| Patient Education |
|
Click here for patient education.
|
|
You are in: eMedicine Specialties >
Gastroenterology > Colon
Clostridium Difficile Colitis
Article Last Updated: Aug 10, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Craig A Gronczewski, MD, Clinical Assistant Professor, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey; Consulting Staff, Princeton Medical Center; Consulting Staff, Robert Wood Johnson University Hospital
Craig A Gronczewski is a member of the following medical societies: Alpha Omega Alpha and American College of Emergency Physicians
Coauthor(s):
Jonathan P Katz, MD, Assistant Professor of Medicine, Department of Medicine, University of Pennsylvania School of Medicine
Editors: Waqar A Qureshi, MD, Chief of Endoscopy, Associate Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine and VA Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; BS Anand, MD, Department of Internal Medicine, Division of Gastroenterology, Professor, Baylor University College of Medicine; Alex J Mechaber, MD, FACP, Assistant Dean for Medical Curriculum, Associate Professor of Medicine, Division of General Internal Medicine, University of Miami Miller School of Medicine; Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Author and Editor Disclosure
Synonyms and related keywords:
C difficile, gut flora, antibiotic-associated diarrhea, pseudomembranous colitis, cephalosporins, ampicillin, amoxicillin, clindamycin, macrolides, erythromycin, clarithromycin, azithromycin, aminoglycosides, fluoroquinolones, trimethoprim-sulfamethoxazole, metronidazole, chloramphenicol, tetracycline, imipenem, meropenem, Clostridium Difficile colitis, C Difficile colitis, nosocomial infections, fulminant life-threatening colitis, toxin A, enterotoxin, toxin B, cytotoxin, C difficile infection, cramping abdominal pain, mild-to-moderate watery diarrhea, colonic perforation, peritonitis, hemolytic-uremic syndrome, necrotizing enterocolitis, Hirschsprung disease, inflammatory bowel disease
Background
Clostridium difficile is a gram-positive, anaerobic, spore-forming bacillus that is responsible for the development of antibiotic-associated diarrhea and colitis. C difficile was first described in 1935 as a component of the fecal flora of healthy newborns and was initially not thought to be a pathogen. It was named difficile because it grows slowly and is difficult to culture. While early investigators noted that the bacterium produced a potent toxin, the role of C difficile in antibiotic-associated diarrhea and pseudomembranous colitis was not elucidated until the 1970s.
C difficile infection commonly manifests as mild-to-moderate diarrhea, occasionally with abdominal cramping. Pseudomembranes, adherent yellowish-white plaques on the intestinal mucosa, occasionally are observed. In rare cases, patients with C difficile infection can present with an acute abdomen and fulminant life-threatening colitis. Approximately 20% of individuals who are hospitalized acquire C difficile during hospitalization, and more than 30% of these patients develop diarrhea. Thus, C difficile colitis is currently one of the most common nosocomial infections.
The diagnosis of C difficile colitis should be suspected in any patient with diarrhea who has received antibiotics within the previous 2 months and/or when diarrhea occurs 72 hours or more after hospitalization.
Pathophysiology
C difficile colitis results from a disturbance of the normal bacterial flora of the colon, colonization with C difficile, and release of toxins that cause mucosal inflammation and damage. Antibiotic therapy is the key factor that alters the colonic flora. Hospitalized patients are the primary targets of C difficile infection. C difficile is present in 2-3% of healthy adults and in as many as 70% of healthy infants. Treatment of asymptomatic carriers is not recommended. Colonization occurs by the fecal-oral route. C difficile forms heat-resistant spores that can persist in the environment for several months to years. Outbreaks of C difficile diarrhea may occur in hospitals and other outpatient facilities where contamination with spores is prevalent. Normal gut flora resists colonization and overgrowth with C difficile. Antibiotic use, which suppresses the normal flora, allows proliferation of C difficile.
Pathogenic strains of C difficile produce 2 distinct toxins. Toxin A is an enterotoxin, and toxin B is a cytotoxin. Both are high–molecular weight proteins capable of binding to specific receptors on the intestinal mucosal cells. Receptor-bound toxins gain intracellular entry where they catalyze a specific alteration of Rho proteins, small glutamyl transpeptidase (GTP)–binding proteins that assist in actin polymerization, cytoskeletal architecture, and cell movement. Both toxin A and toxin B appear to play a role in the pathogenesis of C difficile colitis in humans.
