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| style="text-align: center; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); font-size: 120%;" | [[Clostridium difficile infection|{{fontcolor|#F8F8FF|''Clostridium difficile'' infection}}]]
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[[{{PAGENAME}}#Overview|{{fontcolor|#F8F8FF|Overview}}]]
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[[{{PAGENAME}}#Diagnostic Criteria|{{fontcolor|#F8F8FF|Diagnostic Criteria}}]]
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[[{{PAGENAME}}#Classification|{{fontcolor|#F8F8FF|Classification}}]]
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[[{{PAGENAME}}#Risk Factors|{{fontcolor|#F8F8FF|Risk Factors}}]]
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[[{{PAGENAME}}#Complete Diagnostic Approach|{{fontcolor|#F8F8FF|Complete Diagnostic Approach}}]]
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[[{{PAGENAME}}#Management|{{fontcolor|#F8F8FF|Management}}]]
<li>[[{{PAGENAME}}#Mild Disease|{{fontcolor|#F8F8FF|Mild Disease}}]]</li>
<li>[[{{PAGENAME}}#Moderate Disease|{{fontcolor|#F8F8FF|Moderate Disease}}]]</li>
<li>[[{{PAGENAME}}#Severe Disease|{{fontcolor|#F8F8FF|Severe Disease}}]]</li>
<li>[[{{PAGENAME}}#Complicated Disease|{{fontcolor|#F8F8FF|Complicated Disease}}]]</li>
<li>[[{{PAGENAME}}#First Recurrence|{{fontcolor|#F8F8FF|First Recurrence}}]]</li>
<li>[[{{PAGENAME}}#Second or Further Recurrence|{{fontcolor|#F8F8FF|Second or Further Recurrence}}]]</li>
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{{fontcolor|#F8F8FF|Dos and Don'ts}}
<li>[[{{PAGENAME}}#Dos|{{fontcolor|#F8F8FF|Dos}}]]</li>
<li>[[{{PAGENAME}}#Don'ts|{{fontcolor|#F8F8FF|Don'ts}}]]</li>
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__NOTOC__
__NOTOC__
{{CMG}}; {{AE}} {{M.P}}, {{Rim}}
{{CMG}}
 
==Overview==
 
 
 
 
 
==Diagnostic Criteria==
 
 


{{SK}} CDI


==Overview==
''[[Clostridium difficile]]'' infection (CDI) is defined as the acute onset of [[diarrhea]] (≥ 3 unformed stools in ≤24 hours) with either documented toxigenic Clostridium difficile (C. difficile) or its toxin, or colonoscopic or histopathological findings of [[pseudomembranous colitis]] in the absence of any other documented cause of diarrhea.<ref name="pmid20307191">{{cite journal| author=Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC et al.| title=Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). | journal=Infect Control Hosp Epidemiol | year= 2010 | volume= 31 | issue= 5 | pages= 431-55 | pmid=20307191 | doi=10.1086/651706 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20307191  }} </ref>


==Classification==
==Classification==
* '''Health-care facility onset health-care facility associated (HO-HCFA)''': Onset of symptoms within 3 days of admission to a health-care facility.
* '''Community onset health-care facility associated (CO-HCFA)''': Onset of symptoms within 4 weeks of discharge from a health-care facility.
* '''Community onset (CA)''': Onset of symptoms outside health-care facility or <3 days after admission to a health-care facility and has not been discharged from health-care facility in the previous 12 weeks.
* '''Indeterminate or unknown''': Onset of symptoms after being discharged from a health-care facility 4-12 weeks previously.<ref name="pmid23439232">{{cite journal| author=Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH et al.| title=Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 4 | pages= 478-98; quiz 499 | pmid=23439232 | doi=10.1038/ajg.2013.4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23439232  }} </ref>


==Causes==
===Life Threatening Causes===
Clostridium difficile infection can be a life-threatening condition and must be treated as such irrespective of the underlying cause.


