87493

Infectious agent detection by nucleic acid (DNA or RNA); Clostridioides difficile, toxin gene(s), amplified probe technique

CPT code 87493 describes a highly sensitive laboratory procedure used to identify the presence of toxigenic Clostridioides difficile (formerly known as Clostridium difficile) in a patient's stool specimen. Specifically, this code is utilized when the laboratory employs a nucleic acid amplification test (NAAT), such as polymerase chain reaction (PCR), to detect the specific toxin-producing genes of C. difficile. Clostridioides difficile is a gram-positive, spore-forming, anaerobic bacillus that is a leading cause of healthcare-associated infectious diarrhea and pseudomembranous colitis. The pathogenesis of C. difficile infection (CDI) is primarily driven by the production of two main exotoxins: Toxin A (an enterotoxin) and Toxin B (a cytotoxin), and sometimes a binary toxin. Since not all strains of C. difficile produce these toxins, merely detecting the presence of the organism via standard culture is insufficient for diagnosing an active, pathogenic infection. The amplified probe technique detailed in code 87493 addresses this limitation by specifically targeting and amplifying the genetic sequences (such as tcdA and tcdB genes) that code for these toxins, confirming that the strain present in the patient's gastrointestinal tract has the pathogenic potential to cause CDI. The procedure begins with the collection of an unformed or liquid stool sample, which is a critical clinical requirement since testing formed stool frequently leads to the detection of asymptomatic colonization rather than active disease. Once the specimen arrives at the laboratory, nucleic acids (DNA) are extracted from the complex stool matrix. The extracted DNA is then subjected to an amplification process utilizing sequence-specific primers and fluorescently labeled probes. As the target toxin genes are exponentially amplified, the probes emit a fluorescent signal that is measured in real-time by the testing instrument. A positive result indicates the presence of toxigenic C. difficile, which, when correlated with clinical symptoms like new-onset frequent unformed bowel movements, abdominal pain, and leukocytosis, firmly establishes the diagnosis of CDI. This NAAT approach is highly favored for its rapid turnaround time and superior sensitivity compared to traditional toxigenic culture or enzyme immunoassays (EIA), though it is often used as part of a multi-step testing algorithm to maximize both sensitivity and specificity in clinical diagnosis.

Clinical Indications

  • New onset of clinically significant, unformed diarrhea (typically defined as 3 or more unformed stools in 24 hours) with no other recognized cause.
  • Suspected healthcare-associated or antibiotic-associated diarrhea.
  • Suspected pseudomembranous colitis or toxic megacolon.
  • Leukocytosis or severe abdominal pain in a patient with a history of recent broad-spectrum antibiotic use or recent hospitalization.
  • As part of a multi-step testing algorithm for C. difficile infection (CDI) when an initial enzyme immunoassay (EIA) for GDH is positive but the EIA for toxins A/B is negative.
  • Evaluation of a patient presenting with unformed stool and a history of previous C. difficile infection to determine if toxigenic strains are present in the setting of suspected recurrence.

Procedure Steps

  1. Collection of an unformed or liquid stool specimen from the patient in a sterile, leak-proof container.
  2. Transport of the specimen to the laboratory under appropriate temperature controls to prevent degradation of nucleic acids.
  3. Preparation of the stool sample, which may involve dilution and the addition of lysis buffers to disrupt bacterial cell walls and release intracellular contents.
  4. Extraction and purification of nucleic acids (DNA) from the stool matrix to remove inhibitors that could interfere with the amplification process.
  5. Preparation of the master mix containing DNA polymerase, nucleotides, sequence-specific primers targeting C. difficile toxin genes (e.g., tcdB), and fluorescently labeled probes.
  6. Loading the extracted DNA and master mix into a thermocycler or automated real-time PCR platform.
  7. Execution of thermal cycling to repeatedly denature the DNA, anneal the primers/probes, and extend the newly synthesized DNA strands.
  8. Real-time detection and measurement of the fluorescent signal emitted during the amplification of the target toxin genes.
  9. Data analysis by the laboratory software to determine if the fluorescent signal exceeds the established threshold for a positive result.
  10. Generation of a clinical laboratory report indicating the presence or absence of toxigenic C. difficile DNA in the specimen.

Coding Guidelines

  • Report 87493 only once per day per specimen, regardless of whether one or multiple toxin genes (e.g., Toxin A and Toxin B) are targeted.
  • Do not use this code for enzyme immunoassay (EIA) detection of C. difficile toxins; use 87324 instead.
  • Do not use this code for the detection of glutamate dehydrogenase (GDH) antigen; use 87324 for EIA GDH testing.
  • Testing should typically only be performed on unformed (liquid or soft) stool specimens, unless the patient has suspected ileus or toxic megacolon.
  • This code should not be billed for 'test-of-cure' purposes, as NAAT can remain positive for weeks or months after successful clinical resolution of CDI.
  • Ensure appropriate modifier use (e.g., modifier 59 or 91) if repeat testing is medically necessary and performed on separate specimens on the same day, though this is clinically rare.

Associated ICD-10 Codes