Distinct Clinical Endpoints of Staphylococcus aureus Bacteraemia Complicate Assessment of Outcome

Abstract

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

Methods: We conducted a retrospective observational study of adults with SAB between 20 December 2019 and 23 August st2022 (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 bacteremia, 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 versus improve clinical response in patients with metastatic SAB.

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

Figure 1.

Components and patient characteristics of complicated SAB. A, Overlap in components of “complicated” SAB (IDSA and Fowler et al) co-occurring in the same patients. Numbers indicate the number of patients. This analysis was restricted to 290 patients with data recorded for follow-up blood cultures (performed within 48–96 h of index blood culture) and temperature on day 3 after index blood culture. Simple linear regression of (B) Charlson Comorbidity Index and (C) age with metastatic complications and attributable in-hospital mortality. Lines show regression lines and shaded areas show 95% confidence intervals. Abbreviations: IDSA, Infectious Diseases Society of America; SAB, Staphylococcus aureus bacteremia.

Figure 2.

Host, clinical, and microbiologic features of metastatic and fatal SAB. Features associated with (A) fatal SAB and (B) metastatic SAB compared to the group of patients with neither complication during index SAB episode. Volcano plot of log₂ odds ratio. Horizontal dotted lines indicate P = .05 and P = .01. Features are colored based on effect size and statistical significance (P < .05): positive association (orange), negative association (blue), or no association (grey). Features labelled in red font are specific to either metastatic or fatal SAB. Abbreviations: BC, blood culture; CCI, Charlson Comorbidity Index; CRP, C-reactive protein; CVC, central venous catheter; DM, diabetes mellitus; qSOFA, quick Sequential Organ Failure Assessment score; IDU, injection drug use; IV, intravenous; MI, myocardial infarction; PWID, person who injects drugs; SAB, Staphylococcus aureus bacteremia; SSTI, skin or soft tissue infection.

Figure 3.

Distinct clinical endpoints of SAB. A, Overlap between progression to attributable in-hospital mortality, endocarditis, other metastatic complications, or none of these complications during the index SAB episode. Overlap between sets indicates patients experienced all of the overlapping endpoints, for example, attributable mortality and endocarditis. Numbers indicate the number of patients. B, Unadjusted 365-day survival. Kaplan-Meier survival curve, shaded area represents 95% confidence interval for percentage surviving. Musculoskeletal metastatic complications were vertebral osteomyelitis, septic arthritis (native or prosthetic joint), and deep muscle abscesses. Abbreviation: SAB, Staphylococcus aureus bacteremia.