Saturday, May 24, 2008

Clostridium Difficile (C. Diff)

Clostridium Difficile
From Wikipedia, the free encyclopedia

Clostridium difficile

C. difficile colonies on a blood agar plate.

Scientific classification
C. difficile
Binomial name
Clostridium difficileHall & O'Toole, 1935

Clostridium difficile (pronounced /klɒsˈtrɪdiəm dɪˈfɪsɪli/, also known as CDF/cdf', or 'C. diff') is a species of bacteria of the genus Clostridium which are Gram-positive, anaerobic, spore-forming rods (bacillus).[1] C. difficile is the most significant cause of Pseudomembranous colitis,[2] a severe infection of the Colon, often after normal gut flora is eradicated by the use of antibiotics. Treatment is by stopping any antibiotics and commencing specific anticlostridial antibiotics, e.g. metronidazole.

Clostridia are motile bacteria that are ubiquitous in nature and are especially prevalent in soil. Under the microscope after Gram staining, they appear as long drumsticks with a bulge located at their terminal ends. Clostridium difficile cells are Gram positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. When stressed the bacteria produce spores which tolerate the extreme conditions the active bacteria does not.

First described by Hall and O'Toole in 1935, "the difficult clostridium" was resistant to early attempts at isolation and grew very slowly in culture.[3]

C. difficile is a commensal bacterium of the human intestine in a minority of the population. Patients who have been staying long-term in a hospital or a nursing home have a higher likelihood of being colonized by this bacterium. In small numbers it does not result in disease of any significance. Antibiotics, especially those with a broad spectrum of activity, cause disruption of normal intestinal flora, leading to an overgrowth of C. difficile. This leads to Pseudomembranous colitis.

C. difficile is resistant to most antibiotics. It flourishes under these conditions. It is transmitted from person to person by the fecal-oral route. Because the organism forms heat-resistant spores, it can remain in the hospital or nursing home environment for long periods of time. It can be cultured from almost any surface in the hospital. Once spores are ingested, they pass through the stomach unscathed because of their acid-resistance. They change to their active form in the colon and multiply.

It has been observed that several disinfectants commonly used in hospitals may fail to kill the bacteria, and may actually promote spore formation. However, disinfectants containing bleach are effective in killing the organisms[4].

Pseudomembranous colitis caused by C. difficile is treated with specific antibiotics, for example, vancomycin, metronidazole, bacitracin or fusidic acid.

Pathogenic C. difficile strains produce various toxins. The most well-characterized are enterotoxin (toxin A) and cytotoxin (toxin B).[1] These two toxins are both responsible for the Diarrhea and Inflammation seen in infected patients, although their relative contributions have been debated by researchers. Another toxin, binary toxin, has also been described, but its role in disease is not yet fully understood.[5]

Role in disease
With the introduction of broad-spectrum antibiotics in the latter half of the twentieth century, antibiotic-associated diarrhea became more common. Pseudomembranous colitis was first described as a complication of C. difficile infection in 1978,[6] when a toxin was isolated from patients suffering from pseudomembranous colitis and Koch's postulates were met.

Clostridium difficile infection (CDI), can range in severity from asymptomatic to severe and life threatening, and many deaths have been reported, especially amongst the aged. People are most often infected in hospitals, nursing homes, or institutions, although C. difficile infection in the community, outpatient setting is increasing. Clostridium difficile associated diarrhea (aka CDAD) has been linked to use of broad-spectrum antibiotics such as cephalosporins and clindamycin, though the use of quinolones is now probably the most likely culprit, which are frequently used in hospital settings. Frequency and severity of C. difficile colitis remains high and seems to be associated with increased death rates. Immunocompromised status and delayed diagnosis appear to result in elevated risk of death. Early intervention and aggressive management are key factors to recovery.

The rate of Clostridium difficile acquisition is estimated to be 13 percent in patients with hospital stays of up to two weeks and 50 percent in those with hospital stays longer than four weeks.
Increasing rates of community-acquired Clostridium difficile-associated infection/disease (CDAD) has also been linked to the use of medication to suppress gastric acid production: H2-receptor antagonists increased the risk twofold, and proton pump inhibitors threefold, mainly in the elderly. It is presumed that increased gastric pH, (alkalinity), leads to decreased destruction of spores.[7]

Often clinicians begin treatment before results have come back based on clinical presentation to prevent complications. Knowledge of the local epidemiology of intestinal flora of a particular institution can guide therapy.

Symptoms and signs
In adults, a clinical prediction rule found the best signs are[8] :

  1. significant diarrhea ("new onset of > 3 partially formed or watery stools per 24 hour period")
  2. exposure of antibiotics
  3. abdominal pain
  4. foul stool odor

The presence of any one of these findings has a sensitivity of 86% and a specificity of 45%.[8] In this study of hospitalized patients with a prevalence of positive cytotoxin assays of 14%, the positive predictive value was 20% and the negative predictive value was 95%.

