Clostridium difficile infection laboratory findings

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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

• Hypokalemia
• Hyponatremia
• Metabolic acidosis (low bicarbonate)

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

• Coagulation profile, such as PTT, PT, and INR should be ready because surgery may be required among patients with complicated disease.

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 enzyme-linked immunoabsorbant assay (ELISA) for toxin A or B (or both) is generally sensitive and specific:
  • Sensitivity 63-99%
  • 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

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  Blood agar, cycloserine mannitol plate culture growing colonies of Clostridium difficile for 48 hours. From Public Health Image Library (PHIL).

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  Clostridium difficile colonies after 48hrs growth on a blood agar plate; Magnified 4.8X. From Public Health Image Library (PHIL).

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  Gram-stain micrograph depicts Clostridium difficile after 24hrs of growth in chopped meat medium; Magnified 956X. From Public Health Image Library (PHIL).

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  Clostridium difficile colonies grown on cycloserine mannitol agar after 48 hours. From Public Health Image Library (PHIL).

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  Impression smear photomicrograph of Clostridium difficile bacteria grown on cycloserine mannitol blood agar. From Public Health Image Library (PHIL).

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  Micrograph of the bacterium Clostridium difficile is made from an impression smear of 72hr anaerobe blood agar. From Public Health Image Library (PHIL).

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  Petri dish culture plate had contained Cycloserine Cefoxitin Fructose Agar (CCFA), inoculated with a Clostridium difficile bacterial culture. From Public Health Image Library (PHIL).