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INFECTIOUS DISEASES

Emerging Therapies in the Treatment of Clostridium difficile-Associated Disease

Assistant Clinical Professor, St. John's University, Jamaica, NY; Clinical Coordinator, Jacobi Medical Center, Bronx, NY

Richard Oehler, MD

Assistant Professor, Director of Clinical Education, College of Medicine, Division of Infectious Disease, University of South Florida, Tampa, FL

Linda W Kam, PharmD BCPS

Infectious Disease Clinical Specialist, Director of PY2-Infectious Disease Pharmacy Residency, James A Haley Veterans Hospital, Tampa, FL

Igor Melnychuk, MD

Infectious Disease Fellow, College of Medicine, Division of Infectious Disease and International Medicine, University of South Florida

Reprints: Dr. Kam, James A Haley Veterans Hospital, 13000 Bruce B. Downs Blvd., Department 119, Tampa, FL 33612-4745, fax 813/979-3661, linda.kam{at}med.va.gov

OBJECTIVE: To describe emergent therapies, such as rifaximin, nitazoxanide, intravenous immunoglobulin (IVIG), tinidazole, tolevamer, and the possible use of a vaccine, in Clostridium difficile-associated disease (CDAD), one of the most common causes of diarrhea in hospitalized adults in North America.

DATA SOURCES: A literature search was performed using MEDLINE (1996-October 2006), PubMed (1996-October 2006), abstracts from Infectious Diseases Society of America (September 2006) and International Conference on Antimicrobial Agents and Chemotherapy (September 2006), Internet (October 2006), Genzyme product Web site (October 2006), and Romark Laboratories Web site (October 2006) using the terms Clostridium difficile, rifaximin, nitazoxanide, intravenous immunoglobulin, tolevamer, vaccine, and tinidazole.

STUDY SELECTION AND DATA EXTRACTION: Data presented in this article were selected based on clinical relevance and power of the studies. In vivo and in vitro studies supporting the use of drugs available for treatment of refractory CDAD were reviewed. Some of the information on new and emerging modalities was also included, although there were limited published data available.

DATA SYNTHESIS: Clinical trials evaluating the use of nitazoxanide and tolevamer for the treatment of CDAD have been published. Tinidazole use is based on structural similarities to metronidazole; however, clinical trials have not been conducted and the cost of this agent may be a limiting factor. The use of rifaximin and IVIG will require randomized clinical trials to establish their place in therapy. Limited information in the literature suggests that a vaccine may be effective for CDAD prevention.

CONCLUSIONS: CDAD is a debilitating disease with increasing treatment failure rates and recurrences using standard therapies. Clinicians need to look at other options to expand the available treatment arsenal in addition to placing a greater emphasis on prevention.

Key Words: Clostridium difficile, intravenous immunoglobulin, nitazoxanide, rifaximin, tinidazole, tolevamer, vaccine

Published Online, November 21, 2006. www.theannals.com, DOI 10.1345/aph.1H340

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