Fidaxomicin: a macrocyclic antibiotic for the management of Clostridium difficile infection.
OBJECTIVE
To evaluate the efficacy and safety of fidaxomicin for the treatment of Clostridium difficile infection.


METHODS
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.


METHODS
All articles published in English that were identified from the data sources were evaluated and pertinent information was included.


RESULTS
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.
Sullivan
Karyn M
KM
Massachusetts College of Pharmacy and Health Sciences, Worcester, MA, USA. Karyn.sullivan@mcphs.edu
Spooner
Linda M
LM
D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016360:Clostridioides difficile / Q000187:drug effects; D003015:Clostridium Infections / Q000188:drug therapy* / Q000382:microbiology; D006027:Glycosides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008826:Microbial Sensitivity Tests; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D006027:Glycosides; C487655:OPT 80; D014640:Vancomycin