What are the classifications of Clostridioides difficile (C. diff)?

From the Guidelines

Clostridium difficile (C. diff) infections are classified into three main categories based on severity: mild to moderate, severe, and severe, complicated (previously called fulminant), with classifications also considering the occurrence pattern: initial episode, recurrent, or refractory. The classification of C. diff infections is crucial for determining the appropriate treatment strategy and predicting outcomes. According to the 2010 Society for Healthcare Epidemiology of America and Infectious Disease Society of America Clinical Practice Guidelines, as mentioned in 1, mild CDI is categorized as WBC < 15 X 10^9/L and serum creatinine < 1.5 times premorbid level, while severe CDI is defined as WBC ≥ 15 X 10^9/L, or serum creatinine ≥ 1.5 times premorbid level. Severe, complicated CDI is characterized by hypotension, shock, ileus, or megacolon, as noted in 1 and 1. Key findings that distinguish severe CDI include WBC >15 X 10^9/L, serum albumin <30 g/L, and an increase in serum creatinine level ≥1.5 times premorbid level, as outlined in 1. Understanding these classifications is essential for guiding treatment decisions, such as the use of oral vancomycin, fidaxomicin, or metronidazole, and considering more aggressive interventions like fecal microbiota transplantation for recurrent cases, as implied by the treatment strategies discussed in 1 and 1. Some studies propose risk scoring systems to predict the risk of fulminant CDI, including factors such as age, WBC count, and cardiorespiratory failure, as seen in 1. However, the most recent and highest quality evidence, as presented in 1, provides a clear classification system based on disease severity, which is essential for clinical decision-making. The occurrence pattern of C. diff infections, including initial episode, recurrent (return of symptoms within 8 weeks after successful treatment), or refractory (persistent symptoms despite appropriate therapy), also plays a critical role in determining the treatment approach, as noted in 1. In clinical practice, it is essential to consider these classifications and occurrence patterns to provide optimal care and improve patient outcomes, as supported by the evidence presented in 1 and 1.

From the FDA Drug Label

CDAD was classified as severe (defined as 10 or more unformed bowel movements per day or WBC ≥15000/mm3) in 25% of subjects, and 47% were previously treated for CDAD

• The classification of C. difficile (CDAD) is based on the following criteria:
  • Severe: 10 or more unformed bowel movements per day or WBC ≥15000/mm3
  • Non-severe: less than 10 unformed bowel movements per day and WBC <15000/mm3
  • BI strain, non-BI strain, and unknown strain are also used to classify C. difficile isolates 2 2

From the Research

Classification of Cdiff

The classification of Clostridioides difficile (Cdiff) can be based on several factors, including:

• Toxin production: Cdiff strains can produce various toxins, including toxin A (TcdA), toxin B (TcdB), and binary toxin (CDT) 3, 4, 5
• Ribotyping: Cdiff strains can be classified into different ribotypes, such as ribotype 027, which is considered hypervirulent 6, 7
• Molecular typing: Various molecular typing methods, including PCR-based methods, restriction endonuclease analysis, and pulse field gel electrophoresis, can be used to classify Cdiff strains 6
• Disease severity: Cdiff strains can be classified based on their association with disease severity, with some strains, such as those producing binary toxin, being associated with worse disease outcomes 7

Toxin Production

Cdiff strains can produce various toxins, including:

• Toxin A (TcdA): a large clostridial glucosylating toxin that acts on the colonic epithelium and immune cells 3, 5
• Toxin B (TcdB): a large clostridial glucosylating toxin that acts on the colonic epithelium and immune cells 3, 5
• Binary toxin (CDT): a toxin that exhibits ADP ribosyltransferase activity and is produced by some Cdiff strains 3, 4, 7

Clinical Relevance

The classification of Cdiff is important for understanding the clinical relevance of different strains, including:

• Disease severity: some Cdiff strains, such as those producing binary toxin, are associated with worse disease outcomes 7
• Treatment outcomes: the classification of Cdiff can inform treatment decisions and outcomes 4, 5
• Epidemiology: the classification of Cdiff can inform our understanding of the epidemiology of Cdiff infections, including transmission and outbreaks 6, 7