  • Cytotoxicity assay
    C. difficile toxin detection as cytopathic effect in cell culture, and neutralized with specific anti-sera is the practical gold standard for studies investigating new CDAD diagnostic techniques. Toxigenic culture, in which organisms are cultured on selective medium and tested for toxin production remains the gold standard and is the most sensitive and specific test, although it is slow and labour-intensive.[9]
  • Enzyme-linked immunoabsorbant assay (ELISA) for toxin
    Assessment of the A and B toxins by enzyme-linked immunoabsorbant assay (ELISA) for toxin A or B (or both) has:
  • sensitivity 63-99%
  • specificity 93-100%
  • At a prevalence of 15%, this leads to:
  • positive predictive value 73%
  • negative predictive value 96%
  • Experts recommend sending as many as three samples to rule-out disease if initial tests are negative. C. difficile toxin should clear from the stool of previously infected patients if treatment is effective.
    Unfortunately, many hospitals only test for the prevalent toxin A. Strains that express only the B toxin are now present in many hospitals and ordering both toxins should occur. Not testing for both may contribute to a delay in obtaining laboratory results, which is often the cause of prolonged illness and poor outcomes.
  • Other stool tests
    Stool leukocyte measurements and stool lactoferrin levels have also been proposed as diagnostic tests, but may have limited diagnostic accuracy.[10]
  • Computed tomography
    In a recent study, a patient who received a diagnosis of CDC on the basis of computed tomography (CT scan) had an 88% probability of testing positive on stool assay.[11] Wall thickening is the key CT finding in this disease. Once colon wall thickening is identified as being >4 mm, the best ancillary findings were:
  • pericolonic stranding
  • ascites
  • colon wall nodularity
  • The presence of wall thickness plus any one of these ancillary findings yields:
  • Using criteria of >=10 mm or a wall thickness of >4 mm and any of the more-specific findings does not add significantly to the diagnosis but gives equally satisfactory results. In this study with a prevalence of positive C. difficile toxin of 54%, the positive predictive value was 88%. Patients who have antibiotic-associated diarrhea who have CT findings diagnostic of CDC merit consideration for treatment on that basis. A weakness of this study was not using a gold standard cytotoxicity assay.
Many persons will also be asymptomatic and colonized with Clostridium difficile. Treatment in asymptomatic patients is controversial, also leading into the debate of clinical surveillance and how it intersects with public health policy.

It is possible that mild cases do not need treatment.[12]

Patients should be treated as soon as possible when the diagnosis of Clostridium difficile colitis (CDC) is made to avoid frank sepsis or bowel perforation.

Three antibiotics are effective against C. difficile.

  1. Metronidazole 500 mg orally three times daily is the drug of choice, because of lower price and comparable efficacy[13].
  2. Oral vancomycin 125 mg four times daily is second-line therapy, but is avoided due to theoretical concerns of converting intestinal flora into vancomycin resistant organisms. Vancomycin must be administered orally because IV administration does not achieve gut lumen minimum therapeutic concentration. However, it is used in the following cases:
    • severe C. difficile diarrhea[14] (the duration of diarrhea is reduced to 3 versus 4.6 days with metronidazole[citation needed]);
    • no response to oral metronidazole; the organism is resistant to metronidazole;
    • the patient is allergic to metronidazole;
    • the patient is either pregnant or younger than 10 years of age.
  3. The use of linezolid may be considered too.
It has been known that drugs traditionally used to stop diarrhea worsen the course of C. difficile-related pseudomembranous colitis. Loperamide, diphenoxylate and bismuth compounds are indeed contraindicated, because slowing of fecal transit time is thought to result in extended toxin-associated damage. Cholestyramine, a powder drink occasionally used to lower cholesterol, is effective in binding both Toxin A and B, and slows bowel motility and helps prevent dehydration.[15] The dosage can be 4 grams daily, to up to four doses a day: caution should be exercised to prevent constipation, or drug interactions, most notably the binding of drugs by cholestyramine, preventing their absorption. Powdered banana flakes given twice daily is an alternative to cholestyramine and allow for stool bulking. Treatment with probiotics ("good" intestinal flora) has also been shown effective. Provision of Saccharomyces boulardii (Florastor) or Lactobacillus acidophilus twice daily times 30 days along with antibiotics has been clinically shown to shorten the duration of diarrhoea. A last-resort treatment in immunosuppressed patients is intravenous immunoglobulin (IVIG).[15]

In those patients that develop systemic symptoms of CDC, colectomy may improve the outcome if performed before the need for vasopressors.

Fecal bacteriotherapy
Fecal bacteriotherapy, a procedure related to probiotic research, has been suggested as a potential cure for the disease. It involves infusion of bacterial flora acquired from the feces of a healthy donor in an attempt to reverse bacterial imbalance responsible for the recurring nature of the infection. It has a success rate of nearly 95% according to some sources.[16][17][18]

The evolution of protocols for patients with recurrent C. difficile diarrhea also present a challenge: there is no known proper length of time or universally accepted alternative drugs with which one should be treated. However, re-treatment with metronidazole or vancomycin at the previous dose for 10 to 14 days is generally successful. The addition of rifampin to vancomycin also has been effective. Prophylaxis with competing, nonpathogenic organisms such as Lactobacillus spp. or Saccharomyces boulardii has been found to be helpful in preventing relapse in small numbers of patients (see, for example, Florastor, or Lactinex). It is thought that these organisms, also known as probiotics, help to restore the natural flora in the gut and make patients more resistant to colonization by C. difficile.[citation needed]

The most effective method for preventing CDAD is proper antimicrobial prescribing. In the hospital setting, where CDAD is most common, nearly all patients who develop CDAD are exposed to antimicrobials. Although this sounds easy to do, approximately 50% of antimicrobial use is considered inappropriate. This is consistent whether in the hospital, clinic, community, or academic setting. Several studies have demonstrated a decrease in CDAD by limiting antibiotics most strongly associated with CDAD or by limiting unnecessary antimicrobial prescribing in general, both in outbreak and non-outbreak settings.

Infection control measures, such as wearing gloves when caring for patients with CDAD, have been proven to be effective at preventing CDAD. This works by limiting the spread of C. difficile in the hospital setting.

