Clostridium difficile infection resident survival guide: Difference between revisions

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__NOTOC__
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{{CMG}}; {{AE}} {{M.P}}, {{Rim}}
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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 of Disease Severity|{{fontcolor|#F8F8FF|Classification of Disease Severity}}]]
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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}}]]
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[[{{PAGENAME}}#Dos and Don'ts|{{fontcolor|#F8F8FF|Dos and Don'ts}}]]
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[[{{PAGENAME}}#Guidelines and Resources|{{fontcolor|#F8F8FF|Guidelines and Resources}}]]
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__NOTOC____NOEDITSECTION__
{{Main|Clostridium difficile infection}}
{{CMG}}; Gerald Chi, M.D.


{{SK}} CDI
==Overview==
''Clostridium difficile'' infection is the leading cause to nosocomial diarrhea.  Clinical presentation ranges across a broad spectrum from asymptomatic carriage, to [[diarrhea]]l illness, to complicated disease hallmarked by [[pseudomembranous colitis]], [[toxic megacolon]], or [[bowel perforation]].  Diagnosis is established by the presence of [[diarrhea]]l symptoms coupled with positive stool tests or endoscopic findings.  Therapeutic approach and antibiotic choice should be stratified according to severity of disease and risk of recurrence.


==Definition==  
==Diagnostic Criteria==
[[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>
* '''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==
===Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)===
===Life Threatening Causes===
The diagnosis of ''[[C. difficile]]'' infection should be based on a combination of clinical and laboratory findings. A case definition for the usual presentation includes the following findings:<ref>{{Cite journal| doi = 10.1086/651706| issn = 1559-6834| volume = 31| issue = 5| pages = 431–455| last1 = Cohen| first1 = Stuart H.| last2 = Gerding| first2 = Dale N.| last3 = Johnson| first3 = Stuart| last4 = Kelly| first4 = Ciaran P.| last5 = Loo| first5 = Vivian G.| last6 = McDonald| first6 = L. Clifford| last7 = Pepin| first7 = Jacques| last8 = Wilcox| first8 = Mark H.| last9 = Society for Healthcare Epidemiology of America| last10 = Infectious Diseases Society of America| 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 = Infection Control and Hospital Epidemiology| date = 2010-05| pmid = 20307191}}</ref>
Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. Clostridium difficile infection itself may present or complicate as a life-threatening condition and must be treated as such irrespective of the causes.
* The presence of [[diarrhea]], defined as passage of 3 or more unformed stools in 24 or fewer consecutive hours {{and}}
* A stool test result positive for the presence of toxigenic [[C. difficile]] or its [[toxin]]s {{or}} colonoscopic or histopathologic findings demonstrating [[pseudomembranous colitis]].


===Common Causes===
The same criteria should be used to diagnose recurrent ''[[C. difficile]]'' infection.
* [[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>
===European Society of Clinical Microbiology and Infectious Diseases (ESCMID)===
* [[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>
Diagnosis of ''[[C. difficile]]'' infection is based on the following criteria:<ref>{{Cite journal| doi = 10.1111/1469-0691.12418| issn = 1469-0691| volume = 20 Suppl 2| pages = 1–26| last1 = Debast| first1 = S. B.| last2 = Bauer| first2 = M. P.| last3 = Kuijper| first3 = E. J.| last4 = European Society of Clinical Microbiology and Infectious Diseases| title = European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection| journal = Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases| date = 2014-03| pmid = 24118601}}</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>
* A combination of signs and symptoms, confirmed by microbiological evidence of ''C. difficile'' in stools, in the absence of another cause {{or2}}
* [[Penicillins]]
* Colonoscopic or histopathological findings demonstrating [[pseudomembranous colitis]]
* [[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>
 
Diagnostic tests for ''[[C. difficile]]'' infection include:<ref>{{Cite journal| doi = 10.1111/1469-0691.12418| issn = 1469-0691| volume = 20 Suppl 2| pages = 1–26| last1 = Debast| first1 = S. B.| last2 = Bauer| first2 = M. P.| last3 = Kuijper| first3 = E. J.| last4 = European Society of Clinical Microbiology and Infectious Diseases| title = European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection| journal = Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases| date = 2014-03| pmid = 24118601}}</ref>
* [[Enzyme immunoassay|Enzyme immunoassay (EIA)]]: [[GDH|glutamate dehydrogenase (GDH)]], [[toxins]] A and B
* Nucleic acid amplification tests (NAAT): [[16S ribosomal RNA]], [[GDH]] genes, [[toxin]] genes
* Cell culture cytoxicity assay (CCA)
* Culture of toxigenic ''[[C. difficile]]''
 
==Classification of Disease Severity==
 
===American College of Gastroenterology (ACG)===
Classification of disease severity:<ref>{{Cite journal| doi = 10.1038/ajg.2013.4| issn = 1572-0241| volume = 108| issue = 4| pages = 478–498; quiz 499| last1 = Surawicz| first1 = Christina M.| last2 = Brandt| first2 = Lawrence J.| last3 = Binion| first3 = David G.| last4 = Ananthakrishnan| first4 = Ashwin N.| last5 = Curry| first5 = Scott R.| last6 = Gilligan| first6 = Peter H.| last7 = McFarland| first7 = Lynne V.| last8 = Mellow| first8 = Mark| last9 = Zuckerbraun| first9 = Brian S.| title = Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections| journal = The American Journal of Gastroenterology| date = 2013-04| pmid = 23439232}}</ref>
* '''Mild disease'''
: [[Diarrhea]] as the only symptom
 
