Clostridioides difficile infection: recognition, treatment, and prevention

Clostridioides difficile infection (CDI) is the leading cause of hospital-acquired diarrhoea and a significant cause of community-acquired diarrhoea in Australia. It occurs when antibiotic disruption of the normal gut microbiome allows C. difficile — an anaerobic spore-forming Gram-positive bacillus — to overgrow and produce toxins A and B, causing colonic inflammation ranging from mild diarrhoea to life-threatening fulminant colitis.

The Australian Commission on Safety and Quality in Health Care (ACSQHC) tracks hospital CDI rates as a quality and safety indicator. The incidence in Australian hospitals is approximately 3–5 cases per 10,000 patient-days. Importantly, community-acquired CDI — in people without recent hospitalisation — now represents approximately 30–40% of cases, making GP recognition increasingly important.

This article covers clinical recognition, diagnostic testing, treatment by severity, recurrence management, and prevention. The GP’s roles are to recognise CDI, initiate appropriate treatment, refer severe cases, and counsel patients on recurrence risk.

A. Core clinical — the AU general-practice framework

Risk factors

The most common precipitating antibiotics are the “4 Cs”: clindamycin, cephalosporins (especially third-generation), co-amoxiclav, and ciprofloxacin/fluoroquinolones. Broad-spectrum penicillins (piperacillin-tazobactam) also carry significant risk. Any antibiotic can precipitate CDI in a susceptible host.

Additional risk factors:

• Recent healthcare exposure (hospital, residential aged care, renal dialysis) within 12 weeks
• Age ≥65 years
• Prior CDI (recurrence risk ~25% after first episode)
• Inflammatory bowel disease
• Immunosuppression (chemotherapy, corticosteroids, transplant, haematological malignancy)
• Proton pump inhibitor (PPI) use — modest independent risk
• GI surgery or instrumentation
• Malnutrition

Clinical presentation

Classic presentation: diarrhoea (≥3 unformed stools in 24 hours), watery or loose, foul-smelling, with abdominal cramping, occurring within 8 weeks of antibiotic exposure or healthcare contact.

Severity markers (IDSA 2021 classification):

Severity	Definition
Non-severe	WBC ≤15,000/μL and creatinine <133 μmol/L
Severe	WBC >15,000/μL or creatinine >133 μmol/L (>1.5× baseline)
Fulminant	Hypotension or shock, ileus, or toxic megacolon

Blood tests useful in severity assessment: FBC (WBC), urea and electrolytes, creatinine, CRP, albumin (hypoalbuminaemia = severity marker), and lactate in fulminant disease. Plain abdominal X-ray or CT abdomen when severe — colonic dilation >6 cm indicates toxic megacolon.

Diagnostic testing

Do not test asymptomatic patients. The colonisation rate with non-toxigenic C. difficile is ~5% in healthy adults and over 25% in hospitalised patients; testing asymptomatic carriers generates false positives and inappropriate treatment.

Two-step testing (preferred in Australian laboratories):

1. Glutamate dehydrogenase (GDH) antigen — highly sensitive; screens for any C. difficile presence
2. Toxin A/B EIA — specific; confirms toxin-producing strain
3. PCR for toxin genes — used as a tiebreaker when GDH positive and toxin EIA negative

A PCR-only test is sensitive but cannot distinguish active toxin production from passive carriage — over-diagnosis risk if used without the two-step algorithm.

Differential diagnosis

Condition	Distinguishing features
Antibiotic-associated diarrhoea (non-CDI)	Mild; toxin negative; resolves on stopping antibiotic
Inflammatory bowel disease flare	Chronic history; biopsies; CDI can complicate IBD — test first
Infectious colitis (Salmonella, Campylobacter, Shigella, EHEC)	Stool culture + PCR; epidemiological exposure; usually self-limiting
Microscopic colitis	Chronic watery diarrhoea; histology required; no toxin
Ischaemic colitis	Older patient; vascular risk factors; CT findings
Drug-induced colitis (immune checkpoint inhibitor)	Drug history; oncology context; biopsy

B. Evidence appraisal — treatment strategy

Fidaxomicin versus vancomycin

The Cornely Lancet Infect Dis 2012 trial compared fidaxomicin with vancomycin in a randomised trial and demonstrated equivalent clinical cure rates but a significantly lower recurrence rate with fidaxomicin (~15% vs ~25%). This recurrence reduction was particularly pronounced in non-NAP1 strains (the strain type more common in Australia). IDSA 2021 and ESCMID 2021 guidelines list fidaxomicin as the preferred first-line agent. Vancomycin remains an acceptable PBS-listed alternative widely used in Australian practice due to cost and availability.

