Clostridioides difficile Infection Management (IDSA/SHEA 2021)

Algorithm Steps

1. ▶

   Start

   Suspected C. difficile Infection

   ≥3 unformed stools in 24h + recent antibiotic exposure or healthcare contact

   1. ●

      Action

      Diagnostic Testing

      Stool testing strategy

      • NAAT (PCR) alone: Highly sensitive, may detect colonization
      • Two-step algorithm (GDH/toxin then NAAT): Preferred by many
      • Only test unformed stool (Bristol 5-7)
      • Do NOT test for cure - avoid repeat testing <7 days
      1. ●

         Action

         Stop Inciting Antibiotics

         If clinically feasible

         • Discontinue unnecessary antibiotics ASAP
         • Avoid antiperistaltic agents
         • Contact precautions + hand hygiene with soap/water
         • Identify and isolate
         1. ◆

            Decision

            Assess Severity

            Non-severe vs Severe vs Fulminant

            • Non-severe: WBC ≤15,000, Cr <1.5
            • Severe: WBC >15,000 OR Cr >1.5 (≥1.5× baseline)
            • Fulminant: Hypotension, shock, ileus, megacolon
            1. ◆

               Decision

               Initial or Recurrent Episode?

               Recurrence = symptom return within 8 weeks of prior episode

               1. ●

                  Action

                  Initial Non-Severe CDI

                  First episode, mild-moderate

                  • PREFERRED: Fidaxomicin 200mg PO BID x10 days
                  • Alternative: Vancomycin 125mg PO QID x10 days
                  • Metronidazole 500mg PO TID x10-14 days (if above unavailable)
                  • Fidaxomicin associated with lower recurrence rates
                  1. ◆

                     Decision

                     Clinical Response

                     Assess by day 3-5

                     • Expect diarrhea improvement within 3-5 days
                     • Do NOT repeat stool testing to confirm cure
                     • Monitor for recurrence after treatment completion
                     1. ✓

                        Outcome

                        CDI Resolved

                        Symptom resolution

                        • Return to normal bowel function
                        • Monitor for recurrence (occurs in ~20-30%)
                        • Probiotics: Limited evidence for prevention
                        • Antibiotic stewardship to prevent future CDI
                     2. ⚠

                        Warning

                        Recurrence / Non-Response

                        Symptoms persist or return

                        • Confirm with repeat testing (>7 days from last test)
                        • Escalate therapy per recurrence pathway
                        • Consider FMT/microbiome restoration
                        • Rule out other causes of diarrhea
               2. ●

                  Action

                  Initial Severe CDI

                  WBC >15K or Cr >1.5

                  • PREFERRED: Fidaxomicin 200mg PO BID x10 days
                  • Alternative: Vancomycin 125mg PO QID x10 days
                  • Avoid metronidazole for severe disease
                  • Close monitoring for progression to fulminant
               3. ●

                  Action

                  First Recurrence

                  Recurrence within 8 weeks

                  • If vancomycin used initially: Fidaxomicin 200mg BID x10 days (preferred)
                  • OR Extended vancomycin taper:
                  • 125mg QID x10-14d, then BID x7d, then daily x7d, then q2-3d x2-8wks
                  • OR Vancomycin 125mg QID x10d followed by rifaximin 400mg TID x20d
               4. ●

                  Action

                  Second or Subsequent Recurrence

                  Multiple recurrences

                  • Fidaxomicin 200mg BID x10 days, OR
                  • Vancomycin taper as above, OR
                  • FMT (Fecal Microbiota Transplant) recommended after ≥2 recurrences
                  • FDA-approved microbiome therapies: Vowst (SER-109), Rebyota (fecal microbiota, live-jslm)
                  1. ●

                     Action

                     Fecal Microbiota Transplant/Restoration

                     For recurrent CDI

                     • Perform FMT after completion of vancomycin/fidaxomicin course
                     • Routes: Colonoscopy (preferred), enema, upper GI
                     • FDA-approved alternatives: Vowst (oral capsules), Rebyota (rectal)
                     • Success rate: ~80-90% for recurrent CDI
                     • Screen donors for pathogens
            2. ●

               Action

               Fulminant CDI

               Hypotension, shock, ileus, megacolon

               • Vancomycin 500mg PO/NG QID
               • PLUS Metronidazole 500mg IV q8h
               • If ileus: ADD Vancomycin 500mg in 100mL NS per rectum q6h
               • Surgical consultation IMMEDIATELY
               • Consider subtotal colectomy if refractory
               1. ⚠

                  Warning

                  Surgical Indications

                  When to consider colectomy

                  • Fulminant CDI not responding to medical therapy
                  • Toxic megacolon (colon >6cm)
                  • Colonic perforation
                  • Peritonitis, septic shock despite treatment
                  • Subtotal colectomy with end ileostomy preferred