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__NOTOC__
__NOTOC__
{{DiseaseDisorder infobox |
{{Infobox disease|
  Name          = Pseudomembranous colitis |
|  Name          = Pseudomembranous colitis  
  ICD10          = {{ICD10|A|04|7|a|00}} |  
| ICD10          = {{ICD10|A|04|7|a|00}}  
  ICD9          = {{ICD9|008.45}} |
| ICD9          = {{ICD9|008.45}}  
  ICDO          = |
| ICDO          =  
  Image          = |
| Image          = Colonic pseudomembranes low mag.jpg
  Caption        = |
| Caption        = [[Micrograph]] of a [[colon (anatomy)|colonic]] pseudomembrane in ''[[Clostridium difficile]]'' colitis, a type of '''pseudomembranous colitis'''.
  OMIM          = |
|  OMIM          =  
  MedlinePlus    = 000259 |
| MedlinePlus    = 000259  
  DiseasesDB    = 2820 |
|  eMedicineSubj  = med
  MeshID        = D004761 |
| eMedicineTopic = 1942
|  DiseasesDB    = 2820  
| MeshID        = D004761  
}}
}}
{{SI}}
{{SI}}
{{Main|Clostridium difficile infection}}
'''''For patient information, click [[Pseudomembranous colitis (patient information)|here]].'''''
{{SK}} antibiotic-associated enterocolitis
{{CMG}}
{{CMG}}


==Overview==
==Overview==


'''Pseudomembranous colitis''' is an infection of the [[colon (anatomy)|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.
'''Pseudomembranous enterocolitis''' is an acute inflammation of the intestinal mucosa that is characterized by the presence of pseudomembranes or plaques in the small intestine ('''pseudomembranous enteritis''') and the large intestine ('''pseudomembranous colitis'''). It is commonly associated with antibiotic therapy. Pathogens that have been implicated to cause pseudomembranous enterocolitis include ''[[Clostridium difficile]]'', ''[[Clostridium perfringens]]'', ''[[Staphylococcus aureus]]'', ''[[Klebsiella oxytoca]]'', [[Salmonella|''Salmonella'' species]], and [[Candida|''Candida'' species]].  
 
The illness is features by offensive-smelling [[diarrhea]], [[fever]], and [[abdominal pain]]. In severe cases, life-threatening complications can develop, such as [[toxic megacolon]].
 
==Pathophysiology==


==Mechanism of Disease==
The use of systemic antibiotics, including (but not limited to) any penicillin-based antibiotic such as [[amoxicillin]], [[cephalosporin]]s, and [[clindamycin]], 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. The net effect is to permit more extensive growth than normal of certain bacteria. ''Clostridium difficile'' is one such type of bacterium. In addition to proliferating in the bowel, ''C. difficile'' also produces [[toxins]]. Without either toxin A or toxin B, ''C. difficile'' may colonize the gut, but is unlikely to cause pseudomembranous colitis.<ref>{{cite journal | title=The role of toxin A and toxin B in''Clostridium difficile'' infection | author= Sarah A. Kuehne, Stephen T. Cartman, John T. Heap, Michelle L. Kelly, Alan Cockayne & Nigel P. Minton | journal=[[Nature (journal)|Nature]] | year=2010 |doi=10.1038/nature09397 | pmid=20844489 | volume=467 | issue=7316 | pages=711–3}}</ref>
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 bacteria. 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==
==Causes==
In most cases a patient presenting with pseudomembranous colitis has recently been on [[antibiotic]]s.  Antibiotics disturb the normal bowel bacterial [[Flora (microbiology)|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, but, rather, 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.
===Causes by Organ System===
{|style="width:80%; height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" |'''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" | No underlying causes
|-
|bgcolor="LightSteelBlue"| '''Chemical/Poisoning'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Dental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Dermatologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
|bgcolor="Beige"| [[Amoxicillin]], [[Aztreonam]], [[Cefadroxil]], [[Cefditoren]], [[Ceftazidime]], [[Cefoxitin sodium]], [[Cytarabine]], [[Cefaclor]], [[Doxorubicin Hydrochloride]], [[Imipenem-Cilastatin]], [[Lincomycin Hydrochloride]],  [[Lomefloxacin hydrochloride]], [[Oxacillin]], [[Trovafloxacin mesylate]]
|-
|-bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Endocrine'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Environmental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Genetic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Hematologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Iatrogenic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Infectious Disease'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Musculoskeletal/Orthopedic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Neurologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Nutritional/Metabolic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Oncologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Ophthalmologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Overdose/Toxicity'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Psychiatric'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Pulmonary'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Renal/Electrolyte'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Rheumatology/Immunology/Allergy'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Sexual'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Trauma'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Urologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Miscellaneous'''
|bgcolor="Beige"| No underlying causes
|-
|}


