Whole-genome sequencing demonstrates that fidaxomicin is superior to vancomycin for preventing reinfection and relapse of infection with Clostridium difficile.
Whole-genome sequencing was used to determine whether the reductions in recurrence of Clostridium difficile infection observed with fidaxomicin in pivotal phase 3 trials occurred by preventing relapse of the same infection, by preventing reinfection with a new strain, or by preventing both outcomes. Paired isolates of C. difficile were available from 93 of 199 participants with recurrences (28 were treated with fidaxomicin, and 65 were treated with vancomycin). Given C. difficile evolutionary rates, paired samples ≤2 single-nucleotide variants (SNVs) apart were considered relapses, paired samples >10 SNVs apart were considered reinfection, and those 3-10 SNVs apart (or without whole-genome sequences) were considered indeterminate in a competing risks survival analysis. Fidaxomicin reduced the risk of both relapse (competing risks hazard ratio [HR], 0.40 [95% confidence interval {CI}, .25-.66]; P = .0003) and reinfection (competing risks HR, 0.33 [95% CI, 0.11-1.01]; P = .05).
NIHR Oxford Biomedical Research Centre, University of Oxford, United Kingdom.
David W
DW
Eyre
Farah
F
Babakhani
David
D
Griffiths
Jaime
J
Seddon
Carlos
C
Del Ojo Elias
Sherwood L
SL
Gorbach
Tim E A
TE
Peto
Derrick W
DW
Crook
A Sarah
AS
Walker
D000617:Aminoglycosides / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016360:Clostridioides difficile / Q000235:genetics* / Q000302:isolation & purification; D003015:Clostridium Infections / Q000188:drug therapy / Q000382:microbiology* / Q000517:prevention & control*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004311:Double-Blind Method; D024881:Drug Resistance, Bacterial; D000077732:Fidaxomicin; D016680:Genome, Bacterial; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D055502:Secondary Prevention; D017422:Sequence Analysis, DNA; D014640:Vancomycin / Q000627:therapeutic use*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D014640:Vancomycin; D000077732:Fidaxomicin
Clostridium difficile; fidaxomicin; recurrence; whole genome sequencing