* '''Moderate disease'''
: [[Diarrhea]] but without additional symptoms/signs meeting the definition of severe or complicated disease
 
* '''Severe disease'''
: [[Hypoalbuminemia]] (serum [[albumin]] < 3 g/dl) {{and}}
: [[WBC]] ≥ 15,000 cells/mL {{or}} [[abdominal tenderness]] without criteria of complicated disease
 
* '''Complicated disease'''
: Any of the following attributable to ''[[C. difficile]]'' infection:
: Admission to [[intensive care unit]]
: [[Hypotension]] with or without required use of [[vasopressors]]
: [[Fever]] ≥ 38.5°C
: [[Ileus]] (acute [[nausea]], [[emesis]], sudden cessation of [[diarrhea]], significant [[abdominal distention]], or radiological signs consistent with disturbed intestinal transit)
: [[Altered mental status|Mental status changes]]
: [[WBC]] ≥ 35,000 cells/mL or < 2,000 cells/mL
: Serum [[lactate]] levels > 2.2 mmol/l
: Any evidence of end organ failure
 
* '''Recurrent disease'''
: Recurrence within 8 weeks of completion of therapy
 
===Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)===
Initial episode of ''[[C. difficile]]'' infection may be stratified by disease severity as follows:<ref>{{Cite journal| doi = 10.1086/651706| issn = 1559-6834| volume = 31| issue = 5| pages = 431–455| last1 = Cohen| first1 = Stuart H.| last2 = Gerding| first2 = Dale N.| last3 = Johnson| first3 = Stuart| last4 = Kelly| first4 = Ciaran P.| last5 = Loo| first5 = Vivian G.| last6 = McDonald| first6 = L. Clifford| last7 = Pepin| first7 = Jacques| last8 = Wilcox| first8 = Mark H.| last9 = Society for Healthcare Epidemiology of America| last10 = Infectious Diseases Society of America| 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 = Infection Control and Hospital Epidemiology| date = 2010-05| pmid = 20307191}}</ref>
* '''Mild-to-moderate disease'''
: [[Leukocytosis]] with [[WBC]] < 15,000 cells/mL {{and2}} serum [[creatinine]] < 1.5 times the premorbid level
 
* '''Severe disease'''
: [[Leukocytosis]] with [[WBC]] ≥ 15,000 cells/mL {{or}} serum [[creatinine]] ≥ 1.5 times the premorbid level
 
* '''Severe, complicated disease'''
: [[Hypotension]] or [[shock]], [[ileus]], [[megacolon]]
 
===European Society of Clinical Microbiology and Infectious Diseases (ESCMID)===
'''Severe disease''' is defined as an episode of ''[[C. difficile]]'' infection with:<ref>{{Cite journal| doi = 10.1111/1469-0691.12418| issn = 1469-0691| volume = 20 Suppl 2| pages = 1–26| last1 = Debast| first1 = S. B.| last2 = Bauer| first2 = M. P.| last3 = Kuijper| first3 = E. J.| last4 = European Society of Clinical Microbiology and Infectious Diseases| title = European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection| journal = Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases| date = 2014-03| pmid = 24118601}}</ref>
* One or more specific signs and symptoms of severe [[colitis]] {{or2}}
* A complicated course of disease, with significant systemic [[toxin]] effects and [[shock]], resulting in need for [[ICU|intensive care unit]] admission, [[colectomy]], or death.
 
Characteristics that correlate with severity of [[colitis]]:<ref>{{Cite journal| doi = 10.1111/1469-0691.12418| issn = 1469-0691| volume = 20 Suppl 2| pages = 1–26| last1 = Debast| first1 = S. B.| last2 = Bauer| first2 = M. P.| last3 = Kuijper| first3 = E. J.| last4 = European Society of Clinical Microbiology and Infectious Diseases| title = European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection| journal = Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases| date = 2014-03| pmid = 24118601}}</ref>
* Physical examination
: [[Fever]] (core body temperature > 38.5°C)
: [[Rigors]] (uncontrollable shaking and a feeling of cold followed by a rise in body temperature)
: [[Hemodynamic instability]] including signs of [[distributive shock]]
: [[Respiratory failure]] requiring [[mechanical ventilation]]
: Signs and symptoms of [[peritonitis]]
: Signs and symptoms of colonic [[ileus]]
 
* Laboratory investigations
: Marked [[leukocytosis]] ([[leukocyte]] count > 15,000 cells/mL)
: Marked [[bandemia|left shift]] ([[band neutrophil]]s > 20% of leukocytes)
: Rise in serum [[creatinine]] (> 50% above the baseline)
: Elevated serum [[lactate]] (5 mmol/L)
: Markedly reduced serum [[albumin]] (< 3 mg/dl)
* [[Colonoscopy]] or [[sigmoidoscopy]]
: [[Pseudomembranous colitis]]
 
* Imaging
: Distention of [[large intestine]] (> 6 cm in transverse width of colon)
: Colonic wall thickening including low-attenuation mural thickening
: Pericolonic fat stranding
: [[Ascites]] not explained by other causes
 