Other risk factors include increasing age and recent major surgery.  There is some evidence that [[proton pump inhibitor]]s are a risk factor for pseudomembranous colitis,<ref>{{cite journal | title=Proton pump inhibitor use and risk of community-acquired ''Clostridium difficile''-associated disease defined by prescription for oral vancomycin therapy | author=Dial S, Delaney C, Schneider V, Suissa S. | journal=CMAJ | year=2006 | volume=175 | issue=7 | pages=745&ndash;48 | doi=10.1503/cmaj.060284
===Causes in Alphabetical Order===
}}</ref> 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).<ref>{{cite journal | author=Pépin J, Saheb N, Coulombe M, ''et al.'' | title=Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile associated diarrhea: a cohort study during an epidemic in Quebec | journal=Clin Infect Dis | year=2005 | volume=41 | pages=1254&ndash;60 | DOI=10.1086/496986 | id=PMID 16206099
{{col-begin|width=80%}}
}}</ref>; indeed, one large case-controlled study showed that PPI's are not a risk factor.<ref>{{cite journal | author=Lowe DO, Mamdani MM, Kopp A, Low DE, Juurlink DN | title=Proton pump inhibitors and hospitalization for ''Clostridium difficile''-associated disease: a population-based study | journal=Clin Infect Dis | year=2006 | volume=43 | issue=10 | pages=1272&ndash;6 | id=PMID 17051491 }}</ref> 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.
{{col-break|width=33%}}
*[[Amoxicillin]]
*[[Aztreonam]]
*[[Cefadroxil]]
*[[Ceftazidime]]
*[[Cytarabine]]
*[[Doxorubicin Hydrochloride]]
* [[Lomefloxacin hydrochloride]]
*[[Trovafloxacin mesylate]]


==Clinical Features==
{{col-break|width=33%}}
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]].


==Diagnosis==
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 (anatomy)|colon]] or [[rectum]] is diagnostic of the condition. The pseudomembranes are composed of inflammatory debris, white blood cells, etc.
{{col-break|width=33%}}


Although colonoscopy and sigmoidoscopy are still employed, stool testing for the presence of Clostridium difficile toxin is now often the first-line diagnostic appraoach. 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.
{{col-end}}


===X-ray===
==Epidemiology==


* Plain radiographic findings in including colonic ileus, small bowel ileus, ascites, and nodular haustral thickening .
In most cases, a patient presenting with pseudomembranous colitis has recently been on [[antibiotic]]s. Antibiotics disturb the normal bowel bacterial flora.  Certain antibiotics, such as [[ampicillin]],<ref>{{cite book|last=Katzung|first=Bertram G.|title=Basic and Clinical Pharmacology|year=2007|publisher=McGraw Hill Medical|location=New York, NY |isbn=978-0-07-145153-6|pages=733}}</ref> have a higher propensity to create an environment where the bacteria causing pseudomembranous colitis can outcompete the normal gut [[Flora (microbiology)|flora]]. [[Clindamycin]] is the antibiotic classically associated with this disorder, but any antibiotic can cause the condition.  Though they are not particularly likely to cause pseudomembranous colitis, [[cephalosporin]] antibiotics (such as [[cefazolin]] and [[cephalexin]]) account for a large percentage of cases due to their very frequent use. Diabetics and the elderly are also at increased risk, although half of cases are not associated with risk factors.
* [[Thumbprinting]] (unusual, wide transverse bands associated with thickening of the haustral folds) and gaseous distention of the colon have also been identified.


