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Whole-Genome Sequencing Demonstrates That Fidaxomicin Is Superior to Vancomycin for Preventing Reinfection and Relapse of Infection With Clostridium difficile
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Whole-Genome Sequencing Demonstrates That Fidaxomicin Is Superior to Vancomycin for Preventing Reinfection and Relapse of Infection With Clostridium difficile
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Journal Article
Whole-Genome Sequencing Demonstrates That Fidaxomicin Is Superior to Vancomycin for Preventing Reinfection and Relapse of Infection With Clostridium difficile
2014
Overview
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).
Publisher
Oxford University Press
Subject
Aminoglycosides - therapeutic use
/ Anti-Bacterial Agents - therapeutic use
/ BACTERIA
/ Biological and medical sciences
/ Clostridioides difficile - genetics
/ Clostridioides difficile - isolation & purification
/ Clostridium Infections - drug therapy
/ Clostridium Infections - microbiology
/ Clostridium Infections - prevention & control
/ Fundamental and applied biological sciences. Psychology
/ Genomes
/ Humans
/ Polymorphism, Single Nucleotide
/ Relapse