==Risk Factors==
The most important risk factor remains [[antibiotic|antibiotic use]].  Other established risk factors include:<ref>{{Cite journal| doi = 10.1016/j.mayocp.2012.07.016| issn = 1942-5546| volume = 87| issue = 11| pages = 1106–1117| last1 = Khanna| first1 = Sahil| last2 = Pardi| first2 = Darrell S.| title = Clostridium difficile infection: new insights into management| journal = Mayo Clinic Proceedings| date = 2012-11| pmid = 23127735| pmc = PMC3541870}}</ref>
* [[Elderly|Advanced age]]
* [[Chemotherapy]]
* [[Chronic kidney disease]]
* Consumption of processed meat
* Contact with active carriers
* [[Cystic fibrosis]]
* [[Diabetes mellitus]]
* [[Hypoalbuminemia]]
* [[Immunosuppression]], [[immunodeficiency]], or [[human immunodeficiency virus]]
* Increased risk with prolonged use or multiple [[antibiotics]]
* [[Inflammatory bowel disease]]
* [[Liver cirrhosis]]
* [[Malignancy]]
* [[Malnutrition]]
* Nursing home or long-term care facility residence
* Presence of comorbid conditions
* Presence of [[gastrostomy]] or [[Feeding tube#Jejunal feeding tube|jejunostomy tube]]
* Previous [[gastrointestinal]] [[surgery]] or [[endoscopic]] procedure
* Previous hospitalization and prolonged length of hospital stay
* Solid organ or [[hematopoietic stem cell transplantation]]
* Use of [[proton pump inhibitor]]s
 
Use of the following [[antibiotics]] has been associated with ''[[C. difficile]]'' infection:<ref>{{Cite journal| doi = 10.1056/NEJMra1403772| issn = 1533-4406| volume = 372| issue = 16| pages = 1539–1548| last1 = Leffler| first1 = Daniel A.| last2 = Lamont| first2 = J. Thomas| title = Clostridium difficile infection| journal = The New England Journal of Medicine| date = 2015-04-16| pmid = 25875259}}</ref>
* '''Very common'''
: [[Clindamycin]]
: [[Ampicillin]]
: [[Amoxicillin]]
: [[Cephalosporins]]
: [[Fluoroquinolones]]
 
* '''Somewhat common'''
: [[Penicillins]]
: [[Sulfonamides]]
: [[Trimethoprim]]
: [[Trimethoprim-Sulfamethoxazole]]
: [[Macrolides]]
 
* '''Uncommon'''
: [[Aminoglycosides]]
: [[Bacitracin]]
: [[Metronidazole]]
: [[Teicoplanin]]
: [[Rifampin]]
: [[Chloramphenicol]]
: [[Tetracyclines]]
: [[Carbapenems]]
: [[Daptomycin]]
: [[Tigecycline]]
 
==Complete Diagnostic Approach==
<span style="font-size: 85%;">
'''Abbreviations''':
ALP, alkaline phosphatase;
ALT, alanine aminotransferase;
AST, aspartate aminotransferase;
CBC, complete blood count;
DC, differential count;
EIA, enzyme immunoassay;
GDH, glutamate dehydrogenase;
NAAT, nucleic acid amplification test;
PCR, polymerase chain reaction;
SMA-7, sequential multiple analysis-7.
</span>
 
<div style="font-size: 90%;">
{{Familytree/start}}
{{Familytree|boxstyle=width: 700px; text-align: left; font-size: 100%; padding: 0px;| A01 | | |A01=<div style="padding: 0px 10px;">
==''Clostridium difficile'' Infection==
* [[Diarrhea]] (passage of 3 or more unformed stools in ≤ 24 hours) with microbiological evidence of ''[[C. difficile]]''
* [[Colonoscopic]] or histopathological findings demonstrating pseudomembranous colitis
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{{Familytree|boxstyle=width: 700px; text-align: left; font-size: 100%; padding: 0px;| |!| | | |}}
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==Focused History==
* Characterize the symptoms:
:* [[Abdominal discomfort]]
:* [[Poor appetite]]
:* [[Diarrhea]]
:* [[Nausea]]
:* [[Vomiting]]
:* [[Bloating]]
:* [[Belching]]
:* [[Flatulence]]
:* [[Constipation]] or [[obstipation]]
* Other relevant history:
:* Risk factors ([[{{PAGENAME}}#Risk Factors|details]])
:* Comorbidities
:* Recent sick contacts
:* Recent hospitalizations
:* Prior use of [[antibiotics]]
:* [[Immunosuppressive state]]
:* Travel history
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==Physical Examination==
* Vital signs ([[body temperature]], [[pulse rate]], [[respiration rate]], [[blood pressure]])
* Signs of [[ileus]] ([[abdominal distention|distended and tympanic abdomen]] with [[tenderness]], [[bowel sounds|hypoactive bowel sounds]])
* Signs of [[peritonitis]] ([[rebound tenderness]], [[abdominal guarding]], [[bowel sounds|hypoactive bowel sounds]])
* Signs of [[dehydration]] ([[capillary refill|delayed capillary refill]], [[dehydration|decreased skin turgor]], abnormal respiratory pattern)
* Signs of [[respiratory distress]] ([[tachypnea]], [[tachycardia]], abnormal [[breath sounds]])
* Signs of [[shock|multiple organ failure]] ([[cold and clammy skin]], [[shock|tissue hypoperfusion]])
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==Laboratory Workup and Imaging Study==
* [[Complete blood count|Complete blood count with differential]]
* [[Basic metabolic panel|Basic metabolic panel including urea nitrogen and creatinine]]
* [[AST]], [[ALT]], [[bilirubin]], [[alkaline phosphatase]], [[albumin]], [[lactate]]
* Consider abdominal [[CT scan]] or [[colonoscopy]] in severe disease or concurrent [[inflammatory bowel disease]]
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==Other Investigation==
Positive results of either [[EIA]] or [[NAAT]] should prompt treatment.
* [[GDH]] (high sensitivity, low specificity): screening test
* [[EIA]] for toxins (low sensitivity, high specificity): confirmatory test
* [[NAAT]] (high sensitivity, high specificity): standard diagnostic test
</div>}}
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</div>