===Common Causes===
* [[Cephalosporins]]<ref name="pmid17116920">{{cite journal| author=Bartlett JG| title=Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. | journal=Ann Intern Med | year= 2006 | volume= 145 | issue= 10 | pages= 758-64 | pmid=17116920 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17116920  }} </ref>
* [[Clindamycin]]<ref name="pmid10572152">{{cite journal| author=Johnson S, Samore MH, Farrow KA, Killgore GE, Tenover FC, Lyras D et al.| title=Epidemics of diarrhea caused by a clindamycin-resistant strain of Clostridium difficile in four hospitals. | journal=N Engl J Med | year= 1999 | volume= 341 | issue= 22 | pages= 1645-51 | pmid=10572152 | doi=10.1056/NEJM199911253412203 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10572152  }} </ref>
*[[Doxycycline]]
* [[Fluoroquinolones]]<ref name="pmid16206099">{{cite journal| author=Pépin J, Saheb N, Coulombe MA, Alary ME, Corriveau MP, Authier S 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 | issue= 9 | pages= 1254-60 | pmid=16206099 | doi=10.1086/496986 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16206099  }} </ref>
* [[H2 antagonist|Histamine 2 receptor antagonists]]<ref name="pmid22525304">{{cite journal| author=Kwok CS, Arthur AK, Anibueze CI, Singh S, Cavallazzi R, Loke YK| title=Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 7 | pages= 1011-9 | pmid=22525304 | doi=10.1038/ajg.2012.108 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22525304  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22910967 Review in: Ann Intern Med. 2012 Aug 21;157(4):JC2-13]  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23220471 Review in: Evid Based Med. 2013 Oct;18(5):193-4] </ref>
* [[Penicillins]]
* [[Proton pump inhibitor|Proton-pump inhibitors (PPIs)]]<ref name="pmid22710578">{{cite journal| author=Janarthanan S, Ditah I, Adler DG, Ehrinpreis MN| title=Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 7 | pages= 1001-10 | pmid=22710578 | doi=10.1038/ajg.2012.179 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22710578  }} </ref>
* [[Rifapentin]]


