Classification of Clostridioides difficile Infection by Severity
Clostridioides difficile infection is classified into three main severity categories: mild-to-moderate, severe, and fulminant (severe-complicated) disease, based on specific clinical and laboratory parameters that directly predict mortality and need for surgical intervention. 1
Severity Classification System
Mild-to-Moderate CDI
- WBC < 15,000 cells/mL 1
- Serum creatinine < 1.5 times baseline 1
- Diarrhea without systemic signs of severe infection 1
- May have mild abdominal pain and cramping 1
Severe CDI
The presence of any one or more of the following criteria defines severe CDI 1:
Laboratory markers:
- WBC ≥ 15,000 cells/mL 1
- Serum creatinine ≥ 1.5 mg/dL or ≥ 50% increase above baseline 1
- Serum albumin < 2.5-3.0 g/dL 1
Clinical features:
- Age > 65 years 1
- Body temperature > 38.5°C 1
- ≥ 10 bowel movements within 24 hours 1
- Severe abdominal pain 1
- Evidence of pseudomembranous colitis on endoscopy 1
- ICU admission required 1
- Presence of active malignancy 1
Fulminant (Severe-Complicated) CDI
This represents life-threatening disease requiring immediate intervention 1:
- Hypotension or shock 1
- End-organ failure 1
- Ileus (absent bowel sounds, vomiting, no stool passage) 1
- Toxic megacolon (colonic distension > 6 cm on imaging) 1
- Colonic perforation 1
- Septic shock requiring vasopressors 1
Important Clinical Considerations
Absence of diarrhea may paradoxically signal progression to fulminant infection due to colonic dysmotility from ileus, particularly in surgical patients 1. This is a critical pitfall—maintain high suspicion for CDI even without diarrhea if other severe features are present 1.
Hypoalbuminemia is particularly significant because human serum albumin binds C. difficile toxins A and B, impairing their cellular internalization; low albumin levels therefore correlate with increased disease severity 1.
Recurrent CDI Definition
- Return of gastrointestinal symptoms due to CDI following initial resolution 1
- Occurs within 8 weeks after discontinuation of treatment 1
- Affects 10-30% of patients after initial therapy 1
Practical Application
Clinicians must use clinical judgment when assessing severity 1. The presence of multiple risk factors increases the likelihood of adverse outcomes including colectomy and death 1. Patients meeting criteria for severe or fulminant disease require escalated therapy with oral vancomycin or fidaxomicin rather than metronidazole, and fulminant cases may require surgical consultation 1.