==Management==
==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: 22em; width: 20em; padding:1em;">'''Examine the patient:'''
[[Acute diarrhea resident survival guide#Evaluation of Volume Status by Dhaka Method|1. Assess volume status:]]<br>
❑ General condition <br>
❑ Thirst <br>
❑ [[Pulse]] <br>
❑ [[Blood pressure]] <br>
❑ Eyes <br>
❑ Mucosa
----
[[2. General examination:]]<br>
❑ Extremities ([[edema]]) <br> ❑ Abdomen (distension or tenderness) <br> ❑ Anorectal (Bleeding) <br> ❑ CVS <br> ❑ RS </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: 12em; width: 20em; padding:1em;">
❑ Nucleic acid amplification tests (NAAT) for [[C. difficile]] toxin genes such as [[PCR]] (Standard), 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: 14em; width: 20em; padding:1em;">❑ '''Discontinue any inciting antibiotics''' <br>❑ '''Stop anti-motility drugs''' <br>❑ '''Take infection control precaution:''' <br>♦ Place the patient in a private room or in a room with another patient when CDI is suspected or confirmed<br> ♦ Use and hygiene and barrier precautions<br> ♦ Use single use disposable equipement <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''': <br>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: 3em; 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: 3em; 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 algoithm 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==
===Asymptomatic carrier===
* 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.  
* No treatment indicated
 
===Mild disease===
* Predisposing [[antibiotic]] cessation {{and}}
* [[Hydration]] {{and}}
* Monitoring of clinical status {{and}}
* Administration of [[metronidazole]] (500 mg three times per day) {{or2}}
: Close outpatient monitoring without the administration of [[antibiotics]]
 
===Moderate disease===
* Consideration of hospitalization {{and}}
* Cessation of predisposing [[antibiotics]] {{and}}
* [[Hydration]] {{and}}
* Monitoring of clinical status {{and}}
* Administration of [[metronidazole]] (500 mg three times per day) {{or2}}
: Administration of [[vancomycin]] (125 mg orally four times per day for 14 days)
 
===Severe disease===
* Hospitalization {{and}}
* Oral or nasogastric [[vancomycin]] (500 mg four times per day) with or without intravenous [[metronidazole]] (500 mg three times per day) {{or2}}
: Oral [[fidaxomicin]] (200 mg twice a day for 10 days) if the risk of recurrence is high
 
===Complicated disease===
* [[Antibiotics]] as for severe infection {{and}}
* Surgical consultation for subtotal [[colectomy]] or a diverting [[ileostomy]] with [[vancomycin]] colonic lavage {{and}}
* Consideration of [[fecal microbial transplantation]] or additional [[antibiotics]]
 
===First recurrence===
* Oral [[vancomycin]] (125 mg four times per day for 14 days) {{or2}}
: Oral [[fidaxomicin]] (200 mg twice a day for 10 days)
 
===Second or further recurrence===
* [[Vancomycin]] in a tapered and pulsed regimen<sup>†</sup> {{or2}}
* [[Fecal microbial transplantation]] {{or2}}
* [[Fidaxomicin]] (200 mg twice a day for 10 days)<ref>{{Cite journal| doi = 10.1056/NEJMra1403772| issn = 1533-4406| volume = 372| issue = 16| pages = 1539–1548| last1 = Leffler| first1 = Daniel A.| last2 = Lamont| first2 = J. Thomas| title = Clostridium difficile infection| journal = The New England Journal of Medicine| date = 2015-04-16| pmid = 25875259}}</ref> <BR><div style=text-indent: 20px;"><sup>†</sup>125 mg qid x 1 week, 125 mg tid x 1 week, 125 mg bid x 1 week, 125 mg qd x 1 week, 125 mg qod x 1 week, then 125 mg every 3 days x 1 week.</div>
 
==Dos and Don'ts==
 
===Dos===
* Liaise with microbiology service when testing for ''[[Clostridium difficile]]'' from formed stools in a patient with [[ileus]].
* Initiate empiric [[antibiotics]] regardless of the laboratory results when there is a high index of suspicion for ''[[C. difficile]]'' infection.
* [[Vancomycin]] should be delivered via [[enema]] to treat patients in whom oral [[antibiotics]] cannot reach a segment of the colon as in [[Hartmann's operation|Hartmann's pouch]], [[ileostomy]], or [[Bowel resection|colonic diversion]].
* Test for ''[[C. difficile]]'' among patients with diarrhea in the context of [[malignancy]], [[chemotherapy]], [[immunosuppressive therapy]], [[organ transplantation]], [[cirrhosis]], [[inflammatory bowel disease]], or [[pregnancy]].
 
===Don'ts===
* Do NOT test for ''[[C. difficile]]'' in a patient without [[diarrhea]].
* Do NOT repeat test if the results are negative.
* Do NOT perform test of microbiological cure.
* Do NOT treat asymptomatic carriage.
* Do NOT administer [[peristalsis|antiperistaltic agent]]s to patients with suspected or confirmed ''[[C. difficile]]'' infection.
 
