Effects of control interventions on Clostridium difficile infection in England: an observational study
Background<br/> The control of Clostridium difficile infections (CDI) is an international clinical challenge. Uniquely, CDI incidence in England declined by ~80% after 2006, following implementation of national control policies; we investigated their role in this decline. This study tested two...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
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Lancet
2017
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| _version_ | 1797100899591520256 |
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| author | Dingle, K Didelot, X Quan, T Eyre, D Stoesser, N Golubchik, T Harding, R Wilson, D Griffiths, D Vaughan, A Finney, J Wyllie, D Oakley, S Fawley, W Freeman, J Morris, K Martin, J Howard, P Gorbach, S Goldstein, E Citron, D Hopkins, S Hope, R Johnson, A Wilcox, M Peto, T Walker, A Crook, D |
| author_facet | Dingle, K Didelot, X Quan, T Eyre, D Stoesser, N Golubchik, T Harding, R Wilson, D Griffiths, D Vaughan, A Finney, J Wyllie, D Oakley, S Fawley, W Freeman, J Morris, K Martin, J Howard, P Gorbach, S Goldstein, E Citron, D Hopkins, S Hope, R Johnson, A Wilcox, M Peto, T Walker, A Crook, D |
| author_sort | Dingle, K |
| collection | OXFORD |
| description | Background<br/> The control of Clostridium difficile infections (CDI) is an international clinical challenge. Uniquely, CDI incidence in England declined by ~80% after 2006, following implementation of national control policies; we investigated their role in this decline. This study tested two hypotheses. First, if CDI declines in England were driven by changes in use of particular antibiotics, then incidence of CDI caused by resistant isolates should decline faster than that caused by susceptible isolates across multiple genotypes (defined by multilocus sequence type (ST)). Second, if CDI declines were driven by improvements in hospital infection control, then transmitted (secondary) cases should decline regardless of susceptibility. <br/><br/>Methods<br/> Regional and national CDI incidence and antimicrobial prescribing data (1998-2014) were combined with whole genome sequences (WGS) from 4045 national and international C. difficile isolates. Genotype (multilocus sequence type) and fluoroquinolone susceptibility were determined from WGS. The incidence of CDI caused by fluoroquinolone-resistant and -susceptible isolates was estimated using negative-binomial regression, overall and per genotype. Selection and transmission were investigated using phylogenetic analyses. <br/><br/>Findings<br/> National fluoroquinolone and cephalosporin prescribing correlated highly with CDI incidence (cross-correlations>0·88), in contrast to total antibiotic prescribing (cross-correlations<0·59). Regionally, CDI decline was driven by elimination of fluoroquinolone-resistant isolates (~67% of Oxfordshire cases in September 2006, ~3% in February 2013; annual incidence rate ratio: 0·52, (95%CI 0·48,0·56), versus fluoroquinolone-susceptible isolates: 1·02, (0·97,1·08)). CDI 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 demonstrated 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). <br/><br/>Interpretation<br/> Restricting fluoroquinolone prescribing appears to explain the decline in CDI incidence, above other measures, in Oxfordshire and Leeds, England. Antimicrobial stewardship should be a central component of CDI control programs. |
| first_indexed | 2024-03-07T05:44:14Z |
| format | Journal article |
| id | oxford-uuid:e6a57699-8129-4ba0-a16a-bea0b5ef6202 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T05:44:14Z |
| publishDate | 2017 |
| publisher | Lancet |
| record_format | dspace |
| spelling | oxford-uuid:e6a57699-8129-4ba0-a16a-bea0b5ef62022022-03-27T10:32:45ZEffects of control interventions on Clostridium difficile infection in England: an observational studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e6a57699-8129-4ba0-a16a-bea0b5ef6202Symplectic Elements at OxfordLancet2017Dingle, KDidelot, XQuan, TEyre, DStoesser, NGolubchik, THarding, RWilson, DGriffiths, DVaughan, AFinney, JWyllie, DOakley, SFawley, WFreeman, JMorris, KMartin, JHoward, PGorbach, SGoldstein, ECitron, DHopkins, SHope, RJohnson, AWilcox, MPeto, TWalker, ACrook, DBackground<br/> The control of Clostridium difficile infections (CDI) is an international clinical challenge. Uniquely, CDI incidence in England declined by ~80% after 2006, following implementation of national control policies; we investigated their role in this decline. This study tested two hypotheses. First, if CDI declines in England were driven by changes in use of particular antibiotics, then incidence of CDI caused by resistant isolates should decline faster than that caused by susceptible isolates across multiple genotypes (defined by multilocus sequence type (ST)). Second, if CDI declines were driven by improvements in hospital infection control, then transmitted (secondary) cases should decline regardless of susceptibility. <br/><br/>Methods<br/> Regional and national CDI incidence and antimicrobial prescribing data (1998-2014) were combined with whole genome sequences (WGS) from 4045 national and international C. difficile isolates. Genotype (multilocus sequence type) and fluoroquinolone susceptibility were determined from WGS. The incidence of CDI caused by fluoroquinolone-resistant and -susceptible isolates was estimated using negative-binomial regression, overall and per genotype. Selection and transmission were investigated using phylogenetic analyses. <br/><br/>Findings<br/> National fluoroquinolone and cephalosporin prescribing correlated highly with CDI incidence (cross-correlations>0·88), in contrast to total antibiotic prescribing (cross-correlations<0·59). Regionally, CDI decline was driven by elimination of fluoroquinolone-resistant isolates (~67% of Oxfordshire cases in September 2006, ~3% in February 2013; annual incidence rate ratio: 0·52, (95%CI 0·48,0·56), versus fluoroquinolone-susceptible isolates: 1·02, (0·97,1·08)). CDI 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 demonstrated 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). <br/><br/>Interpretation<br/> Restricting fluoroquinolone prescribing appears to explain the decline in CDI incidence, above other measures, in Oxfordshire and Leeds, England. Antimicrobial stewardship should be a central component of CDI control programs. |
| spellingShingle | Dingle, K Didelot, X Quan, T Eyre, D Stoesser, N Golubchik, T Harding, R Wilson, D Griffiths, D Vaughan, A Finney, J Wyllie, D Oakley, S Fawley, W Freeman, J Morris, K Martin, J Howard, P Gorbach, S Goldstein, E Citron, D Hopkins, S Hope, R Johnson, A Wilcox, M Peto, T Walker, A Crook, D Effects of control interventions on Clostridium difficile infection in England: an observational study |
| title | Effects of control interventions on Clostridium difficile infection in England: an observational study |
| title_full | Effects of control interventions on Clostridium difficile infection in England: an observational study |
| title_fullStr | Effects of control interventions on Clostridium difficile infection in England: an observational study |
| title_full_unstemmed | Effects of control interventions on Clostridium difficile infection in England: an observational study |
| title_short | Effects of control interventions on Clostridium difficile infection in England: an observational study |
| title_sort | effects of control interventions on clostridium difficile infection in england an observational study |
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