| Severity | Criteria |
|---|---|
| Non-severe | WBC โค 15,000 AND Cr < 1.5 mg/dL |
| Severe | WBC > 15,000 OR Cr โฅ 1.5 |
| Fulminant | Hypotension, shock, ileus, or megacolon |
| Severity | First Episode | First Recurrence | Second+ Recurrence |
|---|---|---|---|
| Non-severe | Fidaxomicin 200 mg PO BID ร 10 days PREFERRED OR vancomycin 125 mg PO QID ร 10 days | Fidaxomicin 200 mg PO BID ร 10 days (preferred) or vancomycin pulse-taper | Vancomycin pulse-taper, fidaxomicin, or fecal microbiota transplant (FMT) |
| Severe | Vancomycin (Vancocin) 125 mg PO QID ร 10 days OR fidaxomicin 200 mg PO BID ร 10 days | Same as first episode + consider FMT | FMT strongly recommended |
| Fulminant | Vancomycin 500 mg PO/NG QID + metronidazole 500 mg IV q8h. If ileus: add vancomycin retention enemas 500 mg in 100 mL NS q6h. Surgical consult โ subtotal colectomy if toxic megacolon, perforation, or no improvement. | Same approach. Early surgical involvement critical. | |
| Test | Rationale | Key Values / Notes |
|---|---|---|
| Stool C. diff testing | Confirm diagnosis. Use institutional algorithm -do NOT order both PCR and toxin independently. | NAAT/PCR = highly sensitive (detects carriers). Toxin EIA = specific for active disease. Best approach: GDH screen โ toxin EIA, or NAAT + toxin EIA. PCRโบ/toxinโป = possible carrier -use clinical judgment. |
| CBC with differential | WBC stratifies severity and identifies fulminant disease. | WBC > 15K = severe. WBC > 30K = fulminant (high mortality). Bandemia and left shift common. |
| BMP (Cr) | Creatinine defines severity. Monitor renal function during illness. | Cr โฅ 1.5 mg/dL = severe (IDSA/SHEA criteria). Also check Kโบ (diarrheal losses) and bicarb. |
| Lactate | Elevated lactate = fulminant disease or sepsis. | Lactate > 5 mmol/L = fulminant CDI. Indicates tissue hypoperfusion -consider surgical consult. |
| CT abdomen/pelvis | If concern for fulminant disease, toxic megacolon, or perforation. | Colonic wall thickening, pericolonic stranding, "accordion sign." Colon > 6 cm = megacolon โ urgent surgical consult. |
| Abdominal X-ray | Rapid screen for megacolon if CT not immediately available. | Dilated colon, thumbprinting, pneumatosis. Less sensitive than CT. |
| Drug | Dose | Route | Indication | Key Notes |
|---|---|---|---|---|
| Fidaxomicin (Dificid) FIRST-LINE | 200 mg BID ร 10 days | PO | First-line for initial and recurrent episodes (non-severe and severe) | Narrow-spectrum -preserves gut flora โ lower recurrence (~13% vs ~27% for vancomycin) IDSA/SHEA, 2021. Main limitation: cost (~$3,000). |
| Vancomycin PO | 125 mg QID ร 10 days | PO | Alternative first-line. Standard-dose for non-severe and severe. | 500 mg QID for fulminant disease. Not absorbed systemically -acts locally in gut. IV vancomycin does NOT treat C. diff (does not reach colon). |
| Vancomycin pulse-taper | 125 mg QID ร 14d โ BID ร 7d โ daily ร 7d โ q2d ร 7d โ q3d ร 14d | PO | First and subsequent recurrences | Gradual taper allows spore germination between doses, then kills vegetative forms. Effective for breaking recurrence cycle. |
| Metronidazole (Flagyl) | 500 mg IV q8h | IV | Fulminant CDI adjunct ONLY (with PO/PR vancomycin) | NO longer recommended as monotherapy for any severity. IV metronidazole reaches colon via biliary excretion -useful when ileus prevents oral drug delivery. |