==Guidelines and Resources==
 
===Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)===
* Strategies to Prevent ''Clostridium difficile'' Infections in Acute Care Hospitals (2014)<ref>{{Cite journal| issn = 1559-6834| volume = 35 Suppl 2| pages = –48-65| last1 = Dubberke| first1 = Erik R.| last2 = Carling| first2 = Philip| last3 = Carrico| first3 = Ruth| last4 = Donskey| first4 = Curtis J.| last5 = Loo| first5 = Vivian G.| last6 = McDonald| first6 = L. Clifford| last7 = Maragakis| first7 = Lisa L.| last8 = Sandora| first8 = Thomas J.| last9 = Weber| first9 = David J.| last10 = Yokoe| first10 = Deborah S.| last11 = Gerding| first11 = Dale N.| title = Strategies to prevent Clostridium difficile infections in acute care hospitals: 2014 update| journal = Infection Control and Hospital Epidemiology| date = 2014-09| pmid = 25376069}}</ref>
* Clinical Practice Guidelines for ''Clostridium difficile'' Infection in Adults (2010)<ref>{{Cite journal| doi = 10.1086/651706| issn = 1559-6834| volume = 31| issue = 5| pages = 431–455| last1 = Cohen| first1 = Stuart H.| last2 = Gerding| first2 = Dale N.| last3 = Johnson| first3 = Stuart| last4 = Kelly| first4 = Ciaran P.| last5 = Loo| first5 = Vivian G.| last6 = McDonald| first6 = L. Clifford| last7 = Pepin| first7 = Jacques| last8 = Wilcox| first8 = Mark H.| last9 = Society for Healthcare Epidemiology of America| last10 = Infectious Diseases Society of America| 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 = Infection Control and Hospital Epidemiology| date = 2010-05| pmid = 20307191}}</ref>


* 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>
===American College of Gastroenterology (ACG)===
* Guidelines for Diagnosis, Treatment, and Prevention of ''Clostridium difficile'' Infections (2013)<ref>{{Cite journal| doi = 10.1038/ajg.2013.4| issn = 1572-0241| volume = 108| issue = 4| pages = 478–498; quiz 499| last1 = Surawicz| first1 = Christina M.| last2 = Brandt| first2 = Lawrence J.| last3 = Binion| first3 = David G.| last4 = Ananthakrishnan| first4 = Ashwin N.| last5 = Curry| first5 = Scott R.| last6 = Gilligan| first6 = Peter H.| last7 = McFarland| first7 = Lynne V.| last8 = Mellow| first8 = Mark| last9 = Zuckerbraun| first9 = Brian S.| title = Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections| journal = The American Journal of Gastroenterology| date = 2013-04| pmid = 23439232}}</ref>


* 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.
===Association for Professionals in Infection Control and Epidemiology (APIC)===
* Preventing ''Clostridium difficile'' infections (2011)<ref>{{Cite journal| doi = 10.1016/j.ajic.2010.10.011| issn = 1527-3296| volume = 39| issue = 3| pages = 239–242| last1 = Rebmann| first1 = Terri| last2 = Carrico| first2 = Ruth M.| last3 = Association for Professionals in Infection Control and Epidemiology| first3 = null| title = Preventing Clostridium difficile infections: an executive summary of the Association for Professionals in Infection Control and Epidemiology's elimination guide| journal = American Journal of Infection Control| date = 2011-04| pmid = 21371783}}</ref>


* Test for C. difficile among patients with diarrhea in the context of immunosuppression, such as [[malignancy]], [[chemotherapy]], [[corticosteroid]] therapy, organ transplantation, and [[cirrhosis]].
===Eastern Association for the Surgery of Trauma (EAST)===
* Timing and type of surgical treatment of Clostridium difficile-associated disease (2014)<ref>{{Cite journal| doi = 10.1097/TA.0000000000000232| issn = 2163-0763| volume = 76| issue = 6| pages = 1484–1493| last1 = Ferrada| first1 = Paula| last2 = Velopulos| first2 = Catherine G.| last3 = Sultan| first3 = Shahnaz| last4 = Haut| first4 = Elliott R.| last5 = Johnson| first5 = Emily| last6 = Praba-Egge| first6 = Anita| last7 = Enniss| first7 = Toby| last8 = Dorion| first8 = Heath| last9 = Martin| first9 = Niels D.| last10 = Bosarge| first10 = Patrick| last11 = Rushing| first11 = Amy| last12 = Duane| first12 = Therese M.| title = Timing and type of surgical treatment of Clostridium difficile-associated disease: a practice management guideline from the Eastern Association for the Surgery of Trauma| journal = The Journal of Trauma and Acute Care Surgery| date = 2014-06| pmid = 24854320}}</ref>


* 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>
===American Society of Colon and Rectal Surgeons (ASCRS)===
* Practice Parameters for the Management of ''Clostridium difficile'' Infection (2015)<ref>{{Cite journal| doi = 10.1097/DCR.0000000000000289| issn = 1530-0358| volume = 58| issue = 1| pages = 10–24| last1 = Steele| first1 = Scott R.| last2 = McCormick| first2 = James| last3 = Melton| first3 = Genevieve B.| last4 = Paquette| first4 = Ian| last5 = Rivadeneira| first5 = David E.| last6 = Stewart| first6 = David| last7 = Buie| first7 = W. Donald| last8 = Rafferty| first8 = Janice| title = Practice parameters for the management of Clostridium difficile infection| journal = Diseases of the Colon and Rectum| date = 2015-01| pmid = 25489690}}</ref>