===CT===
Other risk factors include increasing age and recent major surgery.  Some evidence shows [[proton pump inhibitor]]s are a risk factor for ''C. difficile'' infection and pseudomembranous colitis,<ref>{{cite journal |author=Deshpande A |title=Association between Proton Pump Inhibitor therapy and Clostridium difficile infection in a Meta-Analysis |journal=Clin. Gastroenterol. Hepatol.|year=2011 |pmid=22019794  |url=http://www.sciencedirect.com/science/article/pii/S1542356511010780|author-separator=, |author2=Pant C |author3=Pasupuleti V |display-authors=3.|doi=10.1016/j.cgh.2011.09.030 |last4=Rolston |first4=David D.K. |last5=Jain |first5=Anil |last6=Deshpande |first6=Narayan |last7=Thota |first7=Priyaleela |last8=Sferra |first8=Thomas J. |last9=Hernandez |first9=Adrian V. |volume=10 |issue=3 |pages=225–33}}</ref><ref>{{cite journal | title=Proton pump inhibitor use and risk of community-acquired ''Clostridium difficile''-associated disease defined by prescription for oral vancomycin therapy | author=Dial S, Delaney C, Schneider V, Suissa S. | journal=[[Canadian Medical Association Journal|CMAJ]] | year=2006 | volume=175 | issue=7 | pages=745&ndash;48 |doi=10.1503/cmaj.060284 | pmid=17001054 | pmc=1569908
}}</ref> 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).<ref>{{cite journal | author=Pépin J, Saheb N, Coulombe M, ''et al.'' | title=Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile associated diarrhea: a cohort study during an epidemic in Quebec |journal=[[Clinical Infectious Diseases|Clin Infect Dis]] | year=2005 | volume=41 | pages=1254&ndash;60
| doi=10.1086/496986 | pmid=16206099 | issue=9
}}</ref> Indeed, one large [[case-control study]] showed PPIs are not a risk factor.<ref>{{cite journal | author=Lowe DO, Mamdani MM, Kopp A, Low DE, Juurlink DN | title=Proton pump inhibitors and hospitalization for ''Clostridium difficile''-associated disease: a population-based study |journal=Clin Infect Dis | year=2006 | volume=43 | issue=10 | pages=1272&ndash;6 | pmid=17051491  |doi=10.1086/508453}}</ref>


* Common CT findings include wall thickening, low-attenuation mural thickening corresponding to mucosal and submucosal edema, the accordion sign, the target sign, double halo sign, pericolonic stranding, and ascites.
==Signs and Symptoms==


** The target sign, which consists of two or three concentric rings of different attenuation, indicates mucosal hyperemia and submucosal edema or inflammation. The rings of varying attenuation are best appreciated during the arterial phase of enhancement.
As noted above, pseudomembranous colitis is characterized by diarrhea, abdominal pain, and fever. Usually, the diarrhea is not bloody, although blood may be present if the affected individual is taking blood thinners or has an underlying lower bowel condition, such as inflamed 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 in general 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]].
** The accordion sign is seen when orally administered contrast material becomes trapped between markedly thickened haustral folds, giving the appearance of alternating bands of high attenuation (contrast material) and low attenuation (edematous haustra). This sign is highly suggestive of PMC, although it is usually seen only in advanced cases.


<gallery>
Image:


Pseudomembranous-colitis-001.jpg
==Diagnosis==


Image:
{| align=right
| [[File:Pseudomembranoese Colitis coronar.jpg|200px|thumb|Pseudomembranous colitis in computertomography]]
|-
| [[File:PMC 1.jpg|thumb|200px|right|[[colonoscopy|Endoscopic]] image of pseudomembranous colitis, with yellow pseudomembranes seen on the wall of the [[sigmoid colon]]]]
|-
| [[Image:Pseudomembranous colitis.JPG|thumb|200px|Pathological specimen showing pseudomembranous colitis]]
|}


Pseudomembranous-colitis-002.jpg
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 six months after antibiotic use. Although some relationship between dose/duration of antibiotic and the likelihood of developing pseudomembranous colitis occurs, it may occur even after a single dose of antibiotic. In fact, the use of a single-dose prophylactic antibiotic is a common practice in surgical and dental patients to prevent infections associated with a procedure. Hence, 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. Use of proton pump inhibitor drugs, such as omeprazole for gastric reflux, or some forms of asthma inhaler, or all drugs with anticholinergic effects that slow the digestive transit time lead to retention of toxins and exacerbate the effects of broad-spectrum antibiotics.