Treatment with various oral supplements containing live bacteria has been studied in efforts to prevent Clostridium difficile-associated infection/disease. A randomized controlled trial using a probiotic drink containing Lactobacillus casei, L bulgaricus, and Streptococcus thermophilus was reported to have some efficacy. This study was sponsored by the company that produces the drink studied [19]. Although intriguing, several other studies have been unable to demonstrate any benefit of oral supplements of similar bacteria at preventing CDAD.[citation needed] Of note, patients on the antibiotics most strongly associated with CDAD were excluded from this study. On the 29th January 2008 scientists revealed that they have found a vaccination to prevent Clostridium Difficle. They stated it will be released in about 3 years time

Notable outbreaks
On June 4, 2003, two outbreaks of a highly virulent strain of this bacterium were reported in Montreal, Quebec and Calgary, Alberta, in Canada. Sources put the death count as low as 36 and as high as 89, with approximately 1,400 cases in 2003 and within the first few months of 2004. C. difficile infections continued to be a problem in the Quebec health care system in late 2004. As of March 2005, it had spread into the Toronto, Ontario area, hospitalizing 10 people. One died while the others were being discharged.

A similar outbreak took place at Stoke Mandeville Hospital in the United Kingdom between 2003 and 2005. The local epidemiology of C. difficile may offer clues on how its spread may relate to the amount of time a patient spends in hospital and/or a rehabilitation center. It also samples institutions' ability to detect increased rates, and their capacity to respond with more aggressive hand washing campaigns, quarantine methods, and availability of yoghurt to patients at risk for infection.

It has been suggested that both the Canadian and English outbreaks were related to the seemingly more virulent Strain NAP1/027 of bacterium. This novel strain, also known as Quebec strain, has also been implicated in an epidemic at two Dutch hospitals (Harderwijk and Amersfoort, both 2005). A theory for explaining the increased virulence of 027 is that it is a hyperproducer of both toxin A and B, and that certain antibiotics may actually stimulate the bacteria to hyperproduce.

On December 2, 2005, The New England Journal of Medicine, in an article spearheaded by Drs. Vivian Loo, Louise Poirier, and Mark Miller, reported the emergence of a new, highly toxic strain of C. difficile, resistant to fluoroquinolone antibiotics, such as Cipro (ciprofloxacin) and Levaquin (levofloxacin), said to be causing geographically dispersed outbreaks in North America.[20] The Centers for Disease Control in Atlanta has also warned of the emergence of an epidemic strain with increased virulence, antibiotic resistance, or both.[21]

As one analyzes the pool of patients with the spores, many who are asymptomatic will pass the organism to individuals who are immunocompromised and hence, susceptible to increasing rates of diarrhea and poor outcome. It seems notable that the clusters described above represent a challenge to epidemiologists trying to understand how the illness spreads via the convergence of information technology with clinical surveillance.

On October 1, 2006, the bacteria was said to have killed at least 49 people at hospitals in Leicester, England over eight months, according to a National Health Service investigation. Another 29 similar cases were investigated by coroners.[22] A UK Department of Health memo leaked shortly afterwards revealed significant concern in government about the bacterium, described as being "endemic throughout the health service"[23]

On October 27, 2006, 9 deaths were attributed to the bacterium in Quebec, Canada.[24]
On November 18th, 2006, the bacteria was reported to have been responsible for 12 deaths in Quebec, Canada. This 12th reported death was only two days after the St. Hyacinthe's Honoré Mercier announced that the outbreak was under control. Thirty-one patients were diagnosed with Clostridium difficile and four (as of Sat. Nov 18th) were still under observation. Cleaning crews took measures in an attempt to clear the outbreak.[25]

On February 27, 2007, a new outbreak was identified at Trillium Health Centre in Mississauga Ontario, where 14 people were diagnosed with the bacteria. The bacteria was the same strain as the one in Quebec. Officials have not been able to determine if C. difficile was responsible for deaths of four patients over the prior two months.[26]

Between February and June 2007, three patients at Loughlinstown Hospital in Dublin, Ireland were found by the coroner to have died as a result of C.diff infection. In an inquest, the Coroner's Court found that the hospital had no designated infection control team or consultant microbiologist on staff. [27]

In October 2007, Maidstone and Tunbridge Wells NHS Trust was heavily criticized by the Healthcare Commission regarding its handling of a major outbreak of C. difficile in its hospitals in Kent from April 2004 to September 2006. In its report, the Commission estimated that about 90 patients "definitely or probably" died as a result of the infection. [28][29]

In November 2007, the 027 strain has spread into several hospitals in southern Finland, with ten deaths out of 115 infected patients reported on 2007-12-14. [30]

Sequencing the genome of the Quebec strain
On December 14, 2005, researchers at McGill University in Montreal, Quebec, led by Dr. Ken Dewar and Dr. Andre Dascal and in collaboration with province-organized NPO Genome Quebec's research facility, announced they had sequenced the genome of the highly virulent Quebec strain of C. difficile. This was accomplished by using ultra high-throughput sequencing technology. The tests involved doing 400,000 DNA parallel sequencing reactions which took the bacterium's genome apart and reassembled it so it could be studied.[20][31]

It is expected this will allow quicker detection of the disease and better treatment.

A practice has developed of pronouncing its specific name as [difisīl] as if it was French, although it was intended as Latin (neuter singular nominative case).