===Management of CDI in IBD Patients===
===European Society of Clinical Microbiology and Infectious Diseases (ESCMID)===
* 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.
* Update of the Treatment Guidance Document for ''Clostridium difficile'' Infection (2014)<ref>{{Cite journal| doi = 10.1111/1469-0691.12418| issn = 1469-0691| volume = 20 Suppl 2| pages = 1–26| last1 = Debast| first1 = S. B.| last2 = Bauer| first2 = M. P.| last3 = Kuijper| first3 = E. J.| last4 = European Society of Clinical Microbiology and Infectious Diseases| title = European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection| journal = Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases| date = 2014-03| pmid = 24118601}}</ref>
* 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==
===American Academy of Pediatrics (AAP)===
* Don't screen for clostridium difficle among patients without diarrhea.
* Policy Statement: Clostridium difficile Infection in Infants and Children (2013)<ref>{{Cite journal| doi = 10.1542/peds.2012-2992| issn = 1098-4275| volume = 131| issue = 1| pages = 196–200| last1 = Schutze| first1 = Gordon E.| last2 = Willoughby| first2 = Rodney E.| last3 = Committee on Infectious Diseases| last4 = American Academy of Pediatrics| title = Clostridium difficile infection in infants and children| journal = Pediatrics| date = 2013-01| pmid = 23277317}}</ref>
* Don't repeat testing for negative tests.
* Dont 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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[[Category:Resident survival guide]]
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Latest revision as of 17:26, 18 September 2017

Clostridium difficile infection

Overview

Diagnostic Criteria

Classification of Disease Severity

Risk Factors

Complete Diagnostic Approach

Management

Dos and Don'ts

Guidelines and Resources

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

Overview

Clostridium difficile infection is the leading cause to nosocomial diarrhea. Clinical presentation ranges across a broad spectrum from asymptomatic carriage, to diarrheal illness, to complicated disease hallmarked by pseudomembranous colitis, toxic megacolon, or bowel perforation. Diagnosis is established by the presence of diarrheal symptoms coupled with positive stool tests or endoscopic findings. Therapeutic approach and antibiotic choice should be stratified according to severity of disease and risk of recurrence.

Diagnostic Criteria

Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)

The diagnosis of C. difficile infection should be based on a combination of clinical and laboratory findings. A case definition for the usual presentation includes the following findings:[1]

  • The presence of diarrhea, defined as passage of 3 or more unformed stools in 24 or fewer consecutive hours AND
  • A stool test result positive for the presence of toxigenic C. difficile or its toxins OR colonoscopic or histopathologic findings demonstrating pseudomembranous colitis.

The same criteria should be used to diagnose recurrent C. difficile infection.

European Society of Clinical Microbiology and Infectious Diseases (ESCMID)

Diagnosis of C. difficile infection is based on the following criteria:[2]

  • A combination of signs and symptoms, confirmed by microbiological evidence of C. difficile in stools, in the absence of another cause
    OR
  • Colonoscopic or histopathological findings demonstrating pseudomembranous colitis

Diagnostic tests for C. difficile infection include:[3]

Classification of Disease Severity

American College of Gastroenterology (ACG)

Classification of disease severity:[4]

  • Mild disease
Diarrhea as the only symptom
  • Moderate disease
Diarrhea but without additional symptoms/signs meeting the definition of severe or complicated disease
  • Severe disease
Hypoalbuminemia (serum albumin < 3 g/dl) AND
WBC ≥ 15,000 cells/mL OR abdominal tenderness without criteria of complicated disease
  • Complicated disease
Any of the following attributable to C. difficile infection:
Admission to intensive care unit
Hypotension with or without required use of vasopressors
Fever ≥ 38.5°C
Ileus (acute nausea, emesis, sudden cessation of diarrhea, significant abdominal distention, or radiological signs consistent with disturbed intestinal transit)
Mental status changes
WBC ≥ 35,000 cells/mL or < 2,000 cells/mL
Serum lactate levels > 2.2 mmol/l
Any evidence of end organ failure
  • Recurrent disease
Recurrence within 8 weeks of completion of therapy

Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)

Initial episode of C. difficile infection may be stratified by disease severity as follows:[5]

  • Mild-to-moderate disease
Leukocytosis with WBC < 15,000 cells/mL AND serum creatinine < 1.5 times the premorbid level
  • Severe disease
Leukocytosis with WBC ≥ 15,000 cells/mL OR serum creatinine ≥ 1.5 times the premorbid level
  • Severe, complicated disease
Hypotension or shock, ileus, megacolon

European Society of Clinical Microbiology and Infectious Diseases (ESCMID)

Severe disease is defined as an episode of C. difficile infection with:[6]

Characteristics that correlate with severity of colitis:[7]

  • Physical examination
Fever (core body temperature > 38.5°C)
Rigors (uncontrollable shaking and a feeling of cold followed by a rise in body temperature)
Hemodynamic instability including signs of distributive shock
Respiratory failure requiring mechanical ventilation
Signs and symptoms of peritonitis
Signs and symptoms of colonic ileus
  • Laboratory investigations
Marked leukocytosis (leukocyte count > 15,000 cells/mL)
Marked left shift (band neutrophils > 20% of leukocytes)
Rise in serum creatinine (> 50% above the baseline)
Elevated serum lactate (≥ 5 mmol/L)
Markedly reduced serum albumin (< 3 mg/dl)
Pseudomembranous colitis
  • Imaging
Distention of large intestine (> 6 cm in transverse width of colon)
Colonic wall thickening including low-attenuation mural thickening
Pericolonic fat stranding
Ascites not explained by other causes

Risk Factors

The most important risk factor remains antibiotic use. Other established risk factors include:[8]

Use of the following antibiotics has been associated with C. difficile infection:[9]

  • Very common
Clindamycin
Ampicillin
Amoxicillin
Cephalosporins
Fluoroquinolones
  • Somewhat common
Penicillins
Sulfonamides
Trimethoprim
Trimethoprim-Sulfamethoxazole
Macrolides
  • Uncommon
Aminoglycosides
Bacitracin
Metronidazole
Teicoplanin
Rifampin
Chloramphenicol
Tetracyclines
Carbapenems
Daptomycin
Tigecycline

Complete Diagnostic Approach

Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CBC, complete blood count; DC, differential count; EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; NAAT, nucleic acid amplification test; PCR, polymerase chain reaction; SMA-7, sequential multiple analysis-7.

