Distinct clinical endpoints of Staphylococcus aureus bacteraemia complicate assessment of outcome

Clark D Russell; Karla Berry; George Cooper; Wynne Sim; Rui Shian Lee; Tze Yi Gan; William Donlon; Antonia Besu; Emily Heppenstall; Luke Tysall; Andrew Robb; Simon Dewar; Andrew Smith; Vance G Fowler Jr

doi:10.1093/cid/ciae281

Distinct clinical endpoints of Staphylococcus aureus bacteraemia complicate assessment of outcome

Clin Infect Dis. 2024 May 20:ciae281. doi: 10.1093/cid/ciae281. Online ahead of print.

Authors

Clark D Russell^{1

2}, Karla Berry³, George Cooper¹, Wynne Sim⁴, Rui Shian Lee⁴, Tze Yi Gan⁴, William Donlon⁴, Antonia Besu⁴, Emily Heppenstall², Luke Tysall², Andrew Robb⁵, Simon Dewar^{2

3}, Andrew Smith^{5

6}, Vance G Fowler Jr^{7

8}

Affiliations

¹ Centre for Inflammation Research, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, UK.
² Medical Microbiology, Royal Infirmary of Edinburgh, Edinburgh, UK.
³ Clinical Infection Research Group, Western General Hospital, Edinburgh, UK.
⁴ Edinburgh Medical School, The University of Edinburgh, Edinburgh, UK.
⁵ Scottish Microbiology Reference Laboratory, New Lister Building, Glasgow, UK.
⁶ College of Medical, Veterinary & Life Sciences, Glasgow Dental Hospital & School, University of Glasgow, Glasgow, UK.
⁷ Division of Infectious Diseases and International Health, Department of Medicine, Duke University School of Medicine, North Carolina, USA.
⁸ Duke Clinical Research Institute, North Carolina, USA.

PMID: 38767234
DOI: 10.1093/cid/ciae281

Abstract

Background: We aimed to test the hypothesis that development of metastatic infection represents a distinct clinical endpoint from death due to SAB.

Methods: We conducted a retrospective observational study of adults with SAB between 20/12/2019 and 23/08/2022 (n=464). Simple logistic regression, odds ratios, and z-scores were used to compare host, clinical and microbiologic features.

Results: Co-occurrence of attributable mortality and metastatic infection was infrequent. Charlson Comorbidity Index and age were strongly associated with attributable mortality, but not metastatic infection. We compared patients with fatal SAB (without clinically-apparent metastatic complications, 14·4% of cohort), metastatic SAB (without attributable mortality, 22·2%), neither complication (56·7%), and overlapping fatal/metastatic SAB (6·7%). Compared to SAB without complications, fatal SAB was specifically associated with older age and multi-morbidity. Metastatic SAB was specifically associated with community acquisition, persistent fever, persistent bacteraemia, and recurrence. Endocarditis was over-represented in the fatal/metastatic SAB overlap group, which shared patient characteristics with fatal SAB. In contrast to other (predominantly musculoskeletal) metastatic complications, endocarditis was associated with increased mortality, with death occurring in older multi-morbid patients later after SAB onset.

Conclusions: Patients with SAB experience distinct clinical endpoints: (i) early death, associated with multi-morbidity and age; (ii) metastatic (predominantly musculoskeletal) SAB; (iii) endocarditis, associated with late death occurring in older people with multi-morbidity, and (iv) bacteraemia without complications. These distinctions could be important for selecting appropriate outcomes in clinical trials: different interventions might be required to reduce mortality vs. improve clinical response in patients with metastatic SAB.

Keywords: Staphylococcus aureus; bacteraemia; clinical outcomes; clinical trials; metastatic infection; mortality.