Frequency
United States
C difficile infection primarily occurs in hospitalized patients, causing as many as 3 million cases of diarrhea and colitis per year. McFarland et al (1989) reported that 7% of patients admitted to a hospital and 28% of patients who were hospitalized had positive cultures for the organism. Approximately one third of these patients developed diarrhea. According to one report, only 20,000 cases per year are diagnosed in outpatients.
International
Incidence is highly variable and depends on multiple factors, including the frequency with which endoscopy is used to establish the diagnosis, antimicrobial use patterns, and epidemiologic patterns.
Mortality/Morbidity
While most patients with C difficile colitis recover without specific therapy, symptoms may be prolonged and debilitating. C difficile associated diarrhea can be a serious condition with a mortality rate of up to 25% in elderly patients who are frail. Reports that focus on patients who are more seriously ill indicate mortality rates of 10-30%.
Sex
C difficile colitis has no sexual predilection.
Age
C difficile infection is more common in elderly people, and old age may promote susceptibility to colonization and disease. While infants and young children frequently harbor C difficile and its toxins, clinical infection is uncommon. Cross-infection by C difficile is common in neonatal units, but neonates do not seem to develop C difficile associated diarrhea.
History
C difficile colonization results in a wide spectrum of clinical conditions, including an asymptomatic carrier state, mild self-limited diarrhea, pseudomembranous colitis, and fulminant colitis.
- Most patients develop diarrhea during or shortly after starting antibiotics. However, 25-40% of patients may not become symptomatic for as many as 10 weeks after completing antibiotic therapy.
- Symptoms often include the following:
- Mild-to-moderate watery diarrhea that is rarely bloody
- Cramping abdominal pain
- Anorexia
- Malaise
- Fever, especially in more severe cases
Physical
- Physical examination may reveal the following:
- Fever
- Dehydration
- Lower abdominal tenderness
- Rebound tenderness - Raises the possibility of colonic perforation and peritonitis
Causes
C difficile colitis results from a disruption of the normal bacterial flora of the colon, colonization with C difficile, and release of toxins that cause mucosal inflammation and damage.
- The chief risk factor for the disease is prior exposure to antibiotics.
- The most common antibiotics implicated in C difficile colitis include cephalosporins (especially second and third generation), ampicillin/amoxicillin, and clindamycin.
- Less commonly implicated antibiotics are the macrolides (ie, erythromycin, clarithromycin, azithromycin) and other penicillins.
- Agents occasionally reported to cause the disease include aminoglycosides, fluoroquinolones, trimethoprim-sulfamethoxazole, metronidazole, chloramphenicol, tetracycline, imipenem, and meropenem.
- Even brief exposure to any single antibiotic can cause C difficile colitis.
- A prolonged antibiotic course or the use of 2 or more antibiotics increases the risk of disease.
- Even antibiotics traditionally used to treat C difficile colitis have been shown to cause disease.
- Other risk factors include the following:
- Advanced age (>60 y)
- Hospitalization (particularly sharing a hospital room with an infected patient, intensive care unit stays, and prolonged hospital stays)
- Rarer associations include the following:
- Antineoplastic agents, principally methotrexate
- Hemolytic-uremic syndrome
- Malignancies
- Intestinal ischemia
- Renal failure
- Necrotizing enterocolitis
- Hirschsprung disease
- Inflammatory bowel disease
- Nonsurgical gastrointestinal procedures, including nasogastic tubes
Crohn Disease
Diverticulitis
Gastroenteritis, Viral
Inflammatory Bowel Disease
Intra-abdominal Sepsis
Irritable Bowel Syndrome
Malabsorption
Megacolon, Toxic
Pseudomembranous Colitis
Pseudomembranous Colitis
Salmonellosis
Shigellosis
Ulcerative Colitis
Vibrio Infections
Lab Studies
- Electrolytes: Dehydration and electrolyte imbalance may accompany severe disease.
- Albumin: Hypoalbuminemia and anasarca may accompany severe disease.