  1. ^ a b Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology, 4th ed., McGraw Hill, pp. 322-4. ISBN 0-8385-8529-9.
  2. ^ Pseudomembranous Colitis. eMedicine. WebMD (1 July 2005). Retrieved on 2007-01-11.
  3. ^ Hall I, O'Toole E (1935). "Intestinal flora in newborn infants with a description of a new pathogenic anaerobe, Bacillus difficilis". Am J Dis Child 49: 390.
  4. ^ "Cleaning agents 'make bug strong'", BBC News Online, 3 April 2006. Retrieved on 2007-01-11.
  5. ^ Barth H, Aktories K, Popoff M, Stiles B (2004). "Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteins". Microbiol Mol Biol Rev 68 (3): 373-402, table of contents. doi:10.1128/MMBR.68.3.373-402.2004. PMID 15353562.
  6. ^ Larson H, Price A, Honour P, Borriello S (1978). "Clostridium difficile and the aetiology of pseudomembranous colitis". Lancet 1 (8073): 1063-6. PMID 77366.
  7. ^ Dial S, Delaney J, Barkun A, Suissa S (2005). "Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease". JAMA 294 (23): 2989-95. PMID 16414946.
  8. ^ a b Katz DA, Lynch ME, Littenberg B (1996). "Clinical prediction rules to optimize cytotoxin testing for Clostridium difficile in hospitalized patients with diarrhea". Am. J. Med. 100 (5): 487–95. doi:10.1016/S0002-9343(95)00016-X . PMID 8644759.
  9. ^ Murray PR, Baron EJ, Pfaller EA, Tenover F, Yolken RH (editors) (2003). Manual of Clinical Microbiology, 8th ed, Washington DC: ASM Press. ISBN 1-55581-255-3.
  10. ^ Vaishnavi C, Bhasin D, Kochhar R, Singh K (2000). "Clostridium difficile toxin and faecal lactoferrin assays in adult patients". Microbes Infect 2 (15): 1827-30. doi:10.1016/S1286-4579(00)01343-5 . PMID 11165926.
  11. ^ Kirkpatrick ID, Greenberg HM (2001). "Evaluating the CT diagnosis of Clostridium difficile colitis: should CT guide therapy?". AJR. American journal of roentgenology 176 (3): 635–9. PMID 11222194.
  12. ^ Nelson R. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004610. PMID 17636768
  13. ^ Teasley DG, Gerding DN, Olson MM, Peterson LR, Gebhard RL, Schwartz MJ, Lee JT Jr. Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet. 1983 Nov 5;2(8358):1043-6. PMID 6138597
  14. ^ Zar FA, Bakkanagari SR, Moorthi KM, Davis MB (2007). "A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity". Clin. Infect. Dis. 45 (3): 302–7. doi:10.1086/519265. PMID 17599306.
  15. ^ a b Stroehlein J (2004). "Treatment of Clostridium difficile Infection". Curr Treat Options Gastroenterol 7 (3): 235-239. doi:10.1007/s11938-004-0044-y. PMID 15149585.
  16. ^ Schwan A, Sjölin S, Trottestam U, Aronsson B (1983). "Relapsing clostridium difficile enterocolitis cured by rectal infusion of homologous faeces.". Lancet 2 (8354): 845. PMID 6137662.
  17. ^ Paterson D, Iredell J, Whitby M (1994). "Putting back the bugs: bacterial treatment relieves chronic diarrhoea.". Med J Aust 160 (4): 232-3. PMID 8309401.
  18. ^ Borody T (2000). ""Flora Power"-- fecal bacteria cure chronic C. difficile diarrhea.". Am J Gastroenterol 95 (11): 3028-9. PMID 11095314.
  19. ^ Hickson M, D'Souza AL, Muthu N, et al (2007). "Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial". BMJ 335 (7610): 80. doi:10.1136/bmj.39231.599815.55. PMID 17604300.
  20. ^ a b Loo V, Poirier L, Miller M, Oughton M, Libman M, Michaud S, Bourgault A, Nguyen T, Frenette C, Kelly M, Vibien A, Brassard P, Fenn S, Dewar K, Hudson T, Horn R, René P, Monczak Y, Dascal A (2005). "A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality". N Engl J Med 353 (23): 2442-9. doi:10.1056/NEJMoa051639. PMID 16322602.
  21. ^ McDonald L (2005). "Clostridium difficile: responding to a new threat from an old enemy". Infect Control Hosp Epidemiol 26 (8): 672-5. doi:10.1086/502600. PMID 16156321.
  22. ^ Trust confirms 49 superbug deaths - BBC News
  23. ^ Nigel Hawkes (11th January 2007). Leaked memo reveals that targets to beat MRSA will not be met. The Times. Retrieved on 2007-01-11.
  24. ^ C. difficile blamed for 9 death in hospital near Montreal. cNews (11th January 200). Retrieved on 2007-01-11.
  25. ^ 12th person dies of C. difficile at Quebec hospital - CBC News
  26. ^ CTV Toronto - C. difficile outbreak linked to fatal strain - CTV News, Shows and Sports - Canadian Television
  27. ^ Irish Independent, Superbug in hospitals linked to four deaths, 10 October, 2007
  28. ^ Healthcare Commission press release: Healthcare watchdog finds significant failings in infection control at Maidstone and Tunbridge Wells NHS Trust, 11 October 2007
  29. ^ Daily Telegraph, Health Secretary intervenes in superbug row, 11 October 2007
  30. ^ Ärhäkkä suolistobakteeri on tappanut jo kymmenen potilasta - - Kotimaa
  31. ^ Scientists map C. difficile strain - Institute of Public Affairs, Montreal
Further reading
Dallal R, Harbrecht B, Boujoukas A, Sirio C, Farkas L, Lee K, Simmons R (2002). "Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications". Ann Surg 235 (3): 363-72. doi:10.1097/00000658-200203000-00008. PMID 11882758.
Martin S, Jung R (2005). Gastrointestinal infections and enterotoxigenic poisonings. In: Pharmacotherapy: A Pathophysiologic Approach (DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, editors)., 6th ed., McGraw-Hill, pp. 2042-2043. ISBN.
McDonald L, Killgore G, Thompson A, Owens R, Kazakova S, Sambol S, Johnson S, Gerding D (2005). "An epidemic, toxin gene-variant strain of Clostridium difficile". N Engl J Med 353 (23): 2433-41. doi:10.1056/NEJMoa051590. PMID 16322603.
Yamada T; Alpers DH (editors) (2003). Textbook of Gastroenterology, 4th ed., Lippincott Williams & Wilkins, pp. 1870-1875. ISBN 0-7817-2861-4.
van den Hof S, van der Kooi T, van den Berg R, Kuijper E, Notermans D (2006). "Clostridium difficile PCR ribotype 027 outbreaks in the Netherlands: recent surveillance data indicate that outbreaks are not easily controlled but interhospital transmission is limited". Euro Surveill 11 (1): E060126.2. PMID 16801713.
Sunenshine R, McDonald L (2006). "Clostridium difficile-associated disease: New challenges from an established pathogen". Cleveland Clinic J. Med. 73: 187.

