C. difficile Colitis

Toxin-mediated colitis from Clostridioides difficile overgrowth, most commonly after antibiotic exposure

Symptoms / Associated Sx

  • Watery diarrhea (≥3 loose stools/24h), lower abdominal cramping, fever

  • Leukocytosis, hypoalbuminemia in severe disease

  • Foul-smelling stool; nausea, anorexia

Denies

  • No antibiotic exposure within 8 weeks (still possible — community-acquired C. diff increasing)

  • No hospitalization, healthcare exposure, or PPI use (all risk factors)

  • Bloody diarrhea (not typical for C. diff — if present, consider concurrent colitis)

Social History (SHx)

Recent antibiotics within 8 weeks (especially clindamycin, fluoroquinolones, cephalosporins, carbapenems), hospitalization, nursing facility, PPI use, age >65, IBD, immunosuppression, prior C. diff.

Main Etiology

  • Antibiotic-mediated gut dysbiosis → C. diff spore germination + toxin A/B production

  • Nosocomial spore transmission; community-acquired (~30%); hypervirulent NAP1/BI/027 strain

Most Common DDx

  • Other infectious colitis / gastroenteritis (no recent antibiotics; stool cultures positive for Salmonella/Campylobacter/Shigella vs. C. diff PCR)

  • IBD flare (known IBD; fecal calprotectin very elevated; colonoscopy shows characteristic distribution; can coexist with C. diff — always check C. diff PCR in IBD flare)

  • Ischemic colitis (elderly; low-flow state; bloody diarrhea; CT watershed thickening; no antibiotic history needed)

  • Medication-induced diarrhea (many medications cause diarrhea without C. diff — metformin, antibiotics themselves, laxatives, magnesium; C. diff PCR negative)

  • Post-infectious IBS (watery diarrhea persisting after resolved infection; C. diff negative; stool studies negative; functional diagnosis)

  • Colorectal cancer (chronic vs. acute; colonoscopy shows mass; C. diff negative; weight loss + change in bowel habits)

DATA

  • C. diff toxin PCR (only unformed stool; do not test asymptomatic patients)

  • CBC (WBC >15k = severe; >35k = fulminant); CMP (creatinine — AKI; albumin; glucose); lactate

  • CT abdomen/pelvis (severe/fulminant — colonic wall thickening, toxic megacolon)

  • KUB (toxic megacolon — colon >6 cm)

Home Meds

  • Offending antibiotic (stop if possible); PPIs (reassess — reduce if possible)

  • Opioids (reduce motility — use cautiously); antidiarrheals (hold — toxic megacolon risk)

Plan

  • Stop offending antibiotic if possible; contact precautions + private room; soap and water (not alcohol gel)

  • Non-severe (WBC <15k AND Cr <1.5×baseline):

    • Vancomycin 125 mg PO QID × 10 days OR Fidaxomicin 200 mg PO BID × 10 days (preferred — lower recurrence)

  • Severe (WBC ≥15k OR Cr >1.5×baseline): Vancomycin 125 mg PO QID × 10 days

  • Fulminant (hypotension/shock, ileus, toxic megacolon):

    • Vancomycin 500 mg PO/NG QID + Metronidazole 500 mg IV q8h

    • If ileus: Vancomycin 500 mg enema q6h; ICU; surgery consult (colectomy if no improvement)

  • First recurrence: Fidaxomicin 200 mg BID × 10 days OR Vancomycin pulse-taper (QID × 10d → BID × 7d → daily × 7d → q2–3d × 8 weeks)

  • ≥2nd recurrence: FMT (>90% effective) — refer GI; OR Fidaxomicin extended regimen; Bezlotoxumab 10 mg/kg IV × 1 dose (adjunct, reduces recurrence ~40% in high-risk)

  • IV fluids; electrolyte replacement; avoid antidiarrheals; daily CBC, CMP; trend WBC + creatinine; fever curve

  • GI consult (severe/fulminant/recurrent); surgery consult (fulminant); PT/OT if prolonged

  • Discharge: Complete antibiotic course; minimize future antibiotic exposure; avoid PPIs if not essential; soap and water hygiene; do NOT test for cure after treatment; GI follow-up 2–4 weeks; FMT referral if ≥2 recurrences

Red Flags

  • WBC >35k or rapidly rising → fulminant → ICU + dual antibiotics + surgery consult

  • Toxic megacolon (>6 cm + systemic toxicity) → emergent colectomy

  • Hypotension + C. diff → septic shock → vancomycin + IV metronidazole + surgery

  • Ileus → vancomycin enema addition; PO may not reach colon

  • No improvement after 3–5 days → repeat CT; reconsider diagnosis; surgery consult

Senior IM Resident Pearls

  • Fidaxomicin preferred over vancomycin for initial episode (IDSA 2021) — reduces recurrence by ~40%

