Fidaxomicin: A Novel Macrocyclic Antibiotic for the Treatment of Clostridium difficile Infection

Tonya Crawford, Pharm.D; Emily Huesgen, Pharm.D; Larry Danziger, Pharm.D


Am J Health Syst Pharm. 2012;69(11):933-943. 

In This Article

Chemistry and Pharmacology

Fidaxomicin is a novel macrocyclic compound with an 18-membered lactone ring. Its molecular weight is 1058.04 Da, and its molecular formula is C52H74C12O18. The natural compound, originally discovered in the 1970s, was formerly known as lipiarmycin, tiacumicin B, OPT-80, PAR-101, and difimicin.[24–27] Fidaxomicin is derived from the fermentation products of Actinoplanes deccanensis and Dactylosporangium aurantiacum. After oral administration of a 400-mg dose of fidaxomicin, the active parent compound is hydrolyzed at the O-isobutyryl group in the fourth position to an active metabolite, OP-1118, in a 2:1 ratio (parent:metabolite).[28] Since fidaxomicin is not systemically absorbed, it is hypothesized that the conversion to OP-1118 occurs via hydrolysis in gastric acid or by the enzymatic activity of intestinal microsomes.[29]

Fidaxomicin inhibits bacterial transcription by binding to RNA polymerase, a large enzyme that consists of five subunits that comprise its core catalytic enzyme (α2 ββ' ω) and a separate sigma (σ) subunit responsible for promoter recognition.[30] Fidaxomicin inhibits the σ subunit.[31] This unique target site may explain the drug's limited spectrum of antimicrobial activity, since σ subunits differ among bacterial species.[32] To date, cross-resistance with other antibiotic classes has not been observed in in vitro studies.[33]


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