- CBC count: Leukocytosis may be present.
- Stool examination
- Stool may be hemoccult positive in severe colitis, but grossly bloody stools are unusual.
- Fecal leukocytes are present in about half of the cases.
- Stool assays for C difficile
- The stool cytotoxin test has high sensitivity and specificity (ie, 94-100% and 99% respectively) and is the test of choice. Diarrheal stool is filtered and then added to cultured fibroblasts. A positive test result is the demonstration of a cytopathic effect that is neutralized by specific antiserum. This test result is reported only as positive or negative, it is expensive, and it requires an overnight incubation and a tissue culture facility.
- Several commercial enzyme immunoassays are now available and provide more rapid results at less cost with reasonable sensitivity (ie, 69-87%) and specificity (ie, 99-100%). Because of the lower sensitivity, repeating this test may be necessary in patients in whom the pretest probability of C difficile infection is high and an initial test result is negative.
- The latex agglutination test cannot be used to detect toxins but instead detects the presence of glutamate dehydrogenase produced by C difficile. The sensitivity of this test is 48-59%, and the specificity is 95-96%. This test is not recommended.
- Stool cultures are not helpful because nontoxigenic strains of C difficile exist.
Procedures
- Endoscopy
- Endoscopy may demonstrate the presence of raised, yellowish-white, 2- to 10-mm plaques overlying an erythematous and edematous mucosa. These plaques are termed pseudomembranes.
- Pseudomembranes are observed in 14-25% of patients with mild disease and 87% of patients with fulminant disease.
- Most patients have disease throughout the colon. However, sigmoidoscopy alone may not reveal any abnormality if the disease is confined to the right colon. Typical pseudomembranes are beyond the limit of the flexible sigmoidoscopy in 10% of patients. Therefore, colonoscopy is more useful.
- Endoscopic examination findings may be normal in patients with mild disease or may demonstrate nonspecific colitis in moderate cases.
- Sigmoidoscopy and colonoscopy in patients with fulminant colitis may be contraindicated because of the risk of perforation. Limited proctoscopy, with minimal air insufflation, may be a useful diagnostic tool.
Histologic Findings
Biopsy of pseudomembranous plaques reveals an inflammatory exudate composed of mucinous fibrinous material containing polymorphonuclear cells.
Medical Care
The decision to treat C difficile infection and the type of therapy may depend on the severity of the disease.
- No treatment is necessary for asymptomatic carriers.
- Cessation of the causative antibiotic is essential when possible.
- Cessation may be the only treatment necessary for those with mild antibiotic-associated diarrhea without fever, abdominal pain, or leukocytosis.
- This conservative approach allows for reconstitution of the normal colonic microflora and markedly reduces the risk of relapse.
- Patients with more severe diarrhea or colitis should receive antibiotic therapy directed at C difficile. More than 95% of patients respond to 10 days of treatment with vancomycin (oral) or metronidazole (oral or intravenous). Symptomatic improvement can be expected within 2-3 days. Prompt therapy with vancomycin (oral) or metronidazole may control the colitis and prevent perforation in severe cases.
- In general, relapse is common and occurs in 5-50% of cases. Relapse typically occurs 3 days to 3 weeks after treatment is discontinued. Possible reasons for relapse include failure to eradicate the organism from the colon and reinfection from the environment.
Surgical Care
Fulminant colitis and toxic megacolon may require operative intervention.
Consultations
- Gastroenterologist - For consideration of colonoscopy in problematic disease
- Surgeon - For cases of suspected fulminant colitis, toxic megacolon, or peritonitis
The pharmacologic therapy should be tailored according to the severity of C difficile infection. Treatment is not indicated for asymptomatic carriers. In mild cases (ie, patients without fever, abdominal pain, or leukocytosis), cessation of causative antibiotics may be the only treatment necessary. Approximately 15-25% of patients respond to conservative therapy, which allows for reconstitution of normal colonic flora and reduces the risk of relapse.
Specific therapy aimed at eradicating C difficile is indicated if symptoms are persistent or severe or if antibiotics cannot be discontinued safely.