See also

  1. Contamination control
  2. Nosocomial infection
External links

  1. Information from the UK Clostridium difficile Support Group (UK)
  2. Information from the Original Clostridium difficile Support Group (UK)
  3. "From hand to mouth" Article from The Economist discussing C. difficile (requires subscription)
  4. Pathema-Clostridium Resource
  5. US CDC Report on Severe Clostridium difficile--Associated Disease in Populations Previously at Low Risk--Four States, 2005
Retrieved from


Conditions diagnosed by stool test
Gram positive bacteria
Medically important anaerobes
Gut flora

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Colon (anatomy)
From Wikipedia, the free encyclopedia

Colon (anatomy)

Front of abdomen, showing surface markings for liver, stomach, and large intestine.
subject #249 1177

The colon is a storage tube for solid wastes. The main function of the colon appears to be extraction of water and salts from feces. In mammals, it consists of the ascending colon, transverse colon, the descending colon, and the sigmoid colon. The colon from cecum to the splenic flexure (the junction between the transverse and descending colon) is also known as the right colon. The remainder is known as the left colon.

The location of the parts of the colon are either in the abdominal cavity or behind it in the retroperitoneum. The colon in those areas is fixed in location.

Arterial supply to the colon comes from branches of the superior and inferior mesenteric arteries. Flow between these two systems communicates via a "marginal artery" that runs parallel to the colon for its entire length. Historically, it has been believed that the arc of Riolan, or the meandering mesenteric artery (of Moskowitz), is a variable vessel connecting the proximal SMA to the proximal IMA that can be extremely important if either vessel is occluded. However, recent studies conducted with improved imaging technology have questioned the actual existence of this vessel, with some experts calling for the abolition of the terms from future medical literature.

Venous drainage usually mirrors colonic arterial supply, with the inferior mesenteric vein draining into the splenic vein, and the superior mesenteric vein joining the splenic vein to form the portal vein that then enters the liver.

Lymphatic drainage from the entire colon and proximal two-thirds of the rectum is to the paraortic nodes that then drain into the cisterna chyli. The lymph from the remaining rectum and anus can either follow the same route, or drain to the internal illiac and superficial inguinal nodes. The dentate line only roughly marks this transition.

Ascending colon
The ascending colon, on the right side of the abdomen, is about 12.5 cm long. It is the part of the colon from the cecum to the hepatic flexure (the turn of the colon by the liver). It is retroperitoneal in most humans. In ruminant grazing animals the cecum empties into the spiral colon. Anteriorly it is related to the coils of small intestine, the right edge of the greater omentum, and the anterior abdominal wall. Posteriorly, it is related to the iliacus, the iliolumbar ligament, the quadratus lumborum, the transverse abdominis, the diaphragm at the tip of the last rib; the lateral cutaneous, ilioinguinal, and iliohypogastric nerves; the iliac branches of the iliolumbar vessels, the fourth lumbar artery, and the right kidney.

The ascending colon is supplied by parasympathetic fibers of the vagus nerve (CN X).

Arterial supply of the ascending colon comes from the ileocolic artery and right colic artery, both branches of the SMA. While the ileocolic artery is almost always present, the right colic can be absent in 5-15% of individuals.

Transverse colon
The transverse colon is the part of the colon from the hepatic flexure (the turn of the colon by the liver) to the splenic flexure (the turn of the colon by the spleen). The transverse colon hangs off the Stomach, attached to it by a wide band of tissue called the greater omentum. On the posterior side, the transverse colon is connected to the posterior abdominal wall by a mesentery known as the transverse mesocolon.

The transverse colon is encased in peritoneum, and is therefore mobile (unlike the parts of the colon immediately before and after it). More cancers form as the large intestine goes along and the contents become more solid (water is removed) in order to form feces.

The proximal two-thirds of the transverse colon is perfused by the middle colic artery, a branch of superior mesenteric artery, while the latter third is supplied by branches of the inferior mesenteric artery. The "watershed" area between these two blood supplies, which represents the embryologic division between the midgut and hindgut, is an area sensitive to ischemia.

Descending colon
The descending colon is the part of the colon from the splenic flexure to the beginning of the sigmoid colon. It is retroperitoneal in two-thirds of humans. In the other third, it has a (usually short) mesentery. Arterial supply comes via the left colic artery.

Sigmoid colon

Diagram of the Human Intestine.

The sigmoid colon is the part of the large intestine after the descending colon and before the rectum. The name sigmoid means S-shaped. The walls of the sigmoid colon are muscular, and contract to increase the pressure inside the colon, causing the stool to move into the rectum.