  • Metronidazole no longer first-line for any severity of C. diff — only IV as adjunct in fulminant disease

  • FMT >90% success for recurrent C. diff — approved donor stool via colonoscopy, enema, or capsule; refer after ≥2 recurrences

  • Bezlotoxumab — single IV dose with antibiotics; reduces recurrence ~40% in high-risk (age >65, immunocompromised, severe disease)

  • Common mistake: Alcohol-based hand sanitizer — spores are alcohol-resistant; soap and water only; bleach surface cleaning

  • Common mistake: Testing formed stool — only test unformed (≥3 loose/24h); formed stool → false positives from asymptomatic colonization

ORDERS

Labs

Admission Labs

  • CBC with diff

  • CMP

  • BMP

  • Magnesium

  • Phosphorus

  • Lactate

  • Albumin

Diagnostic Testing

C. difficile PCR/Toxin Assay

  • Only test unformed stool

  • ≥3 loose stools/24 hr

Additional Labs

  • Blood cultures ×2 (fever, severe disease, sepsis)

  • CRP

  • ESR

Trending Labs

  • CBC daily

  • BMP daily

  • CMP daily

  • Cr daily

  • WBC trend daily

  • Lactate q4–6 hr if severe/fulminant

Imaging

Usually Not Needed

Severe / Fulminant Disease

CT Abdomen/Pelvis with Contrast

Evaluate:

  • Colitis severity

  • Toxic megacolon

  • Perforation

  • Ileus

Toxic Megacolon Monitoring

KUB

Evaluate:

  • Colon diameter

Toxic megacolon:

  • Colon >6 cm

Procedures

Usually None

Recurrent Disease

FMT (Fecal Microbiota Transplant)

Indications:

  • ≥2 recurrences

  • Failure of standard therapy

Fulminant Disease

Surgical Evaluation

Possible:

  • Subtotal colectomy

  • Diverting loop ileostomy

Medications

Stop Offending Agents

Stop If Possible

  • Clindamycin

  • Fluoroquinolones

  • Cephalosporins

  • Carbapenems

  • Other unnecessary antibiotics

Reassess

  • PPIs

  • Opioids

Initial Episode

Non-Severe

Criteria:

  • WBC <15K

  • Cr <1.5 × baseline

Fidaxomicin (Preferred)

  • 200 mg PO BID x10 days

OR

Vancomycin

  • 125 mg PO QID x10 days

Severe

Criteria:

  • WBC ≥15K
    OR

  • Cr >1.5 × baseline

Vancomycin

  • 125 mg PO QID x10 days

OR

Fidaxomicin

  • 200 mg PO BID x10 days

Fulminant Disease

Criteria:

  • Hypotension

  • Shock

  • Ileus

  • Toxic megacolon

Vancomycin

  • 500 mg PO/NG QID

PLUS

Metronidazole

  • 500 mg IV q8h

If Ileus

Vancomycin Retention Enema

  • 500 mg PR q6h

Recurrence Treatment

First Recurrence

Fidaxomicin

  • 200 mg PO BID x10 days

OR

Vancomycin Pulse-Taper

Example:

  • 125 mg QID x10 days

  • Then BID x7 days

  • Then daily x7 days

  • Then every 2–3 days x8 weeks

Second or Greater Recurrence

FMT Referral

OR

Fidaxomicin Extended Regimen

High Recurrence Risk

Bezlotoxumab

  • 10 mg/kg IV x1

Consider:

  • Age >65

  • Immunocompromised

  • Severe disease

  • Recurrent disease

Supportive Care

IV Fluids

LR Preferred

  • 1–2 L bolus if dehydrated

Then:

  • Maintenance fluids

Electrolyte Replacement

  • K >4

  • Mg >2

Hold Medications

Avoid

  • Loperamide

  • Diphenoxylate-atropine

Reduce If Possible

  • PPIs

  • Opioids

Stop

  • Offending antibiotics

Consults

Gastroenterology

Indications:

  • Fulminant disease

  • Recurrent disease

  • FMT consideration

  • Toxic megacolon

General Surgery

Indications:

  • Toxic megacolon

  • Perforation

  • Fulminant disease

  • Worsening despite treatment

Infectious Disease

Indications:

  • Refractory disease

  • Multiple recurrences

  • Immunocompromised

PT/OT

  • Deconditioning

  • Prolonged hospitalization

Nursing Orders

Isolation

Contact Precautions

  • Private room

Hand Hygiene

  • Soap and water only

Environmental Cleaning

  • Bleach-based cleaning

Monitoring

  • Stool count

  • Strict I&O

  • Daily weights

  • Vital signs q4 hr

Notify Physician Immediately

  • Increasing abdominal distension

  • Hypotension

  • Fever

  • AMS

  • Decreased stool output with worsening pain (ileus)