Effects of control interventions on Clostridium difficile infection in England: an observational study

被引：221

作者：

Dingle, Kate E. ^{[1
,2
,3
]}

Didelot, Xavier ^{[4
,5
]}

Quan, T. Phuong ^{[1
,2
,3
]}

Eyre, David W. ^{[1
,2
]}

Stoesser, Nicole ^{[1
,2
]}

Golubchik, Tanya ^{[1
,2
]}

Harding, Rosalind M. ^{[2
,6
]}

Wilson, Daniel J. ^{[1
,2
,7
]}

Griffiths, David ^{[1
,2
]}

Vaughan, Alison ^{[1
,2
]}

Finney, John M. ^{[1
,2
]}

Wyllie, David H. ^{[1
,2
,8
]}

Oakley, Sarah J. ^{[9
]}

Fawley, Warren N. ^{[10
,11
]}

Freeman, Jane ^{[10
,11
]}

Morris, Kirsti ^{[10
,11
]}

Martin, Jessica ^{[10
,11
]}

Howard, Philip ^{[12
]}

Gorbach, Sherwood ^{[13
,14
]}

Goldstein, Ellie J. C. ^{[15
]}

Citron, Diane M. ^{[15
]}

Hopkins, Susan ^{[3
,16
,17
,18
]}

Hope, Russell ^{[19
]}

Johnson, Alan P. ^{[3
,4
,5
,19
]}

Wilcox, Mark H. ^{[10
,11
]}

Peto, Timothy E. A. ^{[1
,2
,3
]}

Walker, A. Sarah ^{[1
,2
,3
]}

Crook, Derrick W. ^{[1
,2
,3
]}

机构：

[1] Univ Oxford, Nuffield Dept Clin Med, Oxford, England

[2] John Radcliffe Hosp, Oxford Biomed Res Ctr, NIHR, Oxford, England

[3] Univ Oxford, Partnership Publ Hlth England, NIHR Hlth Protect Res Unit Healthcare Associated, Oxford, England

[4] Imperial Coll London, Partnership Publ Hlth, Dept Infect Dis Epidemiol, London, England

[5] Imperial Coll London, Partnership Publ Hlth, NIHR Hlth Protect Res Healthcare Associated Infec, London, England

[6] Univ Oxford, Dept Zool, Oxford, England

[7] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[8] Publ Hlth England Acad Collaborating Ctr, Oxford, England

[9] Oxford Univ Hosp NHS Trust, Dept Microbiol, Oxford, England

[10] Leeds Teaching Hosp, Leeds, W Yorkshire, England

[11] Univ Leeds, Dept Microbiol, Leeds Gen Infirm, Leeds, W Yorkshire, England

[12] Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England

[13] Cubist Pharmaceut, Lexington, MA USA

[14] Tufts Univ, Sch Med, Boston, MA 02111 USA

[15] RM Alden Res Lab, Culver City, CA USA

[16] Publ Hlth England, Healthcare Associated Infect Antimicrobial Resist, London, England

[17] Royal Free London NHS Fdn Trust, London, England

[18] Publ Hlth England, London, England

[19] Publ Hlth England, Natl Infect Serv, Ctr Infect Dis Surveillance & Control, Dept Healthcare Associated Infect & Antimicrobial, London, England

来源：

LANCET INFECTIOUS DISEASES | 2017年 / 17卷 / 04期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

ANTIBIOTIC STEWARDSHIP; DIARRHEA; OUTBREAK; STRAIN; RISK; TRANSMISSION; METAANALYSIS; RESTRICTION; RESISTANCE; EMERGENCE;

D O I：

10.1016/S1473-3099(16)30514-X

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Background The control of Clostridium difficile infections is an international clinical challenge. The incidence of C difficile in England declined by roughly 80% after 2006, following the implementation of national control policies; we tested two hypotheses to investigate their role in this decline. First, if C difficile infection declines in England were driven by reductions in use of particular antibiotics, then incidence of C difficile infections caused by resistant isolates should decline faster than that caused by susceptible isolates across multiple genotypes. Second, if C difficile infection declines were driven by improvements in hospital infection control, then transmitted (secondary) cases should decline regardless of susceptibility. Methods Regional (Oxfordshire and Leeds, UK) and national data for the incidence of C difficile infections and antimicrobial prescribing data ( 1998- 2014) were combined with whole genome sequences from 4045 national and international C difficile isolates. Genotype ( multilocus sequence type) and fluoroquinolone susceptibility were determined from whole genome sequences. The incidence of C difficile infections caused by fluoroquinolone- resistant and fluoroquinolone- susceptible isolates was estimated with negative- binomial regression, overall and per genotype. Selection and transmission were investigated with phylogenetic analyses. Findings National fluoroquinolone and cephalosporin prescribing correlated highly with incidence of C difficile infections (cross- correlations > 0 . 88), by contrast with total antibiotic prescribing (cross-correlations < 0.59). Regionally, C difficile decline was driven by elimination of fluoroquinolone-resistant isolates (approximately 67% of Oxfordshire infections in September, 2006, falling to approximately 3% in February, 2013; annual incidence rate ratio 0.52, 95% CI 0.48-0.56 vs fluoroquinolone-susceptible isolates: 1.02, 0.97-1.08).C difficile infections caused by fluoroquinolone-resistant isolates declined in four distinct genotypes (p< 0.01).The regions of phylogenies containing fluoroquinolone-resistant isolates were short-branched and geographically structured, consistent with selection and rapid transmission.The importance of fluoroquinolone restriction over infection control was shown by significant declines in inferred secondary (transmitted) cases caused by fluoroquinolone-resistant isolates with or without hospital contact (p< 0.0001) versus no change in either group of cases caused by fluoroquinolone-susceptible isolates (p> 0.2). Interpretation Restricting fluoroquinolone prescribing appears to explain the decline in incidence of C difficile infections, above other measures, in Oxfordshire and Leeds, England.Antimicrobial stewardship should be a central component of C difficile infection control programmes. Funding UK Clinical Research Collaboration (Medical Research Council, Wellcome Trust, National Institute for Health Research); NIHR Oxford Biomedical Research Centre; NIHR Health Protection Research Unit on Healthcare Associated Infection and Antimicrobial Resistance (Oxford University in partnership with Public Health England [ PHE]), and on Modelling Methodology (Imperial College, London in partnership with PHE); and the Health Innovation Challenge Fund. Copyright (C) The Author(s).Published by Elsevier Ltd.This is an Open Access article under the CC BY license.

引用

页码：411 / 421

页数：11

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