Clostridioides difficile
One-Sentence Definition
Clostridioides difficile is a spore-forming, toxin-producing anaerobic Gram-positive bacillus that causes antibiotic-associated diarrhoea and colitis when the gut microbiota is disrupted.
Taxonomy & Morphology
- Gram-positive bacillus, obligate anaerobe, forms endospores (formerly Clostridium difficile)
- Spores survive alcohol, drying, and most routine disinfectants — the key control problem
Virulence Highlights
- Toxin A (TcdA) and Toxin B (TcdB) — glucosylate Rho GTPases → cytoskeletal collapse, tight-junction loss, inflammation
- Binary toxin (CDT) in hypervirulent lineages (e.g., ribotype 027) associated with more severe disease
- Toxin production is regulated by tcdC and nutrient sensing; carriage without toxin production is common and should not be treated
Pathogenesis
Antibiotic exposure destroys colonization resistance in the Human Microbiome — particularly the loss of secondary bile acid production — allowing spore germination and outgrowth. Highest-risk agents: clindamycin, fluoroquinolones, and broad-spectrum cephalosporins.
Clinical Syndromes
- Watery diarrhoea with abdominal pain and leukocytosis
- Pseudomembranous colitis on endoscopy
- Severe: toxic megacolon, perforation, ileus (diarrhoea may stop — a dangerous sign)
- Recurrence in ~20–25% after a first episode, rising with each recurrence
Diagnosis
Two-step algorithm, and only test diarrhoeal stool
A sensitive screen (GDH antigen or PCR for tcdB) followed by a specific toxin EIA. NAAT alone cannot distinguish colonization from disease, so testing formed stool generates false “cases” and unnecessary treatment — a classic diagnostic stewardship failure.
Treatment
- Oral vancomycin or fidaxomicin first-line; metronidazole now reserved for resource-limited settings
- Stop the inciting antibiotic where possible
- Recurrent disease: fidaxomicin, bezlotoxumab, or faecal microbiota transplantation — high efficacy for multiply recurrent infection
Infection Control
Alcohol hand rub does not kill spores
Soap and water plus contact precautions and a sporicidal (chlorine-based) environmental agent. See Infection Prevention and Control.
AMR / Stewardship Relevance
C. difficile rate is a standard outcome metric for Antimicrobial Stewardship programmes — it measures the collateral damage of antibiotic use rather than resistance itself.
Related MOCs
- MOC - Bacteriology · MOC - Clinical Microbiology · MOC - Diseases by System · MOC - Public Health & Epidemiology
Active Recall Questions
- Why is testing formed stool for C. difficile harmful?
- Which microbiota function is lost that permits germination?
- Why is alcohol gel inadequate here?