PO metronidazole and vancomycin are equally effective in treating diarrhea caused by C difficile. The PO administration of these medications is the preferred route because C difficile remains within the colonic lumen without invading the colonic mucosa. Vancomycin is poorly absorbed in the intestinal tract, thereby promoting high concentrations within the intestines while significantly reducing the prevalence of adverse systemic effects. Metronidazole, despite the incidence of systemic adverse effects and isolation of metronidazole-resistant strains of C difficile, is the drug of first choice because of its lower cost.
For patients who are unable to tolerate PO medication, IV metronidazole is effective. Excretion of the drug into bile and exudation from the inflamed colon results in bactericidal levels in feces. IV vancomycin is ineffective.
Antibiotic treatment for mild relapses may not be necessary because they often resolve spontaneously. For patients with more severe or persistent diarrhea or evidence of overt colitis, a second course of metronidazole or vancomycin is indicated. Treatment with vancomycin for relapse after metronidazole therapy is not necessary because development of antibiotic resistance is not usually the cause of relapse. Unfortunately, some patients may experience further relapses after antibiotic therapy is again discontinued.
Alternative and less frequently employed therapies include bacitracin, teicoplanin, and cholestyramine (an anion exchange resin) and bacteriotherapy.
Bacitracin is more costly and less effective than metronidazole and, therefore, is not first-line therapy.
Teicoplanin, a glycopeptide antibiotic similar to vancomycin, is not clinically available in the United States. While it is 4 times more potent than vancomycin in vitro, teicoplanin is no more effective than vancomycin (as demonstrated in a prospective study), is quite expensive, and may lead to the development of resistant enterococcal strains.
Cholestyramine binds toxins A and B of C difficile, but the clinical experience of different investigators has shown marked variation in results. Cholestyramine binds vancomycin and should not be used concurrently with vancomycin therapy.
Currently, using Saccharomyces boulardii in the treatment of this disease has generated interest because it seems to inhibit the effects of toxins A and B on the human colonic mucosa.
Bacteriotherapy with fecal enemas has been tried but is limited by the risk of hepatitis and retrovirus transmission, and administration of other bacterial preparations currently is under investigation.
Avoid antidiarrheal agents (eg, diphenoxylate with atropine). They have been reported to increase the duration and severity of symptoms.
Drug Category: Antibiotics
To eradicate C difficile infection and/or promote restoration of normal colonic flora.
| Drug Name | Metronidazole (Flagyl) |
|---|
| Description | Recommended as the treatment of choice for mild-to-moderate cases. Provides effective therapy, with reported response rates from 95-100%. In vitro activity is bactericidal and dose dependent. Standard dosing has been shown to promote fecal concentrations capable of a 99.99% reduction of C difficile. Relatively inexpensive (approximate wholesale cost for a 10-d supply is $1). Metronidazole IV may be administered to those patients who cannot tolerate PO medications because of its potential to accumulate in the inflamed colon. IV route is not as effective as PO. |
|---|
| Adult Dose | 500 mg PO tid or 250 mg PO qid for 10-14 d
500 mg IV qid for 10-14 d |
|---|
| Pediatric Dose | Not established |
|---|
| Contraindications | Documented hypersensitivity |
|---|
| Interactions | May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity of metronidazole; disulfiram reaction may occur with orally ingested ethanol |
|---|
| Pregnancy | B - Usually safe but benefits must outweigh the risks.
