Whole Genome Sequencing Demonstrates Fidaxomicin is Superior to Vancomycin for Prevention of Clostridium difficile Relapse and Reinfection

Whole genome sequencing (WGS) was used to investigate whether fidaxomicin reduced Clostridium difficile recurrence in pivotal Phase III trials by preventing relapse of the same infection, reinfection with a new strain, or both. Paired isolates were available from 93/199 participants with recurrences (28 treated with fidaxomicin, 65 vancomycin). Given C. difficile evolutionary rates, samples =2 single nucleotide variants (SNVs) apart were considered relapses, samples >10 SNVs apart reinfection, and those with 3-10 SNVs (or without WGS) indeterminate in a competing risks survival analysis. Fidaxomicin reduced the risk of both relapse (competing risks hazard ratio(crHR)=0.40[95%CI 0.25-0.66] p=0.0003) and reinfection (crHR=0.33[0.11-1.01] p=0.05).