Image:
Prior to the advent of tests to detect ''C. difficile'' toxins, the diagnosis was most often made by [[colonoscopy]] or [[sigmoidoscopy]]. The appearance of "pseudomembranes" on the mucosa of the [[Colon (anatomy)|colon]] or [[rectum]] is diagnostic of the condition. The pseudomembranes are composed of an exudate made of inflammatory debris, white blood cells, etc.


Pseudomembranous-colitis-003.jpg
Although colonoscopy and sigmoidoscopy are still employed, stool testing for the presence of ''C. difficile'' toxins is now often the first-line diagnostic approach. Usually, only two toxins are tested for - toxin A and toxin B - but the organism produces several others. This test is not 100% accurate, with a considerable false-negative rate even with repeat testing.


</gallery>
Another, more recent two-step approach involves testing for the presence of ''C. difficile'' in the stool and then testing for toxin production. The first step is performed by testing for the presence of the ''C. difficile'' GDH antigen. If the first step is positive, a second test, a PCR assay targeting the toxin genes, is performed.
 
==Prevention==
 
A [[randomized controlled trial]] using a [[probiotic]] drink containing ''[[Lactobacillus casei]]'', ''[[Lactobacillus bulgaricus|L. bulgaricus]]'', and ''[[Streptococcus thermophilus]]'' was reported to have some efficacy. This study was, however, sponsored by the company that produces the drink.<ref name="pmid17604300">{{cite journal |author=Hickson M, D'Souza AL, Muthu N, ''et al.'' |title=Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial|journal=[[BMJ]] |volume=335 |issue=7610 |pages=80 |year=2007 |pmid=17604300|doi=10.1136/bmj.39231.599815.55 |pmc=1914504}}</ref> Although intriguing, several other studies have been unable to demonstrate any benefit of oral supplements of similar bacteria at preventing ''C. difficile''-associated diarrhea.


==Treatment==
==Treatment==
The disease is usually treated with [[metronidazole]] (400 mg every 8 hours).  Oral [[vancomycin]] (125 mg every 6 hourly) 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.
The disease is usually treated with either [[metronidazole]] or oral [[vancomycin]]. Oral metronidazole at doses of 500 mg three times a day for 10 to 14 days can be used for mild to moderate cases of ''C. difficile''.  Choice of drug depends on severity of disease and the ability to tolerate and absorb oral medications. Vancomycin treatment does present the risk of the development of [[vancomycin-resistant enterococcus|vancomycin-resistant ''Enterococcus'']], though it is only minimally absorbed into the bloodstream from the gastrointestinal tract. Metronidazole itself has on occasion 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. ''C. difficile'' infections that do not respond to vancomycin or metronidazole are sometimes treated with oral [[rifaximin]]. [[Fidaxomicin]], a new alternative, has been approved for treatment as of mid-2011.  A small number of academic institutions have successfully treated pseudomembranous colitis with fecal transplants, but this therapy is typically reserved for severe recurrent infections and has demonstrated favorable outcomes for cases that are not curable by antimicrobial options.<ref>Brandt LJ, Reddy SS. Fecal microbiota transplantation for recurrent Clostridium difficile infection. J Clin Gastroenterol. 2011;45(suppl):S159–S167. </ref>


''[[Saccharomyces boulardii]]'' (a yeast) has been shown in one small study of 124 patient to reduce the recurrence rate of pseudomembranous colitis.<ref>{{cite journal | author=McFarland LV, Surawicz CM, Greenberg RN, ''et al.'' | title=A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease | journal=JAMA | year=1994 | volume=271 | issue=24 | pages=1913&ndash;18 | id=PMID 8201735 }}</ref>  A number of mechanisms have been proposed to explain this effect.
[[Cholestyramine]] and other [[bile acid sequestrants]] should not be used as adjunctive therapy because, though they may bind the ''C. difficile'' toxin, they can also inhibit the effects of the primary antibiotic.


