Initial episode or first recurrence | Mild to moderate* | Metronidazole (500 mg orally, 3 times/d) | 10–14 d | Avoid metronidazole after first recurrence because of potential cumulative neurotoxicity; consider vancomycin when metronidazole is ineffective, poorly tolerated or contraindicated; fidaxomicin may be equally effective; (3) time to resolution may be shorter with vancomycin |
Severe† | Vancomycin (125 mg orally, 4 times/d) with or without metronidazole (500 mg intravenously, 3 times/d) |
Complicated‡ | Ileus, toxic megacolon, signs of shock | Vancomycin (500 mg orally or rectally, 4 times/d) with metronidazole (500 mg intravenously, 3 times/d) | 10–14 d | Consider colectomy for progressive infection in patients with severe illness |
Second or later recurrence‡ | Mild to moderate* | Vancomycin, tapering§ or pulsed regimen | Example tapering regimen: (3) 125 mg 4 times/d for 14 d 125 mg 2 times/d for 1 wk 125 mg 1 time/d for 1 wk 125 mg every 2 d for 1 wk 125 mg every 3 d for 2 wk | Consider Saccharomyces boulardii (500 mg, 2 times/d) as adjunctive therapy (3) |
Severe† | Vancomycin (500 mg orally or rectally, 4 times/d) with metronidazole (500 mg intravenously, 3 times/d) | When acute phase has resolved, consider tapering regimen as above | Avoid S. boulardii in patients who are critically ill |