Relationship between bacterial strain type, host biomarkers, and mortality in Clostridium difficile infection.
<p><strong>Background.</strong> Despite substantial interest in biomarkers, their impact on clinical outcomes and variation with bacterial strain has rarely been explored using integrated databases.</p> <p><strong>Methods.</strong> From September 2006 to May...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Oxford University Press
2013
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| _version_ | 1797086253812809728 |
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| author | Walker, A Eyre, D Wyllie, D Dingle, K Griffiths, D Shine, B Oakley, S O'Connor, L Finney, J Vaughan, A Crook, D Wilcox, M Peto, T |
| author_facet | Walker, A Eyre, D Wyllie, D Dingle, K Griffiths, D Shine, B Oakley, S O'Connor, L Finney, J Vaughan, A Crook, D Wilcox, M Peto, T |
| author_sort | Walker, A |
| collection | OXFORD |
| description | <p><strong>Background.</strong> Despite substantial interest in biomarkers, their impact on clinical outcomes and variation with bacterial strain has rarely been explored using integrated databases.</p> <p><strong>Methods.</strong> From September 2006 to May 2011, strains isolated from <em>Clostridium difficile</em> toxin enzyme immunoassay (EIA)–positive fecal samples from Oxfordshire, United Kingdom (approximately 600 000 people) underwent multilocus sequence typing. Fourteen-day mortality and levels of 15 baseline biomarkers were compared between consecutive <em>C. difficile</em> infections (CDIs) from different clades/sequence types (STs) and EIA-negative controls using Cox and normal regression adjusted for demographic/clinical factors.</p> <p><strong>Results.</strong> Fourteen-day mortality was 13% in 2222 adults with 2745 EIA-positive samples (median, 78 years) vs 5% in 20 722 adults with 27 550 EIA-negative samples (median, 74 years) (absolute attributable mortality, 7.7%; 95% CI, 6.4%–9.0%). Mortality was highest in clade 5 CDIs (25% [16 of 63]; polymerase chain reaction (PCR) ribotype 078/ST 11), then clade 2 (20% [111 of 560]; 99% PCR ribotype 027/ST 1) versus clade 1 (12% [137 of 1168]; adjusted P < .0001). Within clade 1, 14-day mortality was only 4% (3 of 84) in ST 44 (PCR ribotype 015) (adjusted <em>P</em> = .05 vs other clade 1). Mean baseline neutrophil counts also varied significantly by genotype: 12.4, 11.6, and 9.5 × 10<sup>9</sup> neutrophils/L for clades 5, 2 and 1, respectively, vs 7.0 × 10<sup>9</sup> neutrophils/L in EIA-negative controls (<em>P</em> < .0001) and 7.9 × 10<sup>9</sup> neutrophils/L in ST 44 (<em>P</em> = .08). There were strong associations between <em>C. difficile</em>-type-specific effects on mortality and neutrophil/white cell counts (rho = 0.48), C-reactive-protein (rho = 0.43), eosinophil counts (rho = −0.45), and serum albumin (rho = −0.47). Biomarkers predicted 30%–40% of clade-specific mortality differences.</p> <p><strong>Conclusions.</strong> <em>C. difficile</em> genotype predicts mortality, and excess mortality correlates with genotype-specific changes in biomarkers, strongly implicating inflammatory pathways as a major influence on poor outcome after CDI. PCR ribotype 078/ST 11 (clade 5) leads to severe CDI; thus ongoing surveillance remains essential.</p> |
| first_indexed | 2024-03-07T02:19:30Z |
| format | Journal article |
| id | oxford-uuid:a36ae4ab-e668-4c66-9dbc-fe056b7ea967 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:19:30Z |