[[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.  
Several probiotic therapies have been used as adjunct therapies for pseudomembranous colitis. ''[[Saccharomyces boulardii]]'' (similar to baker's yeast) has been shown in one small study of 124 patients to reduce the recurrence rate of pseudomembranous colitis.<ref>{{cite journal | author=McFarland LV, Surawicz CM, Greenberg RN, ''et al.'' | title=A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease | journal=[[Journal of the American Medical Association|JAMA]] | year=1994 | volume=271 | issue=24 | pages=1913&ndash;18 | pmid=8201735  | doi=10.1001/jama.271.24.1913}}</ref>  A number of mechanisms have been proposed to explain this effect. [[Fecal bacteriotherapy]], a medical treatment which involves restoration of colon homeostasis by reintroducing normal bacterial flora using faecal material obtained from a healthy donor, has been successfully used to treat acute pseudomembranous colitis.<ref>{{cite journal | author = Schwan A, Sjölin S, Trottestam U, Aronsson B | title = Relapsing clostridium difficile enterocolitis cured by rectal infusion of homologous faeces. | journal = Lancet | volume = 2 | issue = 8354 | pages = 845 | year = 1983 | pmid = 6137662 | doi = 10.1016/S0140-6736(83)90753-5}}</ref><ref>{{cite journal | author = Paterson D, Iredell J, Whitby M | title = Putting back the bugs: bacterial treatment relieves chronic diarrhoea. | journal = Med J Aust | volume = 160 | issue = 4 | pages = 232–3 | year = 1994 | pmid = 8309401}}</ref><ref>{{cite journal | author = Borody T | title = "Flora Power"-- fecal bacteria cure chronic C. difficile diarrhea. | journal = Am J Gastroenterol | volume = 95 | issue = 11 | pages = 3028–9 | year = 2000 | pmid = 11095314 | doi = 10.1111/j.1572-0241.2000.03277.x}} [http://www.cdd.com.au/pdf/paper32.pdf PDF]</ref>


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 in life-threatening cases.


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


==Prevention==
{{MedCondContrAbs
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 <ref name="pmid17604300">{{cite journal |author=Hickson M, D'Souza AL, Muthu N, ''et al'' |title=Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial |journal=BMJ |volume=335 |issue=7610 |pages=80 |year=2007 |pmid=17604300 |doi=10.1136/bmj.39231.599815.55}}</ref>. Although intriguing, several other studies have been unable to demonstrate any benefit of oral supplements of similar bacteria at preventing CDAD.


==Related Chapters==
|MedCond = Pseudomembranous enterocolitis|Loperamide}}
*[[Clostridium difficile]]
* [[Diphenoxylate hydrochloride and atropine sulfate]]


==References==
==References==
{{Reflist|2}}


==External links==
{{reflist|2}}
*[http://www.thebody.com/pwa/sacc.html PWA Health Group - Saccharomyces boulardii Info Sheet]
 
{{Bacterial diseases}}
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[[de:Antibiotikaassoziierte Kolitis]]
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[[hr:Pseudomembranozni kolitis]]
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[[no:Pseudomembranøs kolitt]]


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Latest revision as of 18:50, 18 September 2017

Pseudomembranous colitis
Classification and external resources
Micrograph of a colonic pseudomembrane in Clostridium difficile colitis, a type of pseudomembranous colitis.
ICD-10 A04.7
ICD-9 008.45
DiseasesDB 2820
MedlinePlus 000259
eMedicine med/1942 
MeSH D004761

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Main article: Clostridium difficile infection

For patient information, click here.

Synonyms and keywords: antibiotic-associated enterocolitis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Pseudomembranous enterocolitis is an acute inflammation of the intestinal mucosa that is characterized by the presence of pseudomembranes or plaques in the small intestine (pseudomembranous enteritis) and the large intestine (pseudomembranous colitis). It is commonly associated with antibiotic therapy. Pathogens that have been implicated to cause pseudomembranous enterocolitis include Clostridium difficile, Clostridium perfringens, Staphylococcus aureus, Klebsiella oxytoca, Salmonella species, and Candida species.

The illness is features by offensive-smelling diarrhea, fever, and abdominal pain. In severe cases, life-threatening complications can develop, such as toxic megacolon.

