title: Current and emerging management options for Clostridium difficile infection: what is the role of fidaxomicin?
abstract: Until recently, treatment of Clostridium difficile infection (CDI) was mainly limited to oral metronidazole and vancomycin, neither of which is optimal. Up to 25% of patients with CDI experience recurrence of infection within 30 days following treatment with these agents, while c. 45-65% of these patients experience further (and sometimes multiple) recurrences. Recurrent CDI represents a major treatment challenge for which new therapeutic options are sorely needed. Fidaxomicin is a first-in-class, oral macrocyclic antibiotic with targeted bactericidal activity against C. difficile and minimal effect on the constituents of the normal colonic microflora. This microflora-sparing activity allows for more rapid restoration of the normal colonic microflora in patients with CDI. In two separate, but almost identical, phase 3 clinical trials in which patients with CDI were treated with either fidaxomicin or vancomycin, fidaxomicin demonstrated superior clinical outcomes in comparison with the current best available treatment. While non-inferiority was demonstrated with respect to rates of clinical cure at end of treatment, significantly fewer fidaxomicin-treated patients experienced disease recurrence, which translated into clinically significant improvements in sustained clinical cure. Subsequent sub-population analyses suggest that these benefits extend to older patients, patients with severe CDI, renally impaired patients and patients with a prior episode of CDI. For CDI patients receiving concomitant antibiotics, fidaxomicin achieved significantly better rates of clinical cure and sustained clinical cure than vancomycin recipients. Fidaxomicin has a safety profile similar to oral vancomycin and appears generally well tolerated. Fidaxomicin represents an important addition to current treatment options for CDI.
authors.affiliation: 1st Department of Internal Medicine, Clinical Trials Centre Cologne, ZKS Köln, BMBF 01KN1106, Center for Integrated Oncology CIO Köln Bonn, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases and German Centre for Infection Research, University of Cologne, Cologne, Germany. oliver.cornely@ctuc.de
authors.forename: O A
authors.initials: OA
authors.lastname: Cornely
mesh_terms: D000617:Aminoglycosides / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016360:Clostridioides difficile / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000188:drug therapy*; D000077732:Fidaxomicin; D006801:Humans; D012008:Recurrence; D014640:Vancomycin / Q000627:therapeutic use
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D014640:Vancomycin; D000077732:Fidaxomicin