In the past, diarrhea was expected to resolve in 15% to 30% of patients with conservative therapy alone, while presumptive antibiotic treatment was reserved for patients with a high index of suspicion for pseudomembranous colitis who were particularly ill.  With the recent emergence of the epidemic strain (BI/NAP1), rapid clinical deterioration is more likely and prompt treatment should be instituted.
Metronidazole should be started presumptively in all patients with mild-to-moderate disease unless they have a contraindication to its use or are pregnant. image If the patient cannot be given metronidazole or has not responded to metronidazole within 7 days, vancomycin therapy should be initiated. 
In patients who have more severe disease, vancomycin should be started presumptively first line, because it has been shown to be more effective than metronidazole. Routine use of oral vancomycin as a first-line agent is discouraged by the CDC to avoid emergence of nosocomial vancomycin-resistant enterococci and staphylococci unless the patient has severe disease or is pregnant. Surgery may be considered for severe disease. 
Fulminant disease is associated with a 24% to 38% mortality rate. In these patients, vancomycin can be administered by retention enema or nasogastric tube, and metronidazole can be administered intravenously if necessary. The 2 agents should be administered simultaneously. Surgery may be warranted in patients who do not respond to antibiotic therapy.  Treatment relapse
Approximately 5% to 20% of patients treated with either metronidazole or vancomycin will have a recurrence after discontinuation of therapy.  Most will respond to a second course of the initial therapy. However, patients with a first recurrence have a rate of second recurrence that may be as high as 33%.  Patients with multiple recurrences are usually treated with prolonged tapering or pulsed doses of oral vancomycin, although this therapy has not been proven to be effective.