Pathophysiology

The use of systemic antibiotics, including (but not limited to) any penicillin-based antibiotic such as amoxicillin, cephalosporins, and clindamycin, 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. The net effect is to permit more extensive growth than normal of certain bacteria. Clostridium difficile is one such type of bacterium. In addition to proliferating in the bowel, C. difficile also produces toxins. Without either toxin A or toxin B, C. difficile may colonize the gut, but is unlikely to cause pseudomembranous colitis.[1]

Causes

Causes by Organ System

Cardiovascular No underlying causes
Chemical/Poisoning No underlying causes
Dental No underlying causes
Dermatologic No underlying causes
Drug Side Effect Amoxicillin, Aztreonam, Cefadroxil, Cefditoren, Ceftazidime, Cefoxitin sodium, Cytarabine, Cefaclor, Doxorubicin Hydrochloride, Imipenem-Cilastatin, Lincomycin Hydrochloride, Lomefloxacin hydrochloride, Oxacillin, Trovafloxacin mesylate
Ear Nose Throat No underlying causes
Endocrine No underlying causes
Environmental No underlying causes
Gastroenterologic No underlying causes
Genetic No underlying causes
Hematologic No underlying causes
Iatrogenic No underlying causes
Infectious Disease No underlying causes
Musculoskeletal/Orthopedic No underlying causes
Neurologic No underlying causes
Nutritional/Metabolic No underlying causes
Obstetric/Gynecologic No underlying causes
Oncologic No underlying causes
Ophthalmologic No underlying causes
Overdose/Toxicity No underlying causes
Psychiatric No underlying causes
Pulmonary No underlying causes
Renal/Electrolyte No underlying causes
Rheumatology/Immunology/Allergy No underlying causes
Sexual No underlying causes
Trauma No underlying causes
Urologic No underlying causes
Miscellaneous No underlying causes

Causes in Alphabetical Order

Epidemiology

In most cases, a patient presenting with pseudomembranous colitis has recently been on antibiotics. Antibiotics disturb the normal bowel bacterial flora. Certain antibiotics, such as ampicillin,[2] have a higher propensity to create an environment where the bacteria causing pseudomembranous colitis can outcompete the normal gut flora. Clindamycin is the antibiotic classically associated with this disorder, but any antibiotic can cause the condition. Though they are not particularly likely to cause pseudomembranous colitis, cephalosporin antibiotics (such as cefazolin and cephalexin) account for a large percentage of cases due to their very frequent use. 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. Some evidence shows proton pump inhibitors are a risk factor for C. difficile infection and pseudomembranous colitis,[3][4] 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).[5] Indeed, one large case-control study showed PPIs are not a risk factor.[6]

Signs and Symptoms

As noted above, pseudomembranous colitis is characterized by diarrhea, abdominal pain, and fever. Usually, the diarrhea is not bloody, although blood may be present if the affected individual is taking blood thinners or has an underlying lower bowel condition, such as inflamed 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 in general 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.


Diagnosis

Pseudomembranous colitis in computertomography
Endoscopic image of pseudomembranous colitis, with yellow pseudomembranes seen on the wall of the sigmoid colon
Pathological specimen showing pseudomembranous colitis

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 six months after antibiotic use. Although some relationship between dose/duration of antibiotic and the likelihood of developing pseudomembranous colitis occurs, it may occur even after a single dose of antibiotic. In fact, the use of a single-dose prophylactic antibiotic is a common practice in surgical and dental patients to prevent infections associated with a procedure. Hence, 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. Use of proton pump inhibitor drugs, such as omeprazole for gastric reflux, or some forms of asthma inhaler, or all drugs with anticholinergic effects that slow the digestive transit time lead to retention of toxins and exacerbate the effects of broad-spectrum antibiotics.

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

Although colonoscopy and sigmoidoscopy are still employed, stool testing for the presence of C. difficile toxins is now often the first-line diagnostic approach. Usually, only two toxins are tested for - toxin A and toxin B - but the organism produces several others. This test is not 100% accurate, with a considerable false-negative rate even with repeat testing.

Another, more recent two-step approach involves testing for the presence of C. difficile in the stool and then testing for toxin production. The first step is performed by testing for the presence of the C. difficile GDH antigen. If the first step is positive, a second test, a PCR assay targeting the toxin genes, is performed.

Prevention

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, however, sponsored by the company that produces the drink.[7] Although intriguing, several other studies have been unable to demonstrate any benefit of oral supplements of similar bacteria at preventing C. difficile-associated diarrhea.