==Management==
{{Family tree/start}}
{{familytree | | | | | A01 | | | | | A01=<div style="float: left; text-align: left; height: 14em; width: 20em; padding:1em;"> '''Characterize the symptoms:'''<br>
❑ [[Diarrhea]] (onset, duration, pattern, bloody, mucous or watery) <br> ❑ Mental status change <br> ❑ [[Fever]] <br> ❑ [[Abdominal pain]] <br> ❑ [[Abdominal distention]] <br> ❑ [[Nausea]] <br> ❑ [[Vomiting]] <br> ❑ [[Loss of appetite]]</div>}}
{{familytree | | | | | |!| | | | | |}}
{{familytree | | | | | B01 | | | | | B01=<div style="float: left; text-align: left; height: 19em; width: 20em; padding:1em;">'''Assess volume status:'''
----
❑ General condition <br>
❑ Thirst <br>
❑ [[Pulse]] <br>
❑ [[Blood pressure]] <br>
❑ Eyes <br>
❑ Mucosa
----
'''Examine the patient:'''<br>
❑ Extremities ([[edema]]) <br> ❑ Abdomen distension or tenderness <br> ❑ Anorectal bleeding </div>}}
{{familytree | | | | | |!| | | | }}
{{familytree | | | | | C01 | | | C01= <div style="float: left; text-align: left; height: 16em; width: 20em; padding:1em;">'''Order tests:'''<br>
❑ [[CBC]]  <br>
❑ [[ESR]]<br>
❑ [[Serum electrolytes]]  <br>
❑ Total serum [[protein]] and [[albumin]]<br>
❑ [[Diarrhea laboratory findings|Stool analysis]]<br>
❑ [[Urinalysis]] <br>
❑ [[BUN]] <br>
❑ [[Creatinine]]<br>
❑ [[Serum glucose]] </div>}}
{{familytree | | | | | |!| | | | }}
{{familytree | | | | | D01 | | | D01= '''Test the liquid stool for C. difficile:'''<br><div style="float: left; text-align: left; height: 9em; width: 20em; padding:1em;">
❑ Nucleic acid amplification tests (NAAT) for [[C. difficile]] toxin genes such as [[PCR]], '''OR''' <br>
❑ Two or three steps glutamate dehydrogenase (GDH) screening with subsequent toxin A and B enzyme immunoassay
</div>}}
{{familytree | | | | | |!| | | | }}
{{familytree | | | | | E01 | | | E01= <div style="float: left; text-align: left; height: 16em; width: 20em; padding:1em;">❑ '''Discontinue any inciting antibiotics''' <br>❑ '''Stop anti-motility drugs''' <br>❑ '''Take infection control precautions:''' <br>♦ Place the patient in a private room or in a room with another patient when CDI is suspected or confirmed<br> ♦ Use hand hygiene and barrier precautions<br> ♦ Use single use disposable equipment <br>♦ Disinfect environmental surfaces <br>❑ '''Assess the severity of the patient's condition to tailor the management'''</div>}}
{{familytree | | | | | |!| | | | | }}
{{familytree | |,|-|-|-|+|-|-|-|.| |}}
{{familytree | F01 | | F02 | | F03 | F01='''Mild or moderate initial episode''' <br> <div style="float: left; text-align: left; height: 14em; width: 20em; padding:1em;">❑ [[Diarrhea]]<br> ❑ Absence of peritoneal signs and symptoms</div>| F02= '''Severe initial episode''' <br><div style="float: left; text-align: left; height: 14em; width: 20em; padding:1em;">❑ [[Serum albumin]] <3g/dl <br>'''Plus''' any '''ONE''' of the following:<br>
❑ WBC ≥15,000 cells/mm3 <br>
❑ Abdominal tenderness </div>| F03= '''Complicated severe initial episode''' <br><div style="float: left; text-align: left; height: 17em; width: 20em; padding:1em;">❑ Admission to the intensive care unit for CDI <br> ❑ [[Hypotension]] with or without required use of vasopressors <br> ❑ [[Fever]] ≥38.5 °C  <br> ❑ [[Ileus]] or significant abdominal distention <br> ❑ Mental status changes  <br> ❑ Serum [[lactate]] levels >2.2 mmol/l  <br> ❑ [[WBC]] ≥35,000 cells/mm3 or <2,000 cells/mm3  <br> ❑ End organ failure ([[mechanical ventilation]], [[renal failure]], etc.) </div> }}
{{familytree | |!| | | |!| | | |!| | }}
{{familytree | |!| | | |!| | | G03 | G03= <div style="float: left; text-align: left; height: 9em; width: 20em; padding:1em;">❑ Deliver supportive care<br> ♦ IV fluid resuscitation <br>♦ Electrolyte replacement <br>♦ VTE prophylaxis <br>❑ Order a [[CT scan]] <br> ❑ Obtain a surgical consult </div>}}
{{familytree | |!| | | |!| | |,|^|-|-|-|.| | }}
{{familytree | H01 | | H02 | | H03 | | H04 | H01=  <div style="float: left; text-align: left; height: 9em; width: 20em; padding:1em;">❑ '''Administer antibiotics:''' <br>♦ [[Metronidazole]] 500 mg 3 times/day, orally, for 10 days, OR <br>♦ [[Vancomycin]] 125 mg 4 times/day in the case of allergy to metronidazole, pregnancy or breastfeeding </div>| H02=  <div style="float: left; text-align: left; height: 9em; width: 20em; padding:1em;">❑ '''Administer antibiotics:''' <br> [[Vancomycin]] 125 mg 4 times/day for 10 days </div>| H03= '''Absence of abdominal distention:''' <br> <div style="float: left; text-align: left; height: 9em; width: 20em; padding:1em;">❑ '''Administer antibiotics:''' <br>♦ [[Vancomycin]] 125 mg 4 times/day, orally or by NG tube, '''PLUS''' <br> ♦ [[Metronidazole]] 500 mg 3 times/day
----
❑ Continue oral or enteral feeding </div>
| H04= '''Presence of significant abdominal distention:''' <br><div style="float: left; text-align: left; height: 9em; width: 20em; padding:1em;"> ❑ '''Administer antibiotics:''' <br>♦ [[Vancomycin]] 500 mg 4 times/day, orally or by NG tube, '''PLUS''' <br>♦ [[Vancomycin]] 500 mg in a volume of 500 mL, per rectum, 4 times/day, '''PLUS''' <br>♦ IV [[Metronidazole]] 500 mg 3 times/day </div>}}
{{familytree | |!| | | |!| | | |!| | |!| |}}
{{familytree | H05 | | |!| | | |!| | |!| | H05= <div style="float: left; text-align: left; height: 5em; width: 20em; padding:1em;">'''In case of failure to respond within 5-7 days:'''<br>❑ Switch to [[Vancomycin]] 125 mg 4 times/day</div>}}
{{familytree | |`|-|-|-|+|-|-|-|^|-|-|'| | }}
{{familytree | | | | | I01 | | | | | I01= '''First recurrence?''' <br> <div style="float: left; text-align: left; height: 4em; width: 20em; padding:1em;"> ❑ Repeat the treatment of the initial episode <br> ❑  Use [[vancomycin]] if severe</div>}}
{{familytree | | | | | |!| | | | | | }}
{{familytree | | | | | J01 | | | | | J01= '''Second recurrence?''' <br> <div style="float: left; text-align: left; height: 3em; width: 20em; padding:1em;">❑ Administer [[vancomycin]] in a tapered and/or pulsed way </div>}}
{{familytree | | | | | |!| | | | | | }}
{{familytree | | | | | K01 | | | | | K01= '''Third recurrence?''' <br> <div style="float: left; text-align: left; height: 3em; width: 20em; padding:1em;">❑ Consider fecal microbiota transplant (FMT) </div>}}
{{Family tree/end}}
<br>
The algorithm is based on the 2013 American Journal of Gastroenterology guidelines.<ref name="pmid23439232">{{cite journal| author=Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH et al.| title=Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 4 | pages= 478-98; quiz 499 | pmid=23439232 | doi=10.1038/ajg.2013.4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23439232  }} </ref>