|
|---|
| Precautions | Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy |
|---|
| Drug Name | Vancomycin (Vancocin) |
|---|
| Description | Has excellent in vitro activity against C difficile. Kills organism by inhibiting cell wall synthesis. Significant luminal levels after PO vancomycin can be obtained because it is poorly absorbed from the GI tract. Major disadvantage is cost. PO vancomycin is relatively expensive, with a wholesale cost of approximately $150 for a 10-d supply. Because of the cost and the concern over the emergence of vancomycin-resistant enterococci strains, its use should be reserved for patients who cannot tolerate metronidazole, patients who do not respond to metronidazole, pregnant patients, and patients <10 y. Also preferred for severe cases and in patients who are high risk. Unlike IV metronidazole, IV vancomycin is not excreted into the GI lumen; therefore, it is difficult to deliver effective doses by this route. |
|---|
| Adult Dose | 125 mg PO qid for 10-14 d |
|---|
| Pediatric Dose | 40 mg/kg/d PO divided tid/qid for 7-10 d; not to exceed 2 g/d |
|---|
| Contraindications | Documented hypersensitivity |
|---|
| Interactions | Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; when taken concurrently with aminoglycosides, the risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; its effect on neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants |
|---|
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
|---|
| Precautions | Caution in renal failure and neutropenia; red man syndrome is caused by too rapid IV infusion (dose administered over a few min) but rarely happens when dose is administered as 2-h administration or as PO or IP administration; red man syndrome is not an allergic reaction; clinically significant serum levels have been reported in those taking multiple PO doses and in those with active inflammatory bowel disease (monitoring of serum levels in these patients may be appropriate); adverse reactions (eg, nephrotoxicity, ototoxicity, neutropenia) associated with IV therapy are rarely reported with PO administration |
|---|
| Drug Name | Bacitracin (Baciguent) |
|---|
| Description | Inhibits formation of major components of the bacterial cell wall and is bactericidal.
Alternative therapy, but it is expensive, not as effective as metronidazole or vancomycin in clinical trials, and without sufficient data to warrant its use. Drug is bitter and must be specially prepared in capsule form to prevent nausea. Bacitracin administered PO is only negligibly absorbed from the GI tract. |
|---|
| Adult Dose | 25,000 U PO qid for 10 d |
|---|
| Pediatric Dose | Not established |
|---|
| Contraindications | Documented hypersensitivity; vaccinia; varicella; epithelial herpes simplex keratitis; mycobacterial infections; fungal diseases of the eye; patients using steroid combinations after uncomplicated removal of a corneal foreign body |
|---|
| Interactions | None reported |
|---|
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
|---|
| Precautions | Highly nephrotoxic when administered systemically |
|---|
Drug Category: Anion exchange resins
Bind C difficile toxin and other proteins.
| Drug Name | Cholestyramine (Questran) |
|---|
| Description | For diarrhea associated with pseudomembranous colitis. Forms a nonabsorbable complex with bile acids in the intestine, which, in turn, inhibits enterohepatic reuptake of intestinal bile salts.
Also binds vancomycin, which precludes combination therapy. Available as a powder that must be mixed with water prior to ingestion. Efficacy is inferior to metronidazole or vancomycin, but it may have a role under certain circumstances (eg, patients who continue to relapse). Not absorbed from the GI tract. |
|---|
| Adult Dose | 4 g PO tid for 10-14 d |
|---|
| Pediatric Dose | Not established |
|---|
| Contraindications | Documented hypersensitivity; complete biliary obstruction |
|---|
| Interactions | May delay or reduce the absorption of concomitant PO medications, including phenylbutazone, warfarin, thiazide diuretics, propranolol, tetracycline, penicillin G, phenobarbital, thyroxine, estrogens, progestins, and digitalis |
|---|
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
|---|
| Precautions | Because cholestyramine binds bile acids, it may interfere with normal digestion and absorption of fat-soluble vitamins (eg, A, D, E, K); because cholestyramine may bind other drugs, patients should take other drugs at least 1 h before or 4-6 h after its administration; long-term use may be associated with increased bleeding tendency associated with vitamin K deficiency; reduction of serum folate has been reported with long-term use; caution in renal insufficiency or volume depletion |
|---|
Further Inpatient Care
- The development of dehydration, electrolyte disturbances, and worsening clinical condition may necessitate inpatient management.
Deterrence/Prevention
- C difficile is now recognized as a major nosocomial pathogen, and universal precautions should be implemented. The following guidelines are recommended when dealing with patients with C difficile colitis:
- Use disposable gloves, laboratory coats, and proper washing techniques.
- Educate the medical and nursing staff regarding the disease and its epidemiology.
- The mode of hospital transmission is unclear, but spores survive on inanimate objects. Therefore, close attention to cleanliness and disinfective measures are important.
- Enteric isolation of patients who are infected is recommended but is often impractical at most hospitals.
- More aggressive control measures, such as treatment of asymptomatic carriers, might be considered in a severe epidemic.
- The most important preventive measure is judicious use of antimicrobial agents.
