

There is a recognised association between the "microscopic" forms of colitis and coeliac disease. There are a variety of subtle small intestinal changes in patients with "latent" gluten sensitivity, namely high intraepithelial lymphocyte (IEL) counts, abnormal mucosal permeability, and high levels of secretory IgA and IgM antibody to gliadin. These changes have hitherto not been investigated in microscopic colitis. Nine patients (four collagenous, five lymphocytic colitis) with normal villous architecture were studied. Small intestinal biopsies were obtained by Crosby capsule; small intestinal fluid was aspirated via the capsule. IEL counts were expressed per 100 epithelial cells, and intestinal IgA and IgM antigliadin antibody levels were measured by ELISA. Small intestinal permeability was measured by the lactulose:mannitol differential sugar permeability test. IEL counts were normal in all cases, median 17, range 7-30. Intestinal antigliadin antibodies were measured in six cases and were significantly elevated in two patients (both IgA and IgM). Intestinal permeability was measured in eight cases and was abnormal in two and borderline in one. These abnormalities did not overlap: four of nine patients had evidence of abnormal small intestinal function. Subclinical small intestinal disease is common in the two main forms of microscopic colitis.     

Ticlopidine induced cholestatic jaundice

Ticlopidine hydrochloride (Ticlid) has been increasingly used as an antiplatelet agent. Some studies showed that it has higher efficacy in reducing stroke recurrence when compared to conventional aspirin. Side effects like gastrointestinal disturbances and blood dyscrasias are common but ticlopidine-induced cholestatic jaundice has been reported only rarely. We present a case report on a patient who has ticlopidine-induced cholestatic jaundice.     

Constipation, diarrhea, and irritable bowel syndrome

Constipation, diarrhea, and irritable bowel syndrome are commonly encountered in the primary care practice. Most episodes of constipation and diarrhea are benign and self-limited. Patients with chronic constipation should undergo a screening evaluation to exclude organic disease, after which most can be managed successfully with dietary modification and fiber supplementation. The cause of chronic diarrhea usually can be discerned clinically, with irritable bowel syndrome, inflammatory bowel disease, and lactose intolerance being diagnosed most frequently. Irritable bowel syndrome is a functional gastrointestinal disorder characterized by abdominal pain and disordered defecation, which is successfully managed with a strong physician-patient relationship and periodic pharmacologic intervention.     

Febrile state, bloody diarrhea and megacolon

We report about a forty year old female patient with severe bloody diarrhoea and fever over a period of 14 days due to an infection with Salmonella enteritidis. X-ray of the abdomen showed a toxic megacolon. With the diagnosis of an infectious colitis we started therapy with ciprofloxacin i/v. The toxic megacolon progressed despite intensive care and parenteral nutrition. Additionally the patient received metronidazole i/v and in combination with a roll technique in bed in the knee-elbow-position the leucocytosis and the megacolon decreased. A toxic megacolon is in about 3% associated with an infection with Salmonella enteritidis. It is essentially diagnosed by X-ray. Patients should receive intensive care, and because of the high mortality rate an interdisciplinary management is required. The article discusses the major differential diagnosis of the toxic megacolon, as well as the pathogenesis and therapy of Salmonella ent, infection. In case of an infection with Salmonella ent. physicians should acknowledge the possibility of development of a toxic megacolon.     

Travelers' diarrhea. Epidemiology, prevention, and self-treatment

Risk factors for travelers' diarrhea include adventurous behavior, consumption of unclean water or food, and special hosts like those taking long acting H2 blockers. Approaches to prevention include education about risk factors, which often fails to lead to modification of risky behavior, and chemoprophylaxis with bismuth subsalicylate-containing compounds or antimicrobial agents. Chemoprophylaxis is generally discouraged except in special circumstances and in high-risk hosts. Self-treatment of travelers' diarrhea is successful in limiting the course of diarrhea and minimizing losses of vacation and business time. Current therapeutic options, in order of increasing effectiveness, include attapulgite, BSS-containing compounds, loperamide, antimicrobial agents such as the fluoroquinolones, and the combination of loperamide and an antimicrobial agent. Under study are a nonabsorbed antimicrobial agent, rifaximin, and a novel calmodulin inhibitor, zaldaride. Development and evaluation of vaccines against enterotoxigenic Escherichia coli and Shigella are proceeding apace but are not yet available for routine use.     

Ticlopidine facilitates the deaggregation of human platelets aggregated by thrombin

Eleven patients with moderate to severe hypertension were studied at the Vargas Hospital of Caracas. The patients were pretreated with labetalol, 800 to 1200 mg/day, orally, over a period of 1 week, after which an intravenous infusion of dopamine, .5 to 3 micrograms/kg/minute, was given. Two intravenous dopamine infusions (30 minutes each) were performed before and after the injection of metoclopramide (30 mg, intravenous bolus). Two washout periods were also included before and after metoclopramide administration. Dopamine induced a decrease of blood pressure from 171.9 + 6.35/103.6 +/- 3.12 to 152.7 +/- 7.55/93.8 +/- 2.97 mm Hg (P < .001) without altering heart rate, and it increased plasma insulin levels from 8.29 +/- .70 microU/mL to 12.09 +/- 1.83 microU/mL (P < .01). Metoclopramide caused no changes of blood pressure or plasma insulin levels. Hypotensive responses and plasma insulin increases due to dopamine were blocked by metoclopramide, however. The authors conclude that a dopaminergic receptor may be involved in some cardiovascular responses and in modulating insulin secretion in humans.