The sigmoid colon is supplied with blood from several branches (usually between 2 and 6) of the sigmoid arteries, a branch of the IMA. The IMA terminates as the superior rectal artery.
Sigmoidoscopy is a common diagnostic technique used to examine the sigmoid colon.

Redundant colon
One variation on the normal anatomy of the colon occurs when extra loops form, resulting in a longer than normal organ. This condition, referred to as redundant colon, typically has no direct major health consequences, though rarely volvulus occurs resulting in obstruction and requiring immediate medical attention.[1] A significant indirect health consequence is that use of a standard adult colonoscope is difficult and in some cases impossible when a redundant colon is present, though specialized variants on the instrument (including the pediatric variant) are useful in overcoming this problem.[2]

The large intestine comes after the small intestine in the digestive tract and measures approximately 1.5 meters in length. Although there are differences in the large intestine between different organisms, the large intestine is mainly responsible for storing waste, reclaiming water, maintaining the water balance, and absorbing some vitamins, such as vitamin K.

By the time the chyme has reached this tube, almost all nutrients and 90% of the water have been absorbed by the body. At this point some electrolytes like sodium, magnesium, and chloride are left as well as indigestible carbohydrates known as dietary fiber. As the chyme moves through the large intestine, most of the remaining water is removed, while the chyme is mixed with mucus and bacteria known as gut flora, and becomes feces. The bacteria break down some of the fiber for their own nourishment and create acetate, propionate, and butyrate as waste products, which in turn are used by the cell lining of the colon for nourishment. This is an example of a symbiotic relationship and provides about one hundred calories a day to the body. The large intestine produces no digestive enzymeschemical digestion is completed in the small intestine before the chyme reaches the large intestine. The pH in the colon varies between 5.5 and 7 (slightly acidic to neutral).

There are a number of diseases or disorders of the colon:

  1. Angiodysplasia of the colon
  2. Chronic functional abdominal pain
  3. Colitis
  4. Colorectal Cancer (Colon Cancer)
  5. Constipation
  6. Crohn's Disease
  7. Diarrhea
  8. Diverticulitis
  9. Diverticulosis
  10. Hirschsprung's Disease (Megacolon) (aganglionosis)
  11. Intussusception
  12. Irritable Bowel Syndrome (IBS)
  13. Polyposis (see also Colorectal polyp)
  14. Pseudomembranous colitis
  15. Ulcerative Colitis and
  16. toxic megacolon


  1. ^ Mayo Clinic Staff (2006-10-13). Redundant colon: A health concern?. Ask a Digestive System Specialist. Retrieved on 2007-06-11.
  2. ^ Lichtenstein, Gary R.; Peter D. Park, William B. Long, Gregory G. Ginsberg, Michael L. Kochman (18 August 1998). "Use of a Push Enteroscope Improves Ability to Perform Total Colonoscopy in Previously Unsuccessful Attempts at Colonoscopy in Adult Patients". The American Journal of Gastroenterology 94 (1): 187. PMID 9934753. Retrieved on 2007-06 12. Note: Single use PDF copy provided free by Blackwell Publishing for purposes of Wikipedia content enrichment.
Additional images


1. Ascending colon
2. Transverse Colon
3. Descending Colon
4. Sigmoid Colon
5. Rectum

External links

  1. Overview and diagrams at
  2. 09-118h. at Merck Manual of Diagnosis and Therapy Home Edition
  3. MeSH Large+Intestine
  4. Virtual Slidebox at Univ. Iowa Slide 393
  5. SUNY Labs 37:13-0100 - "Abdominal Cavity: The Colon and its Divisions"
  6. Video: What is Colorectal Cancer?

vdeAnatomy of torso, digestive system: Gastrointestinal tract
Upper GI: to stomach
MouthPharynx (nasopharynx, oropharynx, hypopharynx) • EsophagusCrop
Upper GI: stomach
rugae - gastric pits - cardia/gland - fundus/gland - pylorus/gland - pyloric antrum - pyloric canal - greater curvature - lesser curvature - angular incisure
Lower GI: intestines
Small intestine: Duodenum (Suspensory muscle, Major duodenal papilla, Minor duodenal papilla) • Duodenojejunal flexureJejunumIleum • continuous (intestinal villus, crypts of Lieberkühn, circular folds)
Junction: Vermiform appendixIleocecal valveLarge intestine: Cecum • Colon (ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, sigmoid colon) • continuous (taenia coli, haustra, epiploic appendix)
Lower GI: termination
Rectum: Houston valverectal ampullapectinate line
Anal canal: anal valvesanal sinusesanal columnsHilton's white lineAnus: Sphincter ani internus muscleSphincter ani externus muscle
Lower GI: lymph
GALT: Peyer's patches (M cells)
Retrieved from ""
Categories: Abdomen Digestive system

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Pseudomembranous colitis

Pseudomembranous colitis
From Wikipedia, the free encyclopedia

Classification and external resources

See also: Clostridium Difficile

Pseudomembranous colitis is an infection of the Colon often, but not always, caused by the bacterium Clostridium difficile. Still, the expression "C. diff colitis" is used almost interchangeably with the more proper term of pseudomembranous colitis. The illness is characterized by offensive-smelling Diarrhea , fever, and abdominal pain. It can be severe, causing toxic megacolon, or even fatal.

