Infectious Disease · IDSA

Clostridioides difficile infection

IDSA

Source:IDSA/SHEA 2021 Focused Update on Management of Clostridioides difficile Infection in AdultsACG 2021 Clinical Guidelines

Verified Apr 2026

Ask House about this guideline

Red Flags

Fulminant CDI — hypotension/shock, ileus, megacolon — surgical consult; vancomycin PO 500 mg QID + IV metronidazole; consider colectomy^[1]
Severe CDI: WBC ≥15 ×10⁹/L OR creatinine ≥1.5× baseline — admit; oral fidaxomicin or vancomycin^[1]
Multiple recurrences (≥3 episodes) — faecal microbiota transplant or bezlotoxumab plus standard antibiotic; recurrence cycles can be life-altering^[1]
CDI in inflammatory bowel disease flare — high mortality; treat both; do NOT use anti-motility agents (loperamide)^[1]

First-line treatment

Interventions

Faecal microbiota transplant (FMT)^[1]
For ≥3 recurrent episodes despite appropriate antibiotic therapy; via colonoscopy, NG tube, or oral capsules. ~85% efficacy
Discontinue inciting antibiotic where possible^[1]
Stop the offending antimicrobial (especially fluoroquinolones, clindamycin, broad-spectrum cephalosporins, carbapenems) where clinically feasible

First-line drug therapy

Drug	Class	Adult	Paediatric	Notes
Fidaxomicin^[1]	Macrocyclic antibiotic (preferred)	200 mg PO BD × 10 days OR extended-pulsed regimen (200 mg BD × 5 days then alternate days × 20 days)	Per package weight-based dosing for ≥6 months	Preferred over vancomycin for initial episode and first recurrence per 2021 update; lower recurrence rate
Vancomycin (oral)^[1]	Glycopeptide (oral, non-absorbed)	125 mg PO QID × 10 days for non-fulminant; 500 mg PO QID for fulminant (with rectal vancomycin if ileus)	10 mg/kg PO QID (max 125 mg)	Alternative first-line; first choice for fulminant disease and where fidaxomicin unavailable
Metronidazole (IV) for fulminant^[1]	Nitroimidazole (parenteral adjunct)	500 mg IV q8h plus oral/rectal vancomycin	—	ADJUNCT in fulminant CDI; oral metronidazole NO LONGER recommended for non-severe CDI per 2021 update
Bezlotoxumab^[1]	Monoclonal antibody against C. difficile toxin B	10 mg/kg IV single dose during standard antibiotic course	—	Reduces recurrence in high-risk patients (age ≥65, immunocompromised, severe CDI, prior recurrence). Avoid in NYHA III–IV CHF

Fidaxomicin^[1]

Macrocyclic antibiotic (preferred)

Adult: 200 mg PO BD × 10 days OR extended-pulsed regimen (200 mg BD × 5 days then alternate days × 20 days)
Paediatric: Per package weight-based dosing for ≥6 months

Preferred over vancomycin for initial episode and first recurrence per 2021 update; lower recurrence rate

Vancomycin (oral)^[1]

Glycopeptide (oral, non-absorbed)

Adult: 125 mg PO QID × 10 days for non-fulminant; 500 mg PO QID for fulminant (with rectal vancomycin if ileus)
Paediatric: 10 mg/kg PO QID (max 125 mg)

Alternative first-line; first choice for fulminant disease and where fidaxomicin unavailable

Metronidazole (IV) for fulminant^[1]

Nitroimidazole (parenteral adjunct)

Adult: 500 mg IV q8h plus oral/rectal vancomycin
Paediatric: —

ADJUNCT in fulminant CDI; oral metronidazole NO LONGER recommended for non-severe CDI per 2021 update

Bezlotoxumab^[1]

Monoclonal antibody against C. difficile toxin B

Adult: 10 mg/kg IV single dose during standard antibiotic course
Paediatric: —

Reduces recurrence in high-risk patients (age ≥65, immunocompromised, severe CDI, prior recurrence). Avoid in NYHA III–IV CHF

Safety-net

Wash hands with SOAP and water — alcohol gel does NOT kill C. difficile spores^[1]
Diarrhoea, fever, abdominal pain after recent antibiotic — same-day medical review with stool sample^[1]
Avoid loperamide and other anti-motility agents — risk of toxic megacolon^[1]

Referral criteria

Fulminant CDI with shock, ileus, or megacolonSurgery and gastroenterology same-day^[1]
Recurrent CDI (≥2 recurrences)Gastroenterology and infectious diseases for FMT or bezlotoxumab^[1]
CDI in IBD flare or pregnancyJoint gastroenterology and infectious diseases^[1]

Clinical summary

Diagnosis and management of CDI in adults — fidaxomicin or vancomycin first-line; bezlotoxumab and FMT for recurrence.

References

1.IDSA/SHEA 2021 Focused Update on Management of Clostridioides difficile Infection in Adults; ACG 2021 Clinical Guidelines (2021)

Drug

Class

Adult

Paediatric

Notes

Fidaxomicin^[1]

Macrocyclic antibiotic (preferred)

200 mg PO BD × 10 days OR extended-pulsed regimen (200 mg BD × 5 days then alternate days × 20 days)

Per package weight-based dosing for ≥6 months