What is Clostridioides difficile infection?

CDI (C. diff infection, formerly called Clostridium difficile) is a bacterial infection of the colon caused by C. difficile toxins. It occurs when antibiotics disrupt the normal gut microbiome, removing the bacteria that normally prevent C. difficile from growing. C. diff then overgrows, produces toxins (TcdA and TcdB) that damage the colonic lining, causing symptoms ranging from mild watery diarrhoea (3+ loose stools/day) to severe colitis with fever, abdominal pain, and life-threatening complications (toxic megacolon, septicaemia, perforation).

Who is at highest risk?

Risk factors: antibiotic exposure (almost any antibiotic, but highest risk with fluoroquinolones, clindamycin, broad-spectrum cephalosporins); age ≥65 (highest risk group); hospitalisation (especially prolonged); proton pump inhibitors (PPIs — reduce gastric acid that kills C. diff spores); immunosuppression (cancer, organ transplant, IBD on immunosuppressives); prior CDI episode (25-30% recurrence rate).

How is CDI diagnosed?

Two-step testing is recommended: Step 1: GDH (glutamate dehydrogenase) antigen EIA — highly sensitive screen; positive = further testing needed. Step 2: toxin EIA (TcdA/TcdB) — specific for toxigenic strains. OR NAAT (PCR): detects toxin gene presence — very sensitive but may detect colonisation (non-toxin-producing strains) → potential false positives. Clinical correlation: diagnosis should combine positive test + clinical symptoms (≥3 loose stools/24h) + no other cause identified.

First episode (non-severe): fidaxomicin 200mg BD × 10 days (preferred — lower recurrence) or vancomycin 125mg QDS × 10 days. First episode (severe — WBC >15×10⁹/L, creatinine ≥1.5× baseline): vancomycin 125mg QDS × 10 days. Fulminant CDI (hypotension, ileus, toxic megacolon): IV metronidazole + high-dose oral/rectal vancomycin + urgent surgical consultation. First recurrence: fidaxomicin (preferred); bezlotoxumab for high-risk patients. Second+ recurrences: FMT or FDA-approved microbiome therapeutics (Rebyota, Vowst).

Why is alcohol gel ineffective against C. diff?

C. difficile produces spores — dormant, highly resistant forms that can survive on surfaces for months. Unlike vegetative bacteria (which alcohol kills), spores are resistant to alcohol, most disinfectants and desiccation. Alcohol-based hand rubs (ABHR) are widely used in healthcare for most pathogens but do NOT eliminate C. diff spores. Soap and water handwashing physically removes spores from hands. Environmental cleaning must use sodium hypochlorite (bleach) at ≥1,000 ppm. This is why CDI is notoriously difficult to control in hospitals even with good hand hygiene practices.

How does GMJ News cover C. difficile?

GMJ News covers ECDC and WHO CDI data, antibiotic stewardship as prevention, fidaxomicin/vancomycin treatment, FMT and microbiome therapeutics, bezlotoxumab, the alcohol gel limitation (critical clinical message), hypervirulent ribotype 027, and hospital infection control. CDI is directly relevant to PHIG's hospital accreditation and infection prevention programme — where soap-and-water hand hygiene for C. diff is a core standard.

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Clostridioides difficile

GMJ News knowledge hub · last reviewed September 2026 · Georgian Medical Journal

Summary Statistics Glossary GMJ news FAQ Documents Organizations Research

Clostridioides difficile infection (CDI) — caused by toxin-producing strains of C. difficile (a Gram-positive, spore-forming anaerobe) — is the single most common healthcare-associated infection globally, causing an estimated 200,000+ cases and 10,000-30,000 deaths annually in the US alone, predominantly in patients who have received antibiotics (which disrupt the gut microbiome, allowing C. difficile overgrowth) and elderly hospitalised patients (ECDC). The emergence of hypervirulent ribotype 027 (NAP1) and the recurring challenge of relapsing CDI (25-30% of treated patients relapse) — now addressed by faecal microbiota transplantation (FMT, 80-90% efficacy) and new FDA-approved microbiome therapeutics (Rebyota, Vowst) — make C. difficile the defining infection at the intersection of antibiotic stewardship, hospital infection control and the microbiome revolution. Crucially: alcohol gel does NOT kill C. difficile spores — soap and water handwashing is mandatory.

Key messages

#1 hospital-acquired infection globally

Clostridioides difficile (C. diff) infection (CDI) is the most common healthcare-associated infection globally, causing 200,000+ cases and 10,000-30,000 deaths per year in the US alone. The ECDC estimates CDI is responsible for 8,000-12,000 deaths annually in EU hospitals (ECDC).

