Past, present, and future therapies for Clostridium difficile-associated disease.

Objective: To describe and examine the past, present, and potential future treatment options for Clostridium difficile-associated disease (CDAD).

Data Sources: A PubMed search, restricted to English-language articles concerning CDAD, was conducted (1965-October 2006) using the key words Clostridium difficile, diarrhea, vancomycin, metronidazole, immunoglobulin, and recurrence. Additional references were located through review of the bibliographies of cited articles and by visiting www.clinicaltrials.gov.

Study Selection And Data Extraction: Articles related to the clinical manifestations, diagnosis, and treatment of CDAD, as well as articles addressing current issues related to CDAD, were included.

Data Synthesis: There have been many investigations into CDAD because of the recent increased incidence and morbidity and mortality of the disease. Various studies examining the changing epidemiology and pathogenicity of C. difficile, as well as new therapies for CDAD with agents such as tolevamer and nitazoxanide, are ongoing. In addition, researchers are investigating probiotics and vaccines to evaluate their effectiveness in preventing CDAD and/or preventing recurrences of CDAD. Studies assessing therapies for refractory CDAD are lacking, although case reports have been published citing treatment strategies using vancomycin enemas, intravenous metronidazole, colestipol and cholestyramine, fecal enemas, bowel irrigation, and immunoglobulin. Furthermore, judicious use of antimicrobials, contact precautions, and adequate environmental cleaning are being evaluated in healthcare institutions as methods for controlling and preventing the spread of C. difficile.

Conclusions: Oral metronidazole is the drug of choice for an initial CDAD episode. Oral vancomycin is an option for patients who cannot take or fail treatment with oral metronidazole. Clinical trials are necessary to define the therapy for initial CDAD that is most appropriate and produces lower recurrence rates compared with oral metronidazole or vancomycin treatment. Moreover, appropriate treatment for patients with multiple recurrences of or refractory CDAD needs to be determined. More studies are also needed assessing prevention of recurrences of CDAD.