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{{Clostridium difficile}}
{{Siren|Clostridium difficile infection}}
{{CMG}}
{{Clostridium difficile infection}}
{{CMG}}; {{AE}} {{YD}}


==Laboratory Findings==
== Overview ==
===Cytotoxicity assay===
Testing is generally not necessarily for patients with formed stools (no diarrhea). The gold standard for diagnosis of ''C. difficile ''infection is cell culture cytotoxic assay, but it is rarely used clinically (difficult technique and time consuming). Among patients with diarrhea,''C. difficil''e infection is diagnosed either by [[enzyme immunoassay]] ([[ELISA]]) for toxins A and/or B in stools or by [[DNA-based test]]s ([[PCR]]) that detect bacterial toxin genes in stools. Although both ELISA and DNA-based tests may be performed sequentially, only one positive test is sufficient to diagnose ''C. difficile'' infection. Both ELISA and DNA-based tests also have a high [[negative predictive value]] > 95% among average-risk patients, and generally negative results warrants the search for alternative diagnoses. The advantage of DNA-based tests over ELISA is that it may detect the presence of [[BI/NAP1/027]] strain, which alters the management plan. However, DNA-based tests may also detect clinically irrelevant findings that may delay the diagnosis. Stool culture requires [[anaerobic]] culture and may not be available. Although not diagnostic, additional blood testing may be necessary to monitor for possible development of complications or the success/failure of antimicrobial therapy.
''C. difficile'' toxin detection as cytopathic effect in cell culture, and neutralized with specific anti-sera is the practical gold standard for studies investigating new CDAD diagnostic techniques. Toxigenic culture, in which organisms are cultured on selective medium and tested for toxin production remains the [[Gold standard (test)|gold standard]] and is the most sensitive and specific test, although it is slow and labour-intensive.<ref name=Murray_1993>{{cite book | author = Murray PR, Baron EJ, Pfaller EA, Tenover F, Yolken RH (editors) |title = Manual of Clinical Microbiology | edition = 8th ed | publisher=ASM Press | location = Washington DC | date = 2003 | isbn = 1-55581-255-3}}</ref>


===Enzyme-linked immunoabsorbant assay (ELISA) for toxin===
== Laboratory Findings ==
Assessment of the A and B toxins by [[ELISA|enzyme-linked immunoabsorbant assay]] (ELISA) for toxin A or B (or both) has:
Testing is generally not necessarily for patients with formed stools (no diarrhea). Among patients with diarrhea, ''C. difficile'' infection is diagnosed either by enzyme immunoassay (ELISA) for toxins A and/or B in stools or by DNA-based tests that detect bacterial toxin genes in stools. Although not diagnostic, additional blood testing may be necessary to monitor for possible development of complications or the success/failure of antimicrobial therapy.
* [[sensitivity (tests)|Sensitivity]] 63-99%
* [[specificity (tests)|Specificity]] 93-100%


At a prevalence of 15%, this leads to:
== Blood Work-Up ==
* [[Positive predictive value]] 73%
* [[Negative predictive value]] 96%


Experts recommend sending as many as three samples to rule-out disease if initial tests are negative. ''C. difficile'' toxin should clear from the stool of previously infected patients if treatment is effective.
=== Complete Blood Count With Differential ===
* [[Leukocytosis]] with left shift. Leukocytosis > 20,000 cells/mL is suggestive of severe/complicated ''C. difficile'' infection.
* [[Leucopenia]] is occasionally reported. Leukopenia < 2,000 cells/mL is suggestive of severe/complicated ''C. difficile'' infection.