Mechanism of Disease
The use of broad-spectrum antibiotics such as clindamycin and cephalosporins causes the normal bacterial flora of the bowel to be altered. In particular, when the antibiotic kills off other, competing bacteria in the intestine, any bacteria remaining will have less competition for space and nutrients there. The net effect is to permit much more extensive growth than normal of certain bacteria. Clostridium difficile is one such type of bacterium. In addition to proliferating in the bowel, the C. diff also elaborates a toxin. It is this toxin that is responsible for the diarrhea which characterizes pseudomembranous colitis.

Risk factors and epidemiology
In most cases a patient presenting with pseudomembranous colitis has recently been on antibiotics. Antibiotics disturb the normal bowel bacterial flora. Clindamycin is the antibiotic classically associated with this disorder, but any antibiotic can cause the condition. Even though they are not particularly likely to cause pseudomembranous colitis, due to their very frequent use cephalosporin antibiotics (such as cefazolin and cephalexin) account for a large percentage of cases. Diabetics and the elderly are also at increased risk, although half of cases are not associated with risk factors.

Other risk factors include increasing age and recent major surgery. There is some evidence that proton pump inhibitors are a risk factor for pseudomembranous colitis,[1] but others question whether this is a false association or statistical artifact (increased PPI use is itself a marker of increased age and co-morbid illness).[2]; indeed, one large case-controlled study showed that PPI's are not a risk factor.[3] Recently, evidence has emerged to suggest that the use of ciprofloxacin (in addition to a primary causative antibiotic such as clindamycin) is associated with increased mortality in patients with pseudomembranous colitis.)[4]

Clinical Features
As noted above, pseudomembranous colitis is characterized by diarrhea, abdominal pain, and fever. Usually, the diarrhea is non-bloody, although blood may be present if the affected individual is taking blood thinners or has an underlying lower bowel condition such as hemorrhoids. Abdominal pain is almost always present and may be severe. So-called "peritoneal" signs (e.g. rebound tenderness) may be present. "Constitutional" signs such as fever, fatigue, and loss of appetite are prominent. In fact, one of the main ways of distinguishing pseudomembranous colitis from other antibiotic-associated diarrheal states is that patients with the former are sick. That is, they are often prostrate, lethargic, and generally look unwell. Their "sick" appearance tends to be paralleled by the results of their blood tests which often show anemia, an elevated white blood cell count, and low serum albumin.

In order to make the diagnosis, it is, of course, essential that the treating physician be aware of any recent antibiotic usage. The disease may occur as late as one or two months after the use of antibiotics. Although there is some relationship between dose/duration of antibiotic and likelihood of developing pseudomembranous colitis, it may occur even after a single dose of antibiotic. In fact, the use of single-dose antibiotic is a common practice in surgical patients for whom such a treatment is often given just prior to surgery in order to prevent infection at the surgical site. Hence, even though unlikely to cause pseudomembranous colitis on a per-case basis, single-dose antibiotic treatment, by virtue of the large number of patients receiving such, is an important cause of pseudomembranous colitis.

Prior to the advent of tests to detect the Clostridium difficile toxin, the diagnosis was most often made by colonoscopy or sigmoidoscopy. The appearance of "pseudomembranes" on the surface of the colon or rectum is diagnostic of the condition. The pseudomembranes are composed of inflammatory debris, white blood cells, etc.

Although colonoscopy and sigmoidoscopy are still employed, stool testing for the presence of Clostridium difficile toxin is now often the first-line diagnostic approach. Usually, only two toxins are tested for - Toxin A and Toxin B - but the organism produces at least several others. It is, perhaps, for this reason that some people who seem to have pseudomembranous colitis (i.e. a history of antibiotic use, non-bloody diarrhea, and the presence of pseudomembranes seen on colonoscopy) do not have detectable C. diff toxin in their stool.

The disease is usually treated with metronidazole (400 mg every 8 hours). Oral vancomycin (125 mg every 6 hours) is an alternative but, due to its cost, is often reserved for those patients who have experienced a relapse after a course of metronidazole (a common outcome). Vancomycin treatment also presents the risk of the development of vancomycin-resistant enterococcus, and its use for the treatment of C. difficile infection is now questioned by some institutions. Occasionally metronidazole has been associated with the development of pseudomembranous colitis. In these cases metronidazole is still an effective treatment, since the cause of the colitis is not the antibiotic, but rather the change in bacterial flora from a previous round of antibiotics.

Adjunctive therapy may include cholestyramine, a bile acid resin that can be used to bind C. difficile toxin.

Saccharomyces boulardii (a yeast) has been shown in one small study of 124 patients to reduce the recurrence rate of pseudomembranous colitis.[5] A number of mechanisms have been proposed to explain this effect.

Fecal bacteriotherapy, a procedure related to probiotic research, has been suggested as an alternative cure for the disease. It involves infusion of bacterial flora acquired from the feces of a healthy donor in an attempt to repair the bacterial imbalance responsible for the recurring nature of the infection. A very high success rate of nearly 95% makes it an effective "last resort" therapy for antibiotic resistant as well as recurring C. difficile infections.

Anecdotal evidence suggests kefir can help treat pseudomembranous colitis.

If antibiotics do not control the infection the patient may require a colectomy (removal of the colon) for treatment of the colitis.