Clostridium difficile Infection

  • Diarrhea (passage of 3 or more unformed stools in ≤ 24 hours) with microbiological evidence of C. difficile
  • Colonoscopic or histopathological findings demonstrating pseudomembranous colitis
 
 
 
 
 
 
 
 

Focused History

  • Characterize the symptoms:
  • Other relevant history:
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Other Investigation

Positive results of either EIA or NAAT should prompt treatment.

  • GDH (high sensitivity, low specificity): screening test
  • EIA for toxins (low sensitivity, high specificity): confirmatory test
  • NAAT (high sensitivity, high specificity): standard diagnostic test
 
 

Management

Asymptomatic carrier

  • No treatment indicated

Mild disease

Close outpatient monitoring without the administration of antibiotics

Moderate disease

  • Consideration of hospitalization AND
  • Cessation of predisposing antibiotics AND
  • Hydration AND
  • Monitoring of clinical status AND
  • Administration of metronidazole (500 mg three times per day)
    OR
Administration of vancomycin (125 mg orally four times per day for 14 days)

Severe disease

  • Hospitalization AND
  • Oral or nasogastric vancomycin (500 mg four times per day) with or without intravenous metronidazole (500 mg three times per day)
    OR
Oral fidaxomicin (200 mg twice a day for 10 days) if the risk of recurrence is high

Complicated disease

First recurrence

  • Oral vancomycin (125 mg four times per day for 14 days)
    OR
Oral fidaxomicin (200 mg twice a day for 10 days)

Second or further recurrence

Dos and Don'ts

Dos

Don'ts

  • Do NOT test for C. difficile in a patient without diarrhea.
  • Do NOT repeat test if the results are negative.
  • Do NOT perform test of microbiological cure.
  • Do NOT treat asymptomatic carriage.
  • Do NOT administer antiperistaltic agents to patients with suspected or confirmed C. difficile infection.

Guidelines and Resources

Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)

  • Strategies to Prevent Clostridium difficile Infections in Acute Care Hospitals (2014)[11]
  • Clinical Practice Guidelines for Clostridium difficile Infection in Adults (2010)[12]

American College of Gastroenterology (ACG)

  • Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections (2013)[13]

Association for Professionals in Infection Control and Epidemiology (APIC)

  • Preventing Clostridium difficile infections (2011)[14]

Eastern Association for the Surgery of Trauma (EAST)

  • Timing and type of surgical treatment of Clostridium difficile-associated disease (2014)[15]

American Society of Colon and Rectal Surgeons (ASCRS)

  • Practice Parameters for the Management of Clostridium difficile Infection (2015)[16]

European Society of Clinical Microbiology and Infectious Diseases (ESCMID)

  • Update of the Treatment Guidance Document for Clostridium difficile Infection (2014)[17]

American Academy of Pediatrics (AAP)

  • Policy Statement: Clostridium difficile Infection in Infants and Children (2013)[18]

