Clinical sub-phenotypes of Staphylococcus aureus bacteraemia
<p><strong>Background:</strong> Staphylococcus aureus bacteraemia (SAB) is a clinically heterogeneous disease. The ability to identify sub-groups of patients with shared traits (sub-phenotypes) is an unmet need that could allow patient stratification for clinical management and res...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2024
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| _version_ | 1811140360408137728 |
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| author | Swets, MC Bakk, Z Westgeest, AC Berry, K Cooper, G Sim, W Lee, RS Gan, TY Donlon, W Besu, A Heppenstall, E Tysall, L Dewar, S de Boer, M Fowler, VG Dockrell, DH Thwaites, GE Pujol, M Pallarès, N Tebé, C Carratalà, J Szubert, A Groeneveld, GH Russell, CD |
| author_facet | Swets, MC Bakk, Z Westgeest, AC Berry, K Cooper, G Sim, W Lee, RS Gan, TY Donlon, W Besu, A Heppenstall, E Tysall, L Dewar, S de Boer, M Fowler, VG Dockrell, DH Thwaites, GE Pujol, M Pallarès, N Tebé, C Carratalà, J Szubert, A Groeneveld, GH Russell, CD |
| author_sort | Swets, MC |
| collection | OXFORD |
| description | <p><strong>Background:</strong> Staphylococcus aureus bacteraemia (SAB) is a clinically heterogeneous disease. The ability to identify sub-groups of patients with shared traits (sub-phenotypes) is an unmet need that could allow patient stratification for clinical management and research. We aimed to test the hypothesis that clinically-relevant sub-phenotypes can be reproducibly identified amongst patients with SAB.</p>
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<p><strong>Methods:</strong> We studied three cohorts of hospitalised adults with monomicrobial SAB: a UK retrospective observational study (Edinburgh cohort, n=458), the UK ARREST randomised trial (n=758), and the Spanish SAFO randomised trial (n=214). Latent class analysis was used to identify sub-phenotypes using routinely-collected clinical data, without considering outcomes. Mortality and microbiologic outcomes were then compared between sub-phenotypes.</p>
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<p><Strong>Results:</strong> Included patients had predominantly methicillin-susceptible SAB (1366/1430,95.5%). We identified five distinct, reproducible clinical sub-phenotypes: (A) SAB associated with older age and comorbidity, (B) nosocomial intravenous catheter-associated SAB in younger people without comorbidity, (C) community-acquired metastatic SAB, (D) SAB associated with chronic kidney disease, and (E) SAB associated with injection drug use. Survival and microbiologic outcomes differed between the sub-phenotypes. 84-day mortality was highest in sub-phenotype A, and lowest in B and E. Microbiologic outcomes were worse in sub-phenotype C. In a secondary analysis of the ARREST trial, adjunctive rifampicin was associated with increased 84-day mortality in sub-phenotype B and improved microbiologic outcomes in sub-phenotype C.</p>
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<p><strong>Conclusions:</strong> We have identified reproducible and clinically-relevant sub-phenotypes within SAB, and provide proof-of-principle of differential treatment effects. Through clinical trial enrichment and patient stratification, these sub-phenotypes could contribute to a personalised medicine approach to SAB.</p> |
| first_indexed | 2024-09-25T04:20:45Z |
| format | Journal article |
| id | oxford-uuid:932de795-d8dd-4dc9-b33a-dc880635fcfe |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:20:45Z |
| publishDate | 2024 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:932de795-d8dd-4dc9-b33a-dc880635fcfe2024-08-01T16:22:04ZClinical sub-phenotypes of Staphylococcus aureus bacteraemiaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:932de795-d8dd-4dc9-b33a-dc880635fcfeEnglishSymplectic ElementsOxford University Press2024Swets, MCBakk, ZWestgeest, ACBerry, KCooper, GSim, WLee, RSGan, TYDonlon, WBesu, AHeppenstall, ETysall, LDewar, Sde Boer, MFowler, VGDockrell, DHThwaites, GEPujol, MPallarès, NTebé, CCarratalà, JSzubert, AGroeneveld, GHRussell, CD<p><strong>Background:</strong> Staphylococcus aureus bacteraemia (SAB) is a clinically heterogeneous disease. The ability to identify sub-groups of patients with shared traits (sub-phenotypes) is an unmet need that could allow patient stratification for clinical management and research. We aimed to test the hypothesis that clinically-relevant sub-phenotypes can be reproducibly identified amongst patients with SAB.</p> <br> <p><strong>Methods:</strong> We studied three cohorts of hospitalised adults with monomicrobial SAB: a UK retrospective observational study (Edinburgh cohort, n=458), the UK ARREST randomised trial (n=758), and the Spanish SAFO randomised trial (n=214). Latent class analysis was used to identify sub-phenotypes using routinely-collected clinical data, without considering outcomes. Mortality and microbiologic outcomes were then compared between sub-phenotypes.</p> <br> <p><Strong>Results:</strong> Included patients had predominantly methicillin-susceptible SAB (1366/1430,95.5%). We identified five distinct, reproducible clinical sub-phenotypes: (A) SAB associated with older age and comorbidity, (B) nosocomial intravenous catheter-associated SAB in younger people without comorbidity, (C) community-acquired metastatic SAB, (D) SAB associated with chronic kidney disease, and (E) SAB associated with injection drug use. Survival and microbiologic outcomes differed between the sub-phenotypes. 84-day mortality was highest in sub-phenotype A, and lowest in B and E. Microbiologic outcomes were worse in sub-phenotype C. In a secondary analysis of the ARREST trial, adjunctive rifampicin was associated with increased 84-day mortality in sub-phenotype B and improved microbiologic outcomes in sub-phenotype C.</p> <br> <p><strong>Conclusions:</strong> We have identified reproducible and clinically-relevant sub-phenotypes within SAB, and provide proof-of-principle of differential treatment effects. Through clinical trial enrichment and patient stratification, these sub-phenotypes could contribute to a personalised medicine approach to SAB.</p> |
| spellingShingle | Swets, MC Bakk, Z Westgeest, AC Berry, K Cooper, G Sim, W Lee, RS Gan, TY Donlon, W Besu, A Heppenstall, E Tysall, L Dewar, S de Boer, M Fowler, VG Dockrell, DH Thwaites, GE Pujol, M Pallarès, N Tebé, C Carratalà, J Szubert, A Groeneveld, GH Russell, CD Clinical sub-phenotypes of Staphylococcus aureus bacteraemia |
| title | Clinical sub-phenotypes of Staphylococcus aureus bacteraemia |
| title_full | Clinical sub-phenotypes of Staphylococcus aureus bacteraemia |
| title_fullStr | Clinical sub-phenotypes of Staphylococcus aureus bacteraemia |
| title_full_unstemmed | Clinical sub-phenotypes of Staphylococcus aureus bacteraemia |
| title_short | Clinical sub-phenotypes of Staphylococcus aureus bacteraemia |
| title_sort | clinical sub phenotypes of staphylococcus aureus bacteraemia |
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