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Clostridioides difficile

C. diff

Morphology: Gram-positive spore-forming anaerobic rod. Toxin A (TcdA) and toxin B (TcdB) drive disease; binary toxin in hypervirulent NAP1/027 strain.

Anaerobe

Typical drugs

  1. #1FidaxomicinIDSA 2021 first-line for initial + recurrent CDI.
  2. #2VancomycinPO 125 mg QID × 10 d (NOT IV — must be enteral). 500 mg QID PO/PR for fulminant.
  3. #3MetronidazoleIV adjunct only for fulminant ileus (oral access compromised). No longer first-line monotherapy.

Empiric therapy when resistant

Fidaxomicin or oral vancomycin remain reliably active. Bezlotoxumab (anti-toxin B mAb) adjunct for recurrence prevention. FMT (fecal microbiota transplant) for multiply recurrent disease.

Resistance mechanisms

  • Target alteration

    Reduced susceptibility to metronidazole (NAP1/027 strain)

    Example: Why metronidazole monotherapy is no longer first-line.

Resistance notes

Spore-forming — environmental persistence drives nosocomial spread. Hypervirulent NAP1/027 strain (binary toxin, fluoroquinolone-resistant) associated with worse outcomes.

Common syndromes

Pearls

Risk factors: recent antibiotics (esp. fluoroquinolones, clindamycin, broad cephalosporins), age >65, hospitalization, PPI use, IBD. Test of cure NOT recommended (PCR can stay positive for weeks). Stop the inciting antibiotic if at all possible. Don't test asymptomatic patients.

References