Summary

IDSA/SHEA 2021 focused update on management of Clostridioides difficile infection (CDI) in adults, addressing the use of fidaxomicin and bezlotoxumab. Fidaxomicin is now preferred over vancomycin for both initial and recurrent CDI episodes (conditional recommendations), reflecting lower recurrence rates. Bezlotoxumab is suggested as an adjunct to standard-of-care antibiotics for patients with recurrent CDI within the past 6 months, especially those with additional risk factors for recurrence.

Key Recommendations

For an initial CDI episode, prefer fidaxomicin over a standard course of oral vancomycin; vancomycin remains an acceptable alternative.
For recurrent CDI, prefer fidaxomicin (standard or extended-pulsed regimen) over a standard vancomycin course.
Acceptable alternatives for a first CDI recurrence include tapered/pulsed vancomycin or a standard vancomycin course.
For multiple CDI recurrences, options include fidaxomicin, tapered/pulsed vancomycin, vancomycin followed by rifaximin, or fecal microbiota transplantation (FMT).
Reserve FMT until appropriate antibiotic therapy has failed for at least 2 recurrences (i.e., ≥3 CDI episodes).
Add bezlotoxumab to SOC antibiotics for patients with a recurrent CDI episode within the past 6 months, particularly with additional risk factors (age ≥65, immunocompromise, severe CDI).
Use bezlotoxumab cautiously in patients with a history of congestive heart failure—reserve for cases where benefit outweighs risk (FDA warning).
For fulminant CDI (hypotension/shock, ileus, or megacolon), use high-dose oral vancomycin plus IV metronidazole; add rectal vancomycin if ileus is present. Fidaxomicin is not recommended for fulminant CDI.
Metronidazole is only an alternative for nonsevere CDI when fidaxomicin and vancomycin are unavailable.
Data on combining bezlotoxumab with fidaxomicin are limited; most trial patients received vancomycin or metronidazole as SOC.

Thresholds & Doses

Fidaxomicin standard regimen: 200 mg PO twice daily for 10 days.
Fidaxomicin extended-pulsed regimen: 200 mg PO twice daily for 5 days, then once every other day on days 7–25.
Vancomycin standard regimen: 125 mg PO four times daily for 10 days.
Vancomycin tapered/pulsed example: 125 mg QID × 10–14 days, then BID × 7 days, then daily × 7 days, then every 2–3 days for 2–8 weeks.
Vancomycin + rifaximin chaser: vancomycin 125 mg PO QID × 10 days, followed by rifaximin 400 mg PO TID × 20 days.
Fulminant CDI: vancomycin 500 mg PO/NG QID + IV metronidazole 500 mg every 8 hours; add rectal vancomycin if ileus.
Metronidazole (nonsevere CDI, if fidaxomicin/vancomycin unavailable): 500 mg PO TID for 10–14 days.
Nonsevere CDI defined as WBC ≤15,000 cells/µL AND serum creatinine <1.5 mg/dL.
Bezlotoxumab: 10 mg/kg IV as a single 60-minute infusion during SOC antibiotic course.
Bezlotoxumab eligibility window: recurrent CDI within the last 6 months.
Recurrence risk factors favoring bezlotoxumab: age ≥65 years, immunocompromised host, severe CDI on presentation, prior CDI in last 6 months.

Citations

Recommendation I (Initial CDI) — fidaxomicin preferred over vancomycin (conditional, moderate certainty).
Recommendation II (Recurrent CDI) — fidaxomicin (standard or extended-pulsed) preferred over vancomycin (conditional, low certainty).
Recommendation III (Bezlotoxumab) — adjunct to SOC for recurrent CDI within last 6 months (conditional, very low certainty).
Table: Recommendations for the Treatment of CDI in Adults — drug doses, regimens, and fulminant CDI management.
Table 2 (PICO 1) — fidaxomicin vs vancomycin in initial CDI, sustained response RR 1.16 (1.09–1.24).
Table 3 (PICO 2) — fidaxomicin vs vancomycin in recurrent CDI, sustained response RR 1.27 (1.05–1.54) at 30 days.
Table 4 (PICO 3) — bezlotoxumab + SOC vs SOC, CDI recurrence RR 0.62 (0.51–0.75) at 12 weeks.
Bezlotoxumab Implementation Considerations / FDA warning — caution in CHF (RR for HF 2.64 [1.00–7.03]).