==Do's==
* Only unformed stools from patients with diarrhea should be tested for C. difficile.  Inform the laboratory when a patient with [[ileus]] and complicated disease has a formed stool.


* Rectal swabs can be used for PCR and thus may be useful in timely diagnosis of patients with ileus.<ref name="pmid20307191">{{cite journal| author=Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC et al.| title=Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). | journal=Infect Control Hosp Epidemiol | year= 2010 | volume= 31 | issue= 5 | pages= 431-55 | pmid=20307191 | doi=10.1086/651706 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20307191  }} </ref><ref name="pmid22911648">{{cite journal| author=Kundrapu S, Sunkesula VC, Jury LA, Sethi AK, Donskey CJ| title=Utility of perirectal swab specimens for diagnosis of Clostridium difficile infection. | journal=Clin Infect Dis | year= 2012 | volume= 55 | issue= 11 | pages= 1527-30 | pmid=22911648 | doi=10.1093/cid/cis707 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22911648  }} </ref>
==Risk Factors==
 
 
 
 
 
 
==Complete Diagnostic Approach==
 
 
 
 
 
 
 
 
==Dos and Don'ts==
 
===Do's===
 
 
 
 
 


* Begin empiric therapy for C. difficile regardless of the laboratory results among patients with high suspicion for CDI.
===Don'ts===


* Add [[vancomycin]] therapy delivered via enema to treatments in patients in whom oral antibiotics cannot reach a segment of the colon, such as with Hartman’s pouch, [[ileostomy]], or colon diversion.


* Test for C. difficile among patients with diarrhea in the context of immunosuppression, such as [[malignancy]], [[chemotherapy]], [[corticosteroid]] therapy, organ transplantation, and [[cirrhosis]].