Unfortunately, many hospitals only test for the prevalent toxin A. Strains that express only the B toxin are now present in many hospitals and ordering both toxins should occur. Not testing for both may contribute to a delay in obtaining laboratory results, which is often the cause of prolonged illness and poor outcomes.
=== Electrolytes ===
* [[Hypokalemia]]
* [[Hyponatremia]]
* [[Metabolic acidosis]] (low [[bicarbonate]])


===Other Stool Tests===
=== Inflammatory Markers ===
Stool [[leukocyte]] measurements and stool [[lactoferrin]] levels have also been proposed as diagnostic tests, but may have limited diagnostic accuracy.<ref name=Vaishnavi_2000>{{cite journal |author=Vaishnavi C, Bhasin D, Kochhar R, Singh K |title=Clostridium difficile toxin and faecal lactoferrin assays in adult patients |journal=Microbes Infect |volume=2 |issue=15 |pages=1827-30 |year=2000 |pmid=11165926}}</ref>
Inflammatory markers, such as [[CRP]] or [[ESR]] may be helpful for follow-up of patients with ''C. difficile'' infection or a non-specific means to monitor the success of antimicrobial therapy.


===Routine Laboratory Findings===
=== Coagulation Profile ===
* [[Leukocytosis]] up to 40,000 mm3
* [[Coagulation profile]], such as [[PTT]], [[PT]], and [[INR]] should be ready because surgery may be required among patients with complicated disease.
* [[Metabolic acidosis]]


=== Albumin ===
* [[Hypoalbuminemia]]
=== Lactate ===
* Elevated lactate concentration > 2.2 mmol/L may be suggestive of severe/complicated ''C. difficile'' infection.
== Stool Work-Up ==
=== Stool Analysis ===
* [[Leukocytosis]]
* Blood in stools
===Enzyme-Linked Immunoabsorbant Assay (ELISA) for Toxin===
* Assessment of the A and B toxins by [[ELISA|enzyme-linked immunoabsorbant assay]] (ELISA) for toxin A or B (or both) is generally sensitive and specific:
** [[sensitivity (tests)|Sensitivity]] 63-99%
** [[specificity (tests)|Specificity]] 93-100%
* [[Negative predictive value]] > 95% for patients with average risk (generally if ELISA negative, search for alternative diagnoses warranted)
* Following successful antimicrobial therapy, patients may remain positive for many weeks/months. No additional treatment recommended.
* ELISA and DNA-based tests (below) may be used sequentially, but one positive result is sufficient for diagnosis.
=== DNA-Based Tests (PCR) ===
* Higher sensitivity and specificity than ELISA
* Negative predictive value > 95% for patients with average risk (generally if DNA-based tests negative, search for alternative diagnoses warranted)
* Identify microbial toxin genes and toxicogenic strains in unformed stools
* Detects presence of BI/NAP1/027 strain
* May detect clinically irrelevant findings.
* Following successful antimicrobial therapy, patients may remain positive for many weeks/months. No additional treatment recommended.
* DNA-based tests and ELISA (above) may be used sequentially, but one positive result is sufficient for diagnosis.
=== Cell Culture Cytotoxicity Assay ===
* It is the gold standard for the diagnosis of'' C. difficile'' infection.
* Among patients with positive results, fibroblast cell rounding will be observed when cultured cells are added to prepared stools.
* Requires 24-48 hours for results to be positive and is generally not routinely performed.
=== Stool Culture ===
* [[Anaerobic]] culture needed.
* Not widely available.
==Gallery==
<gallery>
Image: Clostridium difficile14.jpeg| Blood agar, cycloserine mannitol plate culture growing colonies of Clostridium difficile for 48 hours. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Clostridium difficile13.jpeg| Clostridium difficile colonies after 48hrs growth on a blood agar plate; Magnified 4.8X. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Clostridium difficile12.jpeg| Gram-stain micrograph depicts Clostridium difficile after 24hrs of growth in chopped meat medium; Magnified 956X. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Clostridium difficile11.jpeg| Clostridium difficile colonies grown on cycloserine mannitol agar after 48 hours. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Clostridium difficile10.jpeg| Impression smear photomicrograph of Clostridium difficile bacteria grown on cycloserine mannitol blood agar. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Clostridium difficile08.jpeg| Micrograph of the bacterium Clostridium difficile is made from an impression smear of 72hr anaerobe blood agar. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Clostridium difficile01.jpeg| Petri dish culture plate had contained Cycloserine Cefoxitin Fructose Agar (CCFA), inoculated with a Clostridium difficile bacterial culture. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
</gallery>
==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
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[[Category:Gastroenterology]]
[[Category:Gastroenterology]]
[[Category:Needs overview]]
[[Category:Needs overview]]
[[Category:Infectious disease]]
 
[[Category:Bacterial diseases]]
[[Category:Bacterial diseases]]


{{WH}}
{{WH}}
{{WS}}
{{WS}}

Latest revision as of 17:26, 18 September 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.

