Clinical Subphenotypes of Staphylococcus aureus Bacteremia.

Autor:	Swets MC; Department of Infectious Diseases, Leiden University Medical Center, Leiden University, Leiden, The Netherlands.; Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom., Bakk Z; Department of Methodology and Statistics, Leiden University, Leiden, The Netherlands., Westgeest AC; Department of Infectious Diseases, Leiden University Medical Center, Leiden University, Leiden, The Netherlands., Berry K; Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom.; Clinical Infection Research Group, Western General Hospital, Edinburgh, United Kingdom., Cooper G; Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom., Sim W; Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom., Lee RS; Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom., Gan TY; Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom., Donlon W; Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom., Besu A; Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom., Heppenstall E; Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom., Tysall L; Medical Microbiology, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom., Dewar S; Clinical Infection Research Group, Western General Hospital, Edinburgh, United Kingdom.; Medical Microbiology, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom., de Boer M; Department of Infectious Diseases, Leiden University Medical Center, Leiden University, Leiden, The Netherlands.; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands., Fowler VG Jr; Division of Infectious Diseases and International Health, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.; Duke Clinical Research Institute, Durham, North Carolina, USA., Dockrell DH; Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom., Thwaites GE; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Pujol M; Department of Infectious Diseases, Bellvitge University Hospital, L´Hospitalet de LLobregat, Barcelona, Spain.; Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain., Pallarès N; Biostatistics Support and Research Unit, Germans Trias i Pujol Research Institute and Hospital, Badalona, Spain.; Department of Basic Clinical Practice, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain., Tebé C; Biostatistics Support and Research Unit, Germans Trias i Pujol Research Institute and Hospital, Badalona, Spain., Carratalà J; Department of Infectious Diseases, Bellvitge University Hospital, L´Hospitalet de LLobregat, Barcelona, Spain.; Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.; Department of Clinical Sciences, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain., Szubert A; MRC Clinical Trials Unit, University College London, London, United Kingdom., Groeneveld GH; Department of Infectious Diseases, Leiden University Medical Center, Leiden University, Leiden, The Netherlands.; Department of Internal Medicine-Acute Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands., Russell CD; Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom.; Medical Microbiology, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2024 Nov 22; Vol. 79 (5), pp. 1153-1161.
DOI:	10.1093/cid/ciae338
Abstrakt:	Background: Staphylococcus aureus bacteremia (SAB) is a clinically heterogeneous disease. The ability to identify subgroups of patients with shared traits (subphenotypes) is an unmet need to allow patient stratification for clinical management and research. We aimed to test the hypothesis that clinically relevant subphenotypes can be reproducibly identified among patients with SAB. Methods: We studied 3 cohorts of adults with monomicrobial SAB: a UK retrospective observational study (Edinburgh cohort, n = 458), the UK ARREST trial (n = 758), and the Spanish SAFO trial (n = 214). Latent class analysis was used to identify subphenotypes using routinely collected clinical data without considering outcomes. Mortality and microbiologic outcomes were then compared between subphenotypes. Results: Included patients had predominantly methicillin-susceptible SAB (1366 of 1430, 95.5%). We identified 5 distinct, reproducible clinical subphenotypes: (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 subphenotypes. Mortality was highest in subphenotype A and lowest in subphenotypes B and E. Microbiologic outcomes were worse in subphenotype C. In a secondary analysis of the ARREST trial, adjunctive rifampicin was associated with increased mortality in subphenotype B and improved microbiologic outcomes in subphenotype C. Conclusions: We have identified reproducible and clinically relevant subphenotypes within SAB and provide proof of principle of differential treatment effects. Through clinical trial enrichment and patient stratification, these subphenotypes could contribute to a personalized medicine approach to SAB. Competing Interests: Potential conflicts of interest . C. T. reports speaker fees from Gedeon Richter. V. G. F. reports grants/research support from Astra Zeneca, MedImmune, Merck, ContraFect, Karius, Genentech, Regeneron, and Basilea; serving as a paid consultant for Astra Zeneca, GSK, Armata, Debiopharm, Genentech, Basilea Affinergy, Janssen, ContraFect, and Destiny; and royalties from UpToDate. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze:	MEDLINE
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