| Vancomycin enemas | 500 mg in 100 mL NS q6h | PR | Fulminant CDI with ileus (oral medications cannot reach colon) | Given in addition to PO/NG vancomycin and IV metronidazole. Retain for 60 minutes if possible. |
| Bezlotoxumab (Zinplava) | 10 mg/kg IV ร 1 dose | IV | Recurrence prevention in high-risk patients (during active treatment course) | Anti-toxin B monoclonal antibody. Reduces recurrence by ~40% MODIFY I/II, 2017. Consider if: age โฅ 65, immunocompromised, severe CDI, or prior recurrence. |
| Fecal microbiota transplant (FMT) | Per protocol (colonoscopic, capsule, or enema) | Various | After โฅ 2 recurrences despite appropriate antibiotic therapy | ~85-90% cure rate for recurrent CDI. FDA-approved products now available (RBX2660/Rebyota, SER-109/Vowst). Restores normal gut microbiome. |
Presentation: 68F admitted for UTI on ceftriaxone ร 3 days, now with 5 episodes of watery, non-bloody diarrhea over 24 hours. Afebrile, hemodynamically stable. Mild LLQ tenderness without peritoneal signs.
Labs: WBC 12,000 (no bandemia), Cr 0.9 mg/dL (baseline), lactate 1.1 mmol/L. Stool GDH positive, toxin EIA positive.
Classification: Non-severe CDI (WBC โค 15K, Cr < 1.5).
Management:
Presentation: 72M with recent hospitalization for pneumonia (completed levofloxacin course), re-admitted with profuse watery diarrhea ร 3 days, now with abdominal distension, absent bowel sounds, fever 39.2ยฐC, HR 118, BP 82/50 on 2L NS bolus.
Labs: WBC 28,000 with 15% bands, Cr 2.8 mg/dL (baseline 1.0), lactate 4.2 mmol/L, albumin 1.9. CT abdomen: diffuse colonic wall thickening with pericolonic stranding, transverse colon dilated to 7.5 cm, toxic megacolon.
Classification: Fulminant CDI (hypotension, ileus, megacolon, WBC > 15K, elevated lactate).
Management:
Presentation: 55F with third episode of C. diff in 6 months. First episode treated with vancomycin 125 mg PO QID ร 10 days, recurred 3 weeks after completion. Second episode treated with vancomycin pulse-taper ร 6 weeks, recurred again 2 weeks after stopping. Now with 6 watery stools/day, cramping, WBC 11,000, Cr 0.8. Stool toxin positive.
Classification: Non-severe, second recurrence (third episode overall). Standard antibiotic therapy has failed.
Management Options:
| Parameter | Frequency | Target / Action |
|---|---|---|
| Stool frequency | Daily (nursing stool count) | Expect improvement in 3-5 days. Stool frequency should decrease. Diarrhea may persist for days even with effective treatment -judge by trend, not single day. |
| WBC | Daily if severe or fulminant; q2-3 days if non-severe | Trending down = improving. Rising WBC (especially > 30K) = worsening โ reassess severity, consider surgical consult. Leukemoid reaction (> 40K) is a poor prognostic sign. |
| Creatinine | Daily if severe/fulminant; at baseline and mid-course if non-severe | Rising Cr = worsening (may need to escalate therapy). AKI from volume depletion -ensure adequate hydration. |
| Lactate | q6-12h if severe or fulminant | Lactate > 5 = fulminant disease. Rising lactate = tissue hypoperfusion โ ICU, surgical consult. |
| Abdominal exam | At least daily; more frequently if severe/fulminant | Increasing distension, tenderness, guarding, rigidity โ CT imaging, surgical consult. Absent bowel sounds + distension = ileus (add rectal vancomycin). |
| Volume status | Each assessment | Aggressive IV fluid resuscitation for dehydration from diarrhea. Monitor UOP, orthostatics, mucous membranes. |