* Test for C. difficile among pregnant or periparturient women with diarrhea because of the increased rate of maternal and fetal mortality.<ref name="pmid16319813">{{cite journal| author=Centers for Disease Control and Prevention (CDC)| title=Severe Clostridium difficile-associated disease in populations previously at low risk--four states, 2005. | journal=MMWR Morb Mortal Wkly Rep | year= 2005 | volume= 54 | issue= 47 | pages= 1201-5 | pmid=16319813 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16319813  }} </ref>


===Management of CDI in IBD Patients===
* Test for C. difficile among all patients with [[IBD]] who develop diarrhea following recent hospitalization or antibiotic use or in the setting of previously quiescent disease or with a disease flare.
* Test for C. difficile among all patients with an IBD flare.
* Consider the simultaneous treatment for [[IBD]] flare and empiric therapy against CDI among IBD patients who have severe colitis.<ref name="pmid23439232">{{cite journal| author=Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH et al.| title=Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 4 | pages= 478-98; quiz 499 | pmid=23439232 | doi=10.1038/ajg.2013.4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23439232  }} </ref>


==Don't s==
* Don't screen for C. difficle among patients without diarrhea.
* Don't repeat testing for negative tests.
* Don't use anti-peristaltic agents to control diarrhea for confirmed or suspected CDI patients, as they may obscure symptoms and precipitate complicated disease.<ref name="pmid19191646">{{cite journal| author=Koo HL, Koo DC, Musher DM, DuPont HL| title=Antimotility agents for the treatment of Clostridium difficile diarrhea and colitis. | journal=Clin Infect Dis | year= 2009 | volume= 48 | issue= 5 | pages= 598-605 | pmid=19191646 | doi=10.1086/596711 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19191646  }} </ref>
* Repeat testing should be discouraged as it increases the likelihood of false positives and if requested, the physician should confer with the laboratory to explain the clinical rationale.<ref name="pmid20923255">{{cite journal| author=Deshpande A, Pasupuleti V, Pant C, Hall G, Jain A| title=Potential value of repeat stool testing for Clostridium difficile stool toxin using enzyme immunoassay? | journal=Curr Med Res Opin | year= 2010 | volume= 26 | issue= 11 | pages= 2635-41 | pmid=20923255 | doi=10.1185/03007995.2010.522155 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20923255  }} </ref><ref name="pmid20686078">{{cite journal| author=Luo RF, Banaei N| title=Is repeat PCR needed for diagnosis of Clostridium difficile infection? | journal=J Clin Microbiol | year= 2010 | volume= 48 | issue= 10 | pages= 3738-41 | pmid=20686078 | doi=10.1128/JCM.00722-10 | pmc=PMC2953130 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20686078  }} </ref>
* Empiric therapy for CDI should not be discontinued or withheld in patients with a high pre-test suspicion for CDI.
* Dont treat asymptomatic C.Difficle carriers as treating such patients may increase the shedding of spores and growth of new resistant strains.<ref name="pmid1322075">{{cite journal| author=Johnson S, Homann SR, Bettin KM, Quick JN, Clabots CR, Peterson LR et al.| title=Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. A randomized, placebo-controlled trial. | journal=Ann Intern Med | year= 1992 | volume= 117 | issue= 4 | pages= 297-302 | pmid=1322075 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1322075  }} </ref>
* Don't test for cure following an episode of clostridium difficile diarrhea.
* The evidence for the use of probiotics, [[Lactobacillus casei]], [[Lactobacillus bulgaricus]], and [[Streptococcus thermophilus]] to decrease the incidence of antibiotic-associated diarrhea is insufficient.<ref name="pmid17604300">{{cite journal| author=Hickson M, D'Souza AL, Muthu N, Rogers TR, Want S, Rajkumar C et al.| title=Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. | journal=BMJ | year= 2007 | volume= 335 | issue= 7610 | pages= 80 | pmid=17604300 | doi=10.1136/bmj.39231.599815.55 | pmc=PMC1914504 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17604300  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18375699 Review in: Evid Based Med. 2008 Apr;13(2):46]  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18364427 Review in: Evid Based Nurs. 2008 Apr;11(2):57] </ref><ref name="pmid23439232">{{cite journal| author=Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH et al.| title=Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 4 | pages= 478-98; quiz 499 | pmid=23439232 | doi=10.1038/ajg.2013.4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23439232  }} </ref>


==References==
==References==

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