A randomized controlled trial using a probiotic drink containing Lactobacillus casei, L bulgaricus, and Streptococcus thermophilus was reported to have some efficacy. This study was sponsored by the company that produces the drink studied [6]. Although intriguing, several other studies have been unable to demonstrate any benefit of oral supplements of similar bacteria at preventing CDAD.[citation needed]

  1. ^ Dial S, Delaney C, Schneider V, Suissa S. (2006). "Proton pump inhibitor use and risk of community-acquired Clostridium difficile-associated disease defined by prescription for oral vancomycin therapy". CMAJ 175 (7): 745–48. doi:10.1503/cmaj.060284.
  2. ^ Pépin J, Saheb N, Coulombe M, et al. (2005). "Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile associated diarrhea: a cohort study during an epidemic in Quebec". Clin Infect Dis 41: 1254–60. doi:10.1086/496986. PMID 16206099.
  3. ^ Lowe DO, Mamdani MM, Kopp A, Low DE, Juurlink DN (2006). "Proton pump inhibitors and hospitalization for Clostridium difficile-associated disease: a population-based study". Clin Infect Dis 43 (10): 1272–6. doi:10.1086/508453. PMID 17051491.
  4. ^ Pépin J, Saheb N, Coulombe M, et al. (2005). "Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile associated diarrhea: a cohort study during an epidemic in Quebec". Clin Infect Dis 41: 1254–60. doi:10.1086/496986. PMID 16206099.
  5. ^ McFarland LV, Surawicz CM, Greenberg RN, et al. (1994). "A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease". JAMA 271 (24): 1913–18. doi:10.1001/jama.271.24.1913. PMID 8201735.
  6. ^ Hickson M, D'Souza AL, Muthu N, et al (2007). "Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial". BMJ 335 (7610): 80. doi:10.1136/bmj.39231.599815.55. PMID 17604300.
External links

PWA Health Group - Saccharomyces boulardii Info Sheet
Video depicting the colonoscopy of a colon with Pseudomembranous colitis

vdeBacterial diseases (primarily A00-A79, 001-041,080-109)
Clostridium (Pseudomembranous colitis, Botulism, Tetanus, Gas gangrene) - Streptococcus A and B (Scarlet fever, Erysipelas) - Staphylococcus (Toxic shock syndrome) - Bacilli (Anthrax, Listeriosis)
Mycobacterium: Tuberculosis (Ghon focus, Ghon's complex, Tuberculous meningitis, Pott's disease, Rich focus, Scrofula, Bazin disease, Lupus vulgaris, Miliary tuberculosis) - Leprosy - Lady Windermere syndrome - Buruli ulcer -Actinomycetales: Actinomycosis - Nocardiosis - Diphtheria - Erythrasma
Syphilis (Bejel) - Yaws - Pinta - Relapsing fever - Noma - Trench mouth - Lyme disease - Rat-bite fever (Sodoku) - Leptospirosis
Chlamydophila (Psittacosis) - Chlamydia (Chlamydia, Lymphogranuloma venereum, Trachoma)
Rickettsioses (Typhus, Scrub typhus, Rocky Mountain spotted fever, Boutonneuse fever, Q fever, Trench fever, Rickettsialpox) - Brucellosis - Cat scratch feverBartonellosis (Bacillary angiomatosis)
G-/β&γ Proteobacteria
Salmonella (Typhoid fever, Paratyphoid fever, Salmonellosis) - other intestinal (Cholera, Shigellosis) - Zoonotic (Bubonic plague, Tularemia, Glanders, Melioidosis, Pasteurellosis) - Other: Pertussis - Meningococcus (Meningococcal disease, Waterhouse-Friderichsen syndrome) - Legionellosis - Brazilian purpuric fever - Chancroid - Donovanosis - Gonorrhea

vdeDigestive system - Gastroenterology (primarily K20-K93, 530-579)
Esophagitis - GERD - Achalasia - Boerhaave syndrome - Nutcracker esophagus - Zenker's diverticulum - Mallory-Weiss syndrome - Barrett's esophagus
Peptic (gastric/duodenal) ulcer - Gastritis - Gastroenteritis - Duodenitis - Dyspepsia - Pyloric stenosis - Achlorhydria - Gastroparesis - Gastroptosis - Portal hypertensive gastropathy
Inguinal (Indirect, Direct) - Femoral - Umbilical - Incisional - Diaphragmatic - Hiatus
Noninfectiveenteritis & colitis
Inflammatory bowel disease (IBD, Crohn's disease, Ulcerative colitis) - noninfective gastroenteritis
Other intestinal
vascular (Abdominal angina, Mesenteric ischemia, Ischemic colitis, Angiodysplasia) - Ileus/Bowel obstruction (Intussusception, Volvulus) - Diverticulitis/Diverticulosis - Irritable bowel syndrome (IBS)other functional intestinal disorders (Constipation, Diarrhea, Megacolon/Toxic megacolon, Proctalgia fugax) - Anal fissure/Anal fistula - Anal abscess - Rectal prolapse - Proctitis (Radiation proctitis)
Alcoholic liver disease - Liver failure (Acute liver failure) - Cirrhosis - PBC - Autoimmune hepatitis - NASH - Fatty liver - Peliosis hepatis - Hepatic veno-occlusive disease - Portal hypertension - Hepatorenal syndrome

Gallbladder (Gallstones, Choledocholithiasis, Cholecystitis, Cholesterolosis, Rokitansky-Aschoff sinuses)
Biliary tree (Cholangitis, Cholestasis/Mirizzi's syndrome, PSC, Biliary fistula, Ascending cholangitis)Pancreas (Acute pancreatitis, Chronic pancreatitis, Pancreatic pseudocyst, Hereditary pancreatitis)

Appendicitis - Peritonitis (Spontaneous bacterial peritonitis)
Malabsorption (celiac, Tropical sprue, Blind loop syndrome, Whipple's)

postprocedural: Gastric dumping syndrome - Postcholecystectomy syndromebleeding: Hematemesis - Melena - Gastrointestinal bleeding (Upper, Lower)
See also congenital

Retrieved from ""
Categories: Gastroenterology Bacterial diseases Conditions diagnosed by stool test

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