Metronidazole demotion

Multiple trials demonstrate metronidazole has inferior clinical cure and higher recurrence rates compared to vancomycin and fidaxomicin. eTG Antibiotic reflects the 2021 guidance demotion: metronidazole is now reserved for resource-limited settings where vancomycin and fidaxomicin are genuinely unavailable.

Bezlotoxumab

The MODIFY-I and MODIFY-II trials (Wilcox NEJM 2017) — a single IV infusion of bezlotoxumab (anti-toxin B monoclonal antibody, 10 mg/kg) — reduced CDI recurrence by approximately 40% compared to placebo in high-risk patients. It is PBS Section 100 in Australia since 2018 for selected indications: patients with at least one episode of CDI within the past 6 months, age ≥65, severe or fulminant index episode, or immunocompromised status.

Faecal microbiota transplantation (FMT)

The landmark van Nood NEJM 2013 trial demonstrated FMT superiority to vancomycin for recurrent CDI (resolution ~81% vs ~31%). Multiple subsequent RCTs and meta-analyses confirm resolution rates of approximately 85–90% for recurrent CDI. FMT is regulated as a therapeutic good by the TGA in Australia since 2020; all FMT programs operate within this framework with screened donor stool banks.

C. Treatment by severity

Stop the offending antibiotic — and review the PPI

The first action is to stop or de-escalate the precipitating antibiotic if clinically safe to do so. Also review whether the PPI is strictly necessary — deprescribing where not indicated modestly reduces CDI risk.

Hydration and electrolyte replacement are core to all cases. Avoid loperamide — theoretical risk of toxin retention and precipitation of toxic megacolon.

Initial episode — non-severe and severe

Preferred: fidaxomicin 200 mg orally twice daily for 10 days (PBS Authority required in AU).

Alternative: vancomycin 125 mg orally four times daily for 10 days (PBS-listed).

Metronidazole is not used as first-line for either non-severe or severe initial episodes.

Initial episode — fulminant

• Vancomycin 500 mg orally four times daily (or via nasogastric tube) + IV metronidazole 500 mg every 8 hours (synergistic when ileus limits oral vancomycin absorption)
• Rectal vancomycin 500 mg in 100 mL saline per rectum every 6 hours if significant ileus
• Urgent surgical consultation — subtotal colectomy may be life-saving
• ICU admission and sepsis bundle management

First recurrence

• Fidaxomicin 200 mg twice daily for 10 days (preferred), or fidaxomicin extended pulsed/tapered regimen
• Or: pulsed/tapered vancomycin — 125 mg four times daily for 10–14 days, then twice daily for 7 days, then once daily for 7 days, then every 2 days for 8 days, then every 3 days for 15 days

Consider bezlotoxumab at this point if the patient has high-risk features for further recurrence (age ≥65, prior CDI episode, immunosuppression, or severe initial episode) — single IV infusion, PBS Section 100.

Multiple recurrences (≥2 episodes)

Faecal microbiota transplantation (FMT) is the treatment of choice — approximately 85–90% success rate. Refer to a gastroenterologist or infectious diseases specialist at a major FMT centre: Westmead, Royal Prince Alfred (Sydney), Royal Melbourne, Royal Brisbane and Women’s Hospital, Sir Charles Gairdner (Perth), or Royal Adelaide Hospital. Encapsulated oral FMT is an emerging delivery route gaining traction in Australian centres.

D. Australian operations

Antibiotic stewardship — prevention is everything

The single most effective CDI prevention strategy is antimicrobial stewardship: using antibiotics only when indicated, choosing the narrowest-spectrum agent, and using the shortest course consistent with clinical goals. The ACSQHC mandates antimicrobial stewardship programmes in all Australian hospitals. GP prescribing patterns — particularly fluoroquinolone and cephalosporin use — directly influence community CDI rates. The NPS MedicineWise Antibiotic Awareness resources support rational prescribing.

Infection prevention

• Handwashing with soap and water — not alcohol gel — when caring for a patient with CDI; soap mechanically removes spores where alcohol fails
• Environmental cleaning with chlorine-based (bleach) solutions — C. difficile spores survive on surfaces for months; standard quaternary ammonium disinfectants are inadequate
• Contact precautions in hospital — gown, gloves, private room with dedicated toilet

MBS and PBS items (verify before billing)

• Standard GP consultations: items 23 / 36 / 44
• Stool testing: Community pathology rebatable via Medicare; request stool toxin EIA/GDH/PCR
• Vancomycin oral: PBS Authority item for CDI; standard 125 mg four times daily for 10 days
• Fidaxomicin (Dificid): PBS Authority item for CDI (verify current restriction)
• Metronidazole oral: PBS-listed general (not Authority); appropriate for resource-limited use only
• Bezlotoxumab (Zinplava): PBS Section 100; specialist initiation; single IV infusion; specific high-risk recurrence criteria
• Colonoscopy: specialist-initiated; MBS items 32072 / 32084 series

Notification and surveillance

CDI is not nationally notifiable to public health. The ACSQHC tracks hospital CDI rates as a quality indicator. Outbreak clusters in healthcare settings should be notified to the facility infection-prevention team and, for significant outbreaks, to the local public health unit.

