Chapter 123. Clostridium difficile–Associated Disease, Including Pseudomembranous Colitis (Part 4) pdf

Clostridium difficile–Associated Disease, Including Pseudomembranous Colitis Part 4 Although limited prospective randomized clinical trials showed no statistical differences among trea

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

250 mg qid x 10 d

250 mg qid x 10 da

Metronidazole

500 mg tid x 10 d

500 mg tid x 10 d

500 mg qid x 10 d

125 mg qid x 10 da

125 mg qid x 7 d

Vancomycin

125 mg qid x 5 d

400 mg bid x 10 d

Teicoplanin

100 mg bid x 10 d

Nitazoxanide 500 mg

bid x 10 da

Fusidic acid 500 mg

tid x 10 d

U qid x 10 d

a

Data from randomized trials reported in 2006