References

  1. Cohen, Stuart H.; Gerding, Dale N.; Johnson, Stuart; Kelly, Ciaran P.; Loo, Vivian G.; McDonald, L. Clifford; Pepin, Jacques; Wilcox, Mark H.; Society for Healthcare Epidemiology of America; Infectious Diseases Society of America (2010-05). "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)". Infection Control and Hospital Epidemiology. 31 (5): 431–455. doi:10.1086/651706. ISSN 1559-6834. PMID 20307191. Check date values in: |date= (help)
  2. Debast, S. B.; Bauer, M. P.; Kuijper, E. J.; European Society of Clinical Microbiology and Infectious Diseases (2014-03). "European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection". Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 20 Suppl 2: 1–26. doi:10.1111/1469-0691.12418. ISSN 1469-0691. PMID 24118601. Check date values in: |date= (help)
  3. Debast, S. B.; Bauer, M. P.; Kuijper, E. J.; European Society of Clinical Microbiology and Infectious Diseases (2014-03). "European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection". Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 20 Suppl 2: 1–26. doi:10.1111/1469-0691.12418. ISSN 1469-0691. PMID 24118601. Check date values in: |date= (help)
  4. Surawicz, Christina M.; Brandt, Lawrence J.; Binion, David G.; Ananthakrishnan, Ashwin N.; Curry, Scott R.; Gilligan, Peter H.; McFarland, Lynne V.; Mellow, Mark; Zuckerbraun, Brian S. (2013-04). "Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections". The American Journal of Gastroenterology. 108 (4): 478–498, quiz 499. doi:10.1038/ajg.2013.4. ISSN 1572-0241. PMID 23439232. Check date values in: |date= (help)
  5. Cohen, Stuart H.; Gerding, Dale N.; Johnson, Stuart; Kelly, Ciaran P.; Loo, Vivian G.; McDonald, L. Clifford; Pepin, Jacques; Wilcox, Mark H.; Society for Healthcare Epidemiology of America; Infectious Diseases Society of America (2010-05). "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)". Infection Control and Hospital Epidemiology. 31 (5): 431–455. doi:10.1086/651706. ISSN 1559-6834. PMID 20307191. Check date values in: |date= (help)
  6. Debast, S. B.; Bauer, M. P.; Kuijper, E. J.; European Society of Clinical Microbiology and Infectious Diseases (2014-03). "European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection". Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 20 Suppl 2: 1–26. doi:10.1111/1469-0691.12418. ISSN 1469-0691. PMID 24118601. Check date values in: |date= (help)
  7. Debast, S. B.; Bauer, M. P.; Kuijper, E. J.; European Society of Clinical Microbiology and Infectious Diseases (2014-03). "European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection". Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 20 Suppl 2: 1–26. doi:10.1111/1469-0691.12418. ISSN 1469-0691. PMID 24118601. Check date values in: |date= (help)
  8. Khanna, Sahil; Pardi, Darrell S. (2012-11). "Clostridium difficile infection: new insights into management". Mayo Clinic Proceedings. 87 (11): 1106–1117. doi:10.1016/j.mayocp.2012.07.016. ISSN 1942-5546. PMC 3541870. PMID 23127735. Check date values in: |date= (help)
  9. Leffler, Daniel A.; Lamont, J. Thomas (2015-04-16). "Clostridium difficile infection". The New England Journal of Medicine. 372 (16): 1539–1548. doi:10.1056/NEJMra1403772. ISSN 1533-4406. PMID 25875259.
  10. Leffler, Daniel A.; Lamont, J. Thomas (2015-04-16). "Clostridium difficile infection". The New England Journal of Medicine. 372 (16): 1539–1548. doi:10.1056/NEJMra1403772. ISSN 1533-4406. PMID 25875259.
  11. Dubberke, Erik R.; Carling, Philip; Carrico, Ruth; Donskey, Curtis J.; Loo, Vivian G.; McDonald, L. Clifford; Maragakis, Lisa L.; Sandora, Thomas J.; Weber, David J.; Yokoe, Deborah S.; Gerding, Dale N. (2014-09). "Strategies to prevent Clostridium difficile infections in acute care hospitals: 2014 update". Infection Control and Hospital Epidemiology. 35 Suppl 2: –48-65. ISSN 1559-6834. PMID 25376069. Check date values in: |date= (help)
  12. Cohen, Stuart H.; Gerding, Dale N.; Johnson, Stuart; Kelly, Ciaran P.; Loo, Vivian G.; McDonald, L. Clifford; Pepin, Jacques; Wilcox, Mark H.; Society for Healthcare Epidemiology of America; Infectious Diseases Society of America (2010-05). "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)". Infection Control and Hospital Epidemiology. 31 (5): 431–455. doi:10.1086/651706. ISSN 1559-6834. PMID 20307191. Check date values in: |date= (help)
  13. Surawicz, Christina M.; Brandt, Lawrence J.; Binion, David G.; Ananthakrishnan, Ashwin N.; Curry, Scott R.; Gilligan, Peter H.; McFarland, Lynne V.; Mellow, Mark; Zuckerbraun, Brian S. (2013-04). "Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections". The American Journal of Gastroenterology. 108 (4): 478–498, quiz 499. doi:10.1038/ajg.2013.4. ISSN 1572-0241. PMID 23439232. Check date values in: |date= (help)
  14. Rebmann, Terri; Carrico, Ruth M.; Association for Professionals in Infection Control and Epidemiology, null (2011-04). "Preventing Clostridium difficile infections: an executive summary of the Association for Professionals in Infection Control and Epidemiology's elimination guide". American Journal of Infection Control. 39 (3): 239–242. doi:10.1016/j.ajic.2010.10.011. ISSN 1527-3296. PMID 21371783. Check date values in: |date= (help)
  15. Ferrada, Paula; Velopulos, Catherine G.; Sultan, Shahnaz; Haut, Elliott R.; Johnson, Emily; Praba-Egge, Anita; Enniss, Toby; Dorion, Heath; Martin, Niels D.; Bosarge, Patrick; Rushing, Amy; Duane, Therese M. (2014-06). "Timing and type of surgical treatment of Clostridium difficile-associated disease: a practice management guideline from the Eastern Association for the Surgery of Trauma". The Journal of Trauma and Acute Care Surgery. 76 (6): 1484–1493. doi:10.1097/TA.0000000000000232. ISSN 2163-0763. PMID 24854320. Check date values in: |date= (help)
  16. Steele, Scott R.; McCormick, James; Melton, Genevieve B.; Paquette, Ian; Rivadeneira, David E.; Stewart, David; Buie, W. Donald; Rafferty, Janice (2015-01). "Practice parameters for the management of Clostridium difficile infection". Diseases of the Colon and Rectum. 58 (1): 10–24. doi:10.1097/DCR.0000000000000289. ISSN 1530-0358. PMID 25489690. Check date values in: |date= (help)
  17. Debast, S. B.; Bauer, M. P.; Kuijper, E. J.; European Society of Clinical Microbiology and Infectious Diseases (2014-03). "European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection". Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 20 Suppl 2: 1–26. doi:10.1111/1469-0691.12418. ISSN 1469-0691. PMID 24118601. Check date values in: |date= (help)
  18. Schutze, Gordon E.; Willoughby, Rodney E.; Committee on Infectious Diseases; American Academy of Pediatrics (2013-01). "Clostridium difficile infection in infants and children". Pediatrics. 131 (1): 196–200. doi:10.1542/peds.2012-2992. ISSN 1098-4275. PMID 23277317. Check date values in: |date= (help)