Treatment

The disease is usually treated with either metronidazole or oral vancomycin. Oral metronidazole at doses of 500 mg three times a day for 10 to 14 days can be used for mild to moderate cases of C. difficile. Choice of drug depends on severity of disease and the ability to tolerate and absorb oral medications. Vancomycin treatment does present the risk of the development of vancomycin-resistant Enterococcus, though it is only minimally absorbed into the bloodstream from the gastrointestinal tract. Metronidazole itself has on occasion 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. C. difficile infections that do not respond to vancomycin or metronidazole are sometimes treated with oral rifaximin. Fidaxomicin, a new alternative, has been approved for treatment as of mid-2011. A small number of academic institutions have successfully treated pseudomembranous colitis with fecal transplants, but this therapy is typically reserved for severe recurrent infections and has demonstrated favorable outcomes for cases that are not curable by antimicrobial options.[8]

Cholestyramine and other bile acid sequestrants should not be used as adjunctive therapy because, though they may bind the C. difficile toxin, they can also inhibit the effects of the primary antibiotic.

Several probiotic therapies have been used as adjunct therapies for pseudomembranous colitis. Saccharomyces boulardii (similar to baker's yeast) has been shown in one small study of 124 patients to reduce the recurrence rate of pseudomembranous colitis.[9] A number of mechanisms have been proposed to explain this effect. Fecal bacteriotherapy, a medical treatment which involves restoration of colon homeostasis by reintroducing normal bacterial flora using faecal material obtained from a healthy donor, has been successfully used to treat acute pseudomembranous colitis.[10][11][12]

If antibiotics do not control the infection, the patient may require a colectomy (removal of the colon) for treatment of the colitis in life-threatening cases.

Contraindicated medications

Pseudomembranous enterocolitis is considered an absolute contraindication to the use of the following medications:

References

  1. ↑ Sarah A. Kuehne, Stephen T. Cartman, John T. Heap, Michelle L. Kelly, Alan Cockayne & Nigel P. Minton (2010). "The role of toxin A and toxin B inClostridium difficile infection". Nature. 467 (7316): 711–3. doi:10.1038/nature09397. PMID 20844489.
  2. ↑ Katzung, Bertram G. (2007). Basic and Clinical Pharmacology. New York, NY: McGraw Hill Medical. p. 733. ISBN 978-0-07-145153-6.
  3. ↑ Deshpande A; Pant C; Pasupuleti V; Rolston, David D.K.; Jain, Anil; Deshpande, Narayan; Thota, Priyaleela; Sferra, Thomas J.; Hernandez, Adrian V. (2011). "Association between Proton Pump Inhibitor therapy and Clostridium difficile infection in a Meta-Analysis". Clin. Gastroenterol. Hepatol. 10 (3): 225–33. doi:10.1016/j.cgh.2011.09.030. PMID 22019794. Unknown parameter |author-separator= ignored (help); Invalid |display-authors=3. (help)
  4. ↑ 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&ndash, 48. doi:10.1503/cmaj.060284. PMC 1569908. PMID 17001054.
  5. ↑ 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 (9): 1254&ndash, 60. doi:10.1086/496986. PMID 16206099.
  6. ↑ 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&ndash, 6. doi:10.1086/508453. PMID 17051491.
  7. ↑ 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. PMC 1914504. PMID 17604300.
  8. ↑ Brandt LJ, Reddy SS. Fecal microbiota transplantation for recurrent Clostridium difficile infection. J Clin Gastroenterol. 2011;45(suppl):S159–S167.
  9. ↑ 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&ndash, 18. doi:10.1001/jama.271.24.1913. PMID 8201735.
  10. ↑ Schwan A, Sjölin S, Trottestam U, Aronsson B (1983). "Relapsing clostridium difficile enterocolitis cured by rectal infusion of homologous faeces". Lancet. 2 (8354): 845. doi:10.1016/S0140-6736(83)90753-5. PMID 6137662.
  11. ↑ 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.
  12. ↑ Borody T (2000). ""Flora Power"-- fecal bacteria cure chronic C. difficile diarrhea". Am J Gastroenterol. 95 (11): 3028–9. doi:10.1111/j.1572-0241.2000.03277.x. PMID 11095314. PDF
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