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

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

Disclosures

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

In This Article

Resistance

Fidaxomicin resistance in vivo has not been reported.[45–48] Cross-resistance among fidaxomicin, macrolides, β-lactams, lincosamides, aminoglycosides, and rifampin has also not been observed.[33] In vitro studies using serial passage methods suggest that the frequency of spontaneous mutations in the presence of fidaxomicin is low (less than 3 × 10−8).[33,37] Genetic mapping of fidaxomicin-resistant colonies demonstrated that a point mutation in the β' subunit of RNA polymerase is responsible for fidaxomicin resistance.[31] The difference between the resistance site (the β' subunit of the core enzyme) and the antibiotic binding site (the σ subunit) may be explained by the close physical proximity of the two subunits.

Although the frequency of mutations to fidaxomicin appears to be low, this observation does not necessarily imply that fidaxomicin carries less risk of resistance compared with other antibiotics. Clinical experience with fidaxomicin among the general population is needed to accurately assess its risk of conferring resistance.

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