Whole-Genome Sequencing Demonstrates That Fidaxomicin Is Superior to Vancomycin for Preventing Reinfection and Relapse of Infection With Clostridium difficile

被引：44

作者：

Eyre, David W. ^{[1
]}

Babakhani, Farah ^{[2
]}

Griffiths, David ^{[1
]}

Seddon, Jaime ^{[2
]}

Elias, Carlos Del Ojo ^{[1
]}

Gorbach, Sherwood L. ^{[2
]}

Peto, Tim E. A. ^{[1
]}

Crook, DerrickW. ^{[1
]}

Walker, A. Sarah ^{[1
]}

机构：

[1] Univ Oxford, NIHR Oxford Biomed Res Ctr, Oxford OX1 2JD, England

[2] Optimer Pharmaceut, San Diego, CA USA

来源：

JOURNAL OF INFECTIOUS DISEASES | 2014年 / 209卷 / 09期

基金：

英国医学研究理事会; 英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

Clostridium difficile; recurrence; fidaxomicin; whole genome sequencing; RECURRENCE;

D O I：

10.1093/infdis/jit598

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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).

引用

页码：1446 / 1451

页数：6

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