QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Résumé Extracto Full Text PDF Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Articles Ahead of Print [Order Reprint] Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sullivan, K. M Articles by Spooner, L. M Search for Related Content PubMed PubMed Citation Articles by Sullivan, K. M Articles by Spooner, L. M

NEW DRUG DEVELOPMENTS

Fidaxomicin: A Macrocyclic Antibiotic for the Management of Clostridium difficile Infection

Assistant Professor of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences, Worcester, MA

Linda M Spooner, PharmD BCPS with Added Qualifications in Infectious Diseases

Associate Professor of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences

Reprints: Dr. Sullivan, Massachusetts College of Pharmacy and Health Sciences, 19 Foster St., Worcester, MA 01608, fax 508/756-8715, Karyn.sullivan{at}mcphs.edu

OBJECTIVE: To evaluate the efficacy and safety of fidaxomicin for the treatment of Clostridium difficile infection.

DATA SOURCES: Literature retrieval was accessed through MEDLINE (1966-January 2010) and International Pharmaceutical Abstracts (1970-January 2010) using the terms OPT-80, difimicin, PAR-101, fidaxomicin, tiacumicin, lipiarmycin, and Clostridium difficile. In addition, reference citations from publications identified were reviewed.

STUDY SELECTION AND DATA EXTRACTION: All articles published in English that were identified from the data sources were evaluated and pertinent information was included.

DATA SYNTHESIS: Fidaxomicin is an 18-membered macrocyclic antibiotic with activity against gram-positive aerobes and anaerobes, including C. difficile. Microbiologic studies comparing in vitro activity of fidaxomicin with that of metronidazole and vancomycin have shown good activity against all strains of C. difficile tested; however, minimum inhibitory concentrations were consistently lower for fidaxomicin. Studies showed that fidaxomicin lacks activity against gram-negative pathogens, thereby preserving normal gastrointestinal flora. Small pharmacokinetic trials have shown that fidaxomicin administration leads to low concentrations in plasma, high concentrations in stool, and a postantibiotic effect of greater than 24 hours, all of which are potentially advantageous characteristics for treating C. difficile infection. Data from 2 Phase 2A trials and 1 Phase 3 (multicenter, randomized, double-blind) trial suggest that fidaxomicin is effective for the treatment of mild-to-moderate C. difficile infection at a dose of 200 mg orally every 12 hours. Limited early results from the Phase 3 trial showed favorable outcomes for fidaxomicin when compared to oral vancomycin. Overall, fidaxomicin has been well tolerated to date.

CONCLUSIONS: The activity of fidaxomicin and limited clinical data suggest that it may have a future role in the treatment of mild-to-moderate C. difficile infection. The complete pharmacokinetic/pharmacodynamic profile, safety, and place in therapy have yet to be determined as trials comparing this agent to vancomycin are forthcoming.

Key Words: Clostridium difficile, difimicin, fidaxomicin, OPT-80

Published Online, January 13, 2010. www.theannals.com, DOI 10.1345/aph.1M351