E. Special populations

Older adults (≥65 years). The highest-risk group — older age is both a risk factor for CDI and for severe disease and mortality. WBC >15,000 in an older adult requires hospital admission for monitoring. Fidaxomicin is particularly preferred to reduce recurrence risk in this group. Review all medications: PPIs, antibiotics, and laxatives may all need rationalisation.

Patients with inflammatory bowel disease (IBD). CDI can complicate both ulcerative colitis and Crohn’s disease, precipitating a severe flare. Always test for CDI before attributing new diarrhoea to an IBD flare and before escalating immunosuppression. CDI in IBD is managed with fidaxomicin or vancomycin per standard protocol; the IBD treatment may need adjustment; early gastroenterology involvement is recommended.

Immunocompromised patients. Chemotherapy recipients, transplant patients, and those on high-dose corticosteroids are at risk of severe, prolonged, or treatment-refractory CDI. Bezlotoxumab after the first episode is worth considering earlier in this group, given the high recurrence risk. FMT in severely immunocompromised patients requires specialist-centre assessment given theoretical infection risks from donor stool.

Residential aged care. The residential aged care setting combines high risk (older, polypharmacy, frequent antibiotic exposure, shared facilities) with limited resources for isolation. Early liaison with the facility and, if outbreak, the Public Health Unit is important. Handwashing with soap and water protocols in residents and staff are essential.

Pregnancy. CDI in pregnancy is uncommon but serious. Oral vancomycin or fidaxomicin are the agents of choice — both act locally in the gut with negligible systemic absorption. Avoid IV metronidazole in first trimester where possible. Early gastroenterology and obstetric involvement.

When to escalate

Admit to hospital or call immediately for:

• Severe CDI (WBC >15,000 or creatinine >1.5× baseline) — IV access, monitoring, and consideration of IV metronidazole + oral vancomycin
• Fulminant CDI — hypotension, ileus, or radiological toxic megacolon — surgical consultation urgently
• Any sign of peritonism (rebound tenderness, guarding, rigidity) — perforation excluded by CT
• Sepsis features in a patient with diarrhoea

Refer to gastroenterology / infectious diseases:

• First recurrence — for fidaxomicin extended regimen, bezlotoxumab assessment, and FMT planning
• Multiple recurrences (≥2 episodes) — FMT
• CDI in IBD — complex management, avoid immunosuppression escalation before ruling out CDI
• Immunocompromised patients with recurrent CDI — specialist FMT assessment

What this article is and is not

This is general health information drawn from current Australian and international guidelines — eTG Antibiotic, AMH, IDSA 2021 CDI guideline, ESCMID 2021 CDI guideline, ACSQHC, and GESA FMT standards. It is not personal medical advice and does not replace assessment by your GP or treating clinician.

If you have diarrhoea after antibiotics, contact your GP — do not self-treat with further antibiotics or stop prescribed treatment without medical advice. For urgent symptoms (high fever, severe abdominal pain, blood in stool, significant dehydration) present to an emergency department. For general consumer information: HealthDirect.

---

Sources cited

1. Johnson S et al. — IDSA CDI Clinical Practice Guidelines 2021. Clin Infect Dis 2021;73:e1029
2. van Prehn J et al. — ESCMID CDI Guideline 2021. Clin Microbiol Infect 2021;27 Suppl 2:S1–S21
3. Therapeutic Guidelines (eTG) — Antibiotic
4. Australian Medicines Handbook (AMH)
5. Cornely OA et al. — Fidaxomicin vs vancomycin. Lancet Infect Dis 2012;12:281
6. Wilcox MH et al. — MODIFY-I and MODIFY-II: bezlotoxumab for CDI. NEJM 2017;376:305
7. van Nood E et al. — FMT for recurrent CDI. NEJM 2013;368:407
8. ACSQHC — Clostridioides difficile infection in Australian hospitals
9. GESA — FMT standards
10. NPS MedicineWise — Antimicrobial stewardship
11. HealthDirect — Diarrhoea