Chapter 123. Clostridium difficile–Associated Disease, Including Pseudomembranous Colitis (Part 4) Although limited prospective randomized clinical trials showed no statistical differences among treatment agents for cessation of diarrhea (the primary outcome endpoint; Table 123-2), later observational studies suggest that response rates to metronidazole may have decreased. The clinical response rate for bacitracin is 10–20% lower than that for vancomycin; therefore, bacitracin use for first-line therapy is discouraged. All drugs, particularly vancomycin, should be given orally if possible. When IV metronidazole is administered, fecal bactericidal drug concentrations are achieved during acute diarrhea, and CDAD treatment has been successful; however, in the presence of adynamic ileus, IV metronidazole treatment of PMC has failed. In previous randomized trials, diarrhea response rates to oral therapy with vancomycin or metronidazole were ≥94%, but two recent observational studies found that metronidazole response rates had declined to 74% and 78%. Although the mean time to resolution of diarrhea is 2–4 days, the response to metronidazole may be much slower. Treatment should not be deemed a failure until a drug has been given for at least 6 days. On the basis of data for shorter courses of vancomycin (Table 123-2), it is recommended that metronidazole and vancomycin be given for at least 10 days, although no controlled comparisons are available. Although metronidazole is not approved for this indication by the U.S. Food and Drug Administration (FDA), most patients with mild to moderate illness respond to 500 mg given by mouth three times a day for 10 days; extension of the treatment period may be needed for slow responders. Because of the recent increase in metronidazole failures, patients treated with this drug should be monitored carefully for progressive defervescence (if fever is present), alleviation of abdominal pain and tenderness, decreases in the number of daily bowel movements, and decreases in the white blood cell (WBC) count. Clinical deterioration, with worsening signs and symptoms, or an unexplained increase in the WBC count during treatment are indications for a switch to vancomycin (usual dose, 125 mg orally four times a day). Although the use of vancomycin is discouraged for treatment of mildly to moderately ill patients, it may be judicious to use this agent for the initial treatment of patients who appear seriously ill, particularly if they have a high WBC count (>20,000/µL); controlled clinical outcome data on vancomycin use against the epidemic strain are not available. A randomized prospective trial of the antiparasitic drug nitazoxanide showed that (although not approved by the FDA for this indication) it was at least as effective as metronidazole for the treatment of CDAD, providing a potential alternative to vancomycin and metronidazole. Table 123- 2 Expected Treatment Outcomes Based on Randomized Comparative Trials of Oral Therapy for Clostridium difficile– Associated Disease Treatment Dose and Duration Resolution of Diarrhea, % Recurrence, % Placebo or discontinuation of offending antibiotics None 21 Unknown 250 mg qid x 10 d 95 5 250 mg qid x 10 da 82 30 Metronidazole 500 mg tid x 10 d 94 17 500 mg tid x 10 d 94 17 500 mg qid x 10 d 100 15 125 mg qid x 10 da 91 19 125 mg qid x 7 d 86 33 Vancomycin 125 mg qid x 5 d 75 Unknown 400 mg bid x 10 d 96 7 Teicoplanin 100 mg bid x 10 d 96 8 Nitazoxanide 500 mg bid x 10 d a 89 22 Fusidic acid 500 mg tid x 10 d 93 28 Bacitracin 25,000 U qid x 10 d 80 42 a Data from randomized trials reported in 2006. . Chapter 123. Clostridium difficile–Associated Disease, Including Pseudomembranous Colitis (Part 4) Although limited prospective randomized clinical. alternative to vancomycin and metronidazole. Table 123- 2 Expected Treatment Outcomes Based on Randomized Comparative Trials of Oral Therapy for Clostridium difficile– Associated Disease Treatment. been given for at least 6 days. On the basis of data for shorter courses of vancomycin (Table 123- 2), it is recommended that metronidazole and vancomycin be given for at least 10 days, although