Distinct clinical endpoints of Staphylococcus aureus bacteraemia complicate assessment of outcome.

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.

Clinical sub-phenotypes of Staphylococcus aureus bacteraemia.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Documentation of atrial fibrillation among non-conveyed ambulance patients: a new primary prevention opportunity?

Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is a significant risk factor for stroke. Prescription of oral anticoagulant (OAC) medication reduces the risk of AF-related stroke by 64% - yet over 400,000 people in England have undiagnosed (and therefore untreated) AF.Emergency medical services (EMS) encounter a wide range of patients, some of whom may not engage with other healthcare services. AF may be detected by EMS in connection with the cause of the call, or as an incidental finding. While EMS are not traditionally utilised for public health screening, they may offer an opportunity to identify patients with undiagnosed or untreated AF and refer onward.This study aimed to explore what proportion of patients seen by EMS who were not transported to hospital had AF and to estimate how many would potentially benefit from OAC. Methods: A retrospective service evaluation was conducted using routinely collected data from a large UK regional ambulance service. The sample included adults attended by EMS on the 15th of each month in 2019, who were not transported to hospital and where an electrocardiogram was recorded. Of those with AF, we calculated the proportion in whom this was possibly new and report whether OAC was prescribed. Results: There were 859 patients who met the inclusion criteria, of whom 91 (11%) had AF documented. Of the 91 patients with AF, 23 (25%) had no documented history of AF or OAC prescription, so were potentially new diagnoses of AF, who would benefit from consideration of OAC therapy. Conclusion: The EMS assessment offers an opportunity for AF to be identified in patients who were not transported to hospital. EMS may have a role in primary prevention of harm, including stroke, by identifying and referring patients with AF for consideration of OAC.