Complications
- Fulminant colitis is a rare form of C difficile infection, occurring in only 3% of patients but accounting for most of the serious complications. These include toxic megacolon, colonic perforation, and death. Surgical intervention may be required.
- Toxic megacolon is diagnosed clinically in a patient with signs and symptoms of severe toxicity, the presence of a tender abdomen, and a dilated colon on plain radiograph of the abdomen.
- Colonic perforation is usually accompanied by abdominal rigidity, involuntary guarding, rebound tenderness, and absent bowel sounds. Free air may be revealed on abdominal radiographs. Any suspicion of perforation in this setting should prompt immediate surgical consultation.
Prognosis
- Most patients with C difficile colitis recover, even without specific therapy. However, persistent diarrhea may be debilitating and can last for several weeks.
- By using oral metronidazole or vancomycin, response rates greater than 95% are obtained, with symptomatic improvement in as little as 2-3 days and complete resolution in 7-10 days.
- Approximately 15-20% of patients treated for a first episode of C difficile colitis relapse following successful therapy. Relapse is manifested by return of symptoms, usually occurring within a week of completing treatment.
- Patients who relapse once are at an even greater risk of further relapses. The relapse rate for those with 2 or more relapses is 65%.
Medical/Legal Pitfalls
- C difficile colitis is a rare disorder that is best prevented by avoiding indiscriminate use of antibiotics. The risk of developing the disease should be explained to patients who are being prescribed antibiotics.
Special Concerns
- Relapse infection: No uniform recommendation exists for management of relapse. Relapse is probably due to persistence of the original C difficile strain. These organisms do not display in vitro resistance to metronidazole or vancomycin. Mild relapses may be managed without further antibiotic therapy. Patients with severe or persistent symptoms may be treated with a repeat 10- to 14-day course of metronidazole or vancomycin. Repeated relapses may be treated with a combination of vancomycin (same dose as before) and rifampin 600 mg bid for 7-10 days.
| Media file 1:
Endoscopic visualization of pseudomembranous colitis, a characteristic manifestation of full-blown Clostridium difficile colitis. Classic pseudomembranes are visible as raised yellow plaques ranging from 2-10 mm in diameter and scattered over the colorectal mucosa. Courtesy of Gregory Ginsberg, MD, University of Pennsylvania. |
 |  View Full Size Image | |
Media type: Photo
|
- Bartlett JG. Pseudomembranous enterocolitis and antibiotic-associated colitis. In: Feldman M, Scharschmidt BF, Sleisenger MH, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 6th ed. Philadelphia, Pa:. WB Saunders Co;1998:1633-1647.
- Cleary RK. Clostridium difficile-associated diarrhea and colitis: clinical manifestations, diagnosis, and treatment. Dis Colon Rectum. Nov 1998;41(11):1435-49. [Medline].
- Fekety R. Guidelines for the diagnosis and management of Clostridium difficile- associated diarrhea and colitis. American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. May 1997;92(5):739-50. [Medline].
- Gilbert DN, Moellering RC, Sande MA. The Sanford Guide to Antimicrobial Therapy. 13th ed. Hyde Park, Vt:. Antimicrobial Therapy;2000:12.
- Johnson S, Gerding DN. Clostridium difficile--associated diarrhea. Clin Infect Dis. May 1998;26(5):1027-34; quiz 1035-6. [Medline].
- Jones EM, Kirkpatrick BL, Feeney R. Hospital-acquired Clostridium difficile diarrhoea. Lancet. Apr 19 1997;349(9059):1176-7. [Medline].
- Kelly CP, LaMont JT. Clostridium difficile infection. Annu Rev Med. 1998;49:375-90. [Medline].
- Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. N Engl J Med. Jan 27 1994;330(4):257-62. [Medline].
- Lyerly DM, Wilkins TD. Clostridium difficile. Infections of the Gastrointestinal Tract. 1995;867-891.
- McFarland LV, Mulligan ME, Kwok RY. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med. Jan 26 1989;320(4):204-10. [Medline].
- Starr J. Clostridium difficile associated diarrhoea: diagnosis and treatment. BMJ. Sep 3 2005;331(7515):498-501. [Medline].
Clostridium Difficile Colitis excerpt Article Last Updated: Aug 10, 2006
|