Antibiotics disrupt gut microbiome — C. diff fills the gap

CDI occurs when antibiotics disrupt the normal gut microbiome, removing colonisation resistance to C. difficile. Almost any antibiotic can trigger CDI — fluoroquinolones, clindamycin and broad-spectrum cephalosporins carry the highest risk.

Alcohol gel does NOT kill C. diff spores

Critically: alcohol-based hand rubs (ABHR) are INEFFECTIVE against C. difficile spores. Soap and water handwashing (physical removal of spores) is mandatory for CDI prevention. Environmental disinfection requires bleach (sodium hypochlorite ≥1,000 ppm). This makes CDI uniquely difficult to control in healthcare settings.

FMT — 80-90% efficacy for recurrent CDI

Faecal microbiota transplantation (FMT) — restoring the gut microbiome by transplanting stool from a healthy donor — achieves 80-90% cure rates for recurrent CDI, dramatically outperforming repeated antibiotics. FDA-approved microbiome therapeutics (Rebyota, Vowst) are now available.

Antibiotic stewardship is the primary prevention

Rational antibiotic prescribing — avoiding unnecessary antibiotics, using narrow-spectrum agents, shortening courses — is the single most important CDI prevention strategy, protecting the gut microbiome from disruption.

Hypervirulent ribotype 027 — more toxin, more severe

NAP1/BI/027 (ribotype 027) — a hypervirulent C. difficile strain producing higher levels of toxin A and B plus binary toxin — has caused major hospital outbreaks globally, with higher rates of severe complications (toxic megacolon, septicaemia, colectomy) and mortality.

Key statistics

200K+

CDI cases/year in the US; 10,000-30,000 deaths

CDC/WHO

8-12K

CDI deaths/year in EU hospitals (ECDC estimate)

ECDC

most common healthcare-associated infection globally

WHO/ECDC

25-30%

of treated CDI patients experience recurrence

ECDC/Lancet

80-90%

FMT efficacy for recurrent CDI

Cochrane/NEJM

efficacy of alcohol hand gel against C. diff spores — use soap + water

WHO/ECDC

C. difficile ribotype distribution and associated severity — EU/US

Source: ECDC. Ribotype 027 causes more severe disease; ribotype 078 increasingly community-associated.

Glossary of key terms

Clostridioides difficile (C. diff)
WHOA Gram-positive, spore-forming, anaerobic bacterium — formerly named Clostridium difficile; reclassified as Clostridioides difficile in 2016. C. diff spores are resistant to alcohol, most disinfectants, heat and desiccation — surviving on hospital surfaces and equipment for months.

TcdA and TcdB toxins
WHO/ResearchTwo major exotoxins: TcdA (enterotoxin) and TcdB (cytotoxin) — both glucosyltransferases that inactivate Rho GTPases in intestinal epithelial cells, disrupting the actin cytoskeleton and causing mucosal damage, fluid secretion and inflammation. Hypervirulent strains also produce binary toxin (CDT) — associated with more severe disease.

Faecal microbiota transplantation (FMT)
FDA/ECDCTransfer of processed stool from a screened, healthy donor into a CDI patient's GI tract (via colonoscopy, enema, or oral capsules) to restore microbiome diversity and colonisation resistance. Achieves 80-90% cure rates for recurrent CDI — dramatically superior to antibiotics alone. FDA-approved microbiome live biotherapeutic products (Rebyota — rectal; Vowst — oral) are standardised alternatives to FMT.

Fidaxomicin
WHO EML/FDAA macrocyclic antibiotic — non-inferior to vancomycin for CDI cure, but associated with approximately 40% lower recurrence rate. Preferred over vancomycin for first CDI episode in patients at high risk of recurrence. Poorly absorbed — acts locally in the gut. More expensive than vancomycin but cost-effective when recurrence costs are factored in.

Bezlotoxumab (Zinplava)
FDA/EMAA human monoclonal antibody against TcdB — given as a single IV infusion alongside CDI antibiotic therapy to neutralise toxin and prevent recurrence. Reduces CDI recurrence by approximately 40% vs placebo. Recommended by FDA/EMA for patients at high risk of recurrence (≥2 prior CDI episodes, age ≥65, immunocompromised, severe CDI).

Antibiotic stewardship and CDI
WHO/ECDCThe single most important CDI prevention strategy: restricting unnecessary antibiotic use, preferring narrow-spectrum agents and shorter courses. ECDC and WHO recommend hospital antibiotic stewardship programmes as mandatory. Fluoroquinolones, clindamycin and broad-spectrum cephalosporins carry the highest CDI risk — restriction of these agents has been shown to reduce CDI rates.