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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}}]]
<li>[[{{PAGENAME}}#Dos|{{fontcolor|#F8F8FF|Dos}}]]</li>
<li>[[{{PAGENAME}}#Don'ts|{{fontcolor|#F8F8FF|Don'ts}}]]</li>
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[[{{PAGENAME}}#Guidelines|{{fontcolor|#F8F8FF|Guidelines}}]]
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__NOTOC__
{{CMG}}

==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 of CDI 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>
* 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 CDI.

===European Society of Clinical Microbiology and Infectious Diseases (ESCMID)===
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>
* A combination of signs and symptoms, confirmed by microbiological evidence of ''C. difficile'' in stools, in the absence of another cause {{or2}}
* Colonoscopic or histopathological findings demonstrating pseudomembranous colitis

Diagnostic tests for CDI 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 (EIA): 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==

===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 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 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)
* 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

===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)
: 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

==Risk Factors==
The most important risk factor remains 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>
* 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 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 inhibitors

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>

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==''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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==Focused History==
* Characterize the symptoms:
:* Abdominal discomfort
:* Poor appetite
:* Diarrhea
:* Nausea
:* Vomiting
:* Bloating
:* Belching
:* Flatulence
:* Lack of bowel movement
* Other relevant history:
:* [[{{PAGENAME}}#Risk Factors|Risk factors]]
:* 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 (distended and tympanic abdomen with tenderness, hypoactive bowel sounds)
* Signs of peritonitis (rebound tenderness, abdominal wall rigidity, hypoactive bowel sounds)
* Signs of dehydration (delayed capillary refill, decreased skin turgor, abnormal respiratory pattern)
* Signs of respiratory distress (tachypnea, tachycardia, abnormal breath sounds)
* Signs of multiple organ failure (cool and clammy skin, 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]]
* Consider abdominal CT scan or colonoscopy in severe disease or concurrent IBD
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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
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==Management==






==Dos and Don'ts==

===Dos===
* Inform the laboratory 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 Hartman’s pouch, ileostomy, or 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 antiperistaltic agents to patients with suspected or confirmed ''C. difficile'' infection.

==Guidelines==

===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>

===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>

===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>

===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>

===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>

===European Society of Clinical Microbiology and Infectious Diseases (ESCMID)===
* 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>

===American Academy of Pediatrics (AAP)===
* 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>

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

[[Category:Disease]]
[[Category:Gastroenterology]]
[[Category:Infectious disease]]
[[Category:Medicine]]
[[Category:Resident survival guide]]