C. difficile infection
CDI = new ≥3 watery stools/day + positive toxin/NAAT interpreted in context (colonization vs disease).
Colonization is not colitis
CDI is new-onset symptoms — usually ≥3 watery stools in 24 hours — plus evidence of a toxin-producing Clostridioides difficile or pseudomembranous colitis (/SHEA ; ; ). Spores, fecal–oral; disease needs both acquisition and a wrecked microbiome.
- Risks: antibiotics in 3 months (BL/BLI combinations, 3rd/4th-gen cephalosporins, FQ, carbapenems, clindamycin), age ≥65, recent hospitalization / long LOS, IBD, chemo, GI surgery, tube feeds, PPI/H2RA, solid-organ transplant.
- Community-acquired CDI is ~1/3 of new cases: no hospitalization in 12 weeks. Food, pets, household, infants, clinic visits.
- Toxin A is enterotoxic, toxin B cytotoxic. Watery diarrhea ± mucus/occult blood; ileus, fever, pain, leukocytosis when severe.
PCR
Toxin B gene NAAT
Very sensitive. Positive without disease if the strain carries the gene and is not expressing it — colonization.
GDH
Glutamate dehydrogenase
Made by all C. difficile. Sensitive; cannot separate toxigenic from non-toxigenic.
Toxin
Toxin A/B EIA
Detects actual toxin. Specific, less sensitive. PCR+/toxin− is the stewardship fight.
Do not retest within 7 days without a real clinical change. Do not send test of cure — PCR can stay positive for 6 weeks.
Nonfulminant vs fulminant
IDSA 2021 focused update. Duration 10 days for non-fulminant; if they must stay on other antibiotics, some extend CDI therapy 7 days after those stop.
| Category | Criteria | Treatment |
|---|---|---|
| Non-severe | WBC <15 and creatinine <1.5 | Fidaxomicin 200 mg PO BID × 10 days (preferred, fewer recurrences) or vancomycin 125 mg PO q6h × 10 days. Metro 500 mg PO q8h × 10–14 days only if the others are unavailable. |
| Severe | WBC >15 or creatinine >1.5 | Same oral agents. Stop antimotility drugs, nonessential antibiotics, and cholestyramine (it binds vancomycin). |
| Fulminant | Hypotension / , ileus, or megacolon | Vancomycin 500 mg PO q6h AND metronidazole 500 mg IV q8h. Ileus: add vancomycin 500 mg in 100 mL NS as a retention enema q6h. Surgical consult. Consider FMT if ileus, nonresponse, or recurrent disease. |
First recurrence
- Fidaxomicin 200 mg BID × 10 days, or 200 mg BID × 5 then every other day × 20.
- If the first episode was metronidazole: vancomycin 125 mg × 10 days.
- Pulse-tapered vancomycin 125 mg over 6–8 weeks.
- Consider bezlotoxumab 10 mg/kg IV × 1 with fidaxomicin or vancomycin if another episode in 6 months.
Second recurrence
- Same fidaxomicin strategies, pulse-tapered vancomycin, or vancomycin 125 mg q6h × 10 days then rifaximin 400 mg TID × 20, plus bezlotoxumab.
- : evaluate for fecal microbiota transplant after the second recurrence ().
- Refractory (never resolved on therapy) is rare — think another diagnosis, not a third drug.
- Infection control: contact precautions. Soap and water after contact — alcohol gel does not kill spores.
- Secondary prophylaxis: vancomycin 125 mg PO daily during systemic antibiotics plus 7 days after may cut recurrence. Practice varies (). Primary prophylaxis in very high-risk patients is discussed, not automatic.
- CT A/P if fulminant or to look for megacolon / perforation. Flex sig only when you need a look or a biopsy for an alternate diagnosis.