| publishDate | 2013 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:a36ae4ab-e668-4c66-9dbc-fe056b7ea9672022-03-27T02:26:49ZRelationship between bacterial strain type, host biomarkers, and mortality in Clostridium difficile infection.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a36ae4ab-e668-4c66-9dbc-fe056b7ea967EnglishSymplectic Elements at OxfordOxford University Press2013Walker, AEyre, DWyllie, DDingle, KGriffiths, DShine, BOakley, SO'Connor, LFinney, JVaughan, ACrook, DWilcox, MPeto, T<p><strong>Background.</strong> Despite substantial interest in biomarkers, their impact on clinical outcomes and variation with bacterial strain has rarely been explored using integrated databases.</p> <p><strong>Methods.</strong> From September 2006 to May 2011, strains isolated from <em>Clostridium difficile</em> toxin enzyme immunoassay (EIA)–positive fecal samples from Oxfordshire, United Kingdom (approximately 600 000 people) underwent multilocus sequence typing. Fourteen-day mortality and levels of 15 baseline biomarkers were compared between consecutive <em>C. difficile</em> infections (CDIs) from different clades/sequence types (STs) and EIA-negative controls using Cox and normal regression adjusted for demographic/clinical factors.</p> <p><strong>Results.</strong> Fourteen-day mortality was 13% in 2222 adults with 2745 EIA-positive samples (median, 78 years) vs 5% in 20 722 adults with 27 550 EIA-negative samples (median, 74 years) (absolute attributable mortality, 7.7%; 95% CI, 6.4%–9.0%). Mortality was highest in clade 5 CDIs (25% [16 of 63]; polymerase chain reaction (PCR) ribotype 078/ST 11), then clade 2 (20% [111 of 560]; 99% PCR ribotype 027/ST 1) versus clade 1 (12% [137 of 1168]; adjusted P < .0001). Within clade 1, 14-day mortality was only 4% (3 of 84) in ST 44 (PCR ribotype 015) (adjusted <em>P</em> = .05 vs other clade 1). Mean baseline neutrophil counts also varied significantly by genotype: 12.4, 11.6, and 9.5 × 10<sup>9</sup> neutrophils/L for clades 5, 2 and 1, respectively, vs 7.0 × 10<sup>9</sup> neutrophils/L in EIA-negative controls (<em>P</em> < .0001) and 7.9 × 10<sup>9</sup> neutrophils/L in ST 44 (<em>P</em> = .08). There were strong associations between <em>C. difficile</em>-type-specific effects on mortality and neutrophil/white cell counts (rho = 0.48), C-reactive-protein (rho = 0.43), eosinophil counts (rho = −0.45), and serum albumin (rho = −0.47). Biomarkers predicted 30%–40% of clade-specific mortality differences.</p> <p><strong>Conclusions.</strong> <em>C. difficile</em> genotype predicts mortality, and excess mortality correlates with genotype-specific changes in biomarkers, strongly implicating inflammatory pathways as a major influence on poor outcome after CDI. PCR ribotype 078/ST 11 (clade 5) leads to severe CDI; thus ongoing surveillance remains essential.</p> |
| spellingShingle | Walker, A Eyre, D Wyllie, D Dingle, K Griffiths, D Shine, B Oakley, S O'Connor, L Finney, J Vaughan, A Crook, D Wilcox, M Peto, T Relationship between bacterial strain type, host biomarkers, and mortality in Clostridium difficile infection. |
| title | Relationship between bacterial strain type, host biomarkers, and mortality in Clostridium difficile infection. |
| title_full | Relationship between bacterial strain type, host biomarkers, and mortality in Clostridium difficile infection. |
| title_fullStr | Relationship between bacterial strain type, host biomarkers, and mortality in Clostridium difficile infection. |
| title_full_unstemmed | Relationship between bacterial strain type, host biomarkers, and mortality in Clostridium difficile infection. |
| title_short | Relationship between bacterial strain type, host biomarkers, and mortality in Clostridium difficile infection. |
| title_sort | relationship between bacterial strain type host biomarkers and mortality in clostridium difficile infection |
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