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First trimester exposure to metronidazole is not recommended in FDA guidelines because of concern regarding ready placental transmission and case reports describing facial anomalies following exposure. Metronidazole and its active metabolites are readily detected in breast milk and in the plasma of infants.

Oral vancomycin cannot reach segments of colon that are not in continuity with the gastrointestinal tract, such as the patient with an upstream ileostomy, Hartmans pouch, or colostomy. Moreover, there are data to suggest that IV metronidazole will also enter the colon lumen following secretion across the inflamed colonic mucosa, and CDI patients who respond to treatment have a dramatic fall in the fecal concentrations of the antibiotic following initiation of therapy.

The duration of enema therapy should continue until the patient has significant improvement.