Overview

Testing is generally not necessarily for patients with formed stools (no diarrhea). The gold standard for diagnosis of C. difficile infection is cell culture cytotoxic assay, but it is rarely used clinically (difficult technique and time consuming). Among patients with diarrhea,C. difficile infection is diagnosed either by enzyme immunoassay (ELISA) for toxins A and/or B in stools or by DNA-based tests (PCR) that detect bacterial toxin genes in stools. Although both ELISA and DNA-based tests may be performed sequentially, only one positive test is sufficient to diagnose C. difficile infection. Both ELISA and DNA-based tests also have a high negative predictive value > 95% among average-risk patients, and generally negative results warrants the search for alternative diagnoses. The advantage of DNA-based tests over ELISA is that it may detect the presence of BI/NAP1/027 strain, which alters the management plan. However, DNA-based tests may also detect clinically irrelevant findings that may delay the diagnosis. Stool culture requires anaerobic culture and may not be available. Although not diagnostic, additional blood testing may be necessary to monitor for possible development of complications or the success/failure of antimicrobial therapy.

Laboratory Findings

Testing is generally not necessarily for patients with formed stools (no diarrhea). Among patients with diarrhea, C. difficile infection is diagnosed either by enzyme immunoassay (ELISA) for toxins A and/or B in stools or by DNA-based tests that detect bacterial toxin genes in stools. Although not diagnostic, additional blood testing may be necessary to monitor for possible development of complications or the success/failure of antimicrobial therapy.

Blood Work-Up

Complete Blood Count With Differential

  • Leukocytosis with left shift. Leukocytosis > 20,000 cells/mL is suggestive of severe/complicated C. difficile infection.
  • Leucopenia is occasionally reported. Leukopenia < 2,000 cells/mL is suggestive of severe/complicated C. difficile infection.

Electrolytes

Inflammatory Markers

Inflammatory markers, such as CRP or ESR may be helpful for follow-up of patients with C. difficile infection or a non-specific means to monitor the success of antimicrobial therapy.

Coagulation Profile

Albumin

Lactate

  • Elevated lactate concentration > 2.2 mmol/L may be suggestive of severe/complicated C. difficile infection.

Stool Work-Up

Stool Analysis

Enzyme-Linked Immunoabsorbant Assay (ELISA) for Toxin

  • Negative predictive value > 95% for patients with average risk (generally if ELISA negative, search for alternative diagnoses warranted)
  • Following successful antimicrobial therapy, patients may remain positive for many weeks/months. No additional treatment recommended.
  • ELISA and DNA-based tests (below) may be used sequentially, but one positive result is sufficient for diagnosis.

DNA-Based Tests (PCR)

  • Higher sensitivity and specificity than ELISA
  • Negative predictive value > 95% for patients with average risk (generally if DNA-based tests negative, search for alternative diagnoses warranted)
  • Identify microbial toxin genes and toxicogenic strains in unformed stools
  • Detects presence of BI/NAP1/027 strain
  • May detect clinically irrelevant findings.
  • Following successful antimicrobial therapy, patients may remain positive for many weeks/months. No additional treatment recommended.
  • DNA-based tests and ELISA (above) may be used sequentially, but one positive result is sufficient for diagnosis.

Cell Culture Cytotoxicity Assay

  • It is the gold standard for the diagnosis of C. difficile infection.
  • Among patients with positive results, fibroblast cell rounding will be observed when cultured cells are added to prepared stools.
  • Requires 24-48 hours for results to be positive and is generally not routinely performed.

Stool Culture

  • Anaerobic culture needed.
  • Not widely available.

Gallery

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "Public Health Image Library (PHIL)".

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