Outcomes and measurements

The primary outcome was number of days alive and free of systemic inflammatory response syndrome (SIRS) (defined as meeting <2 simultaneous SIRS criteria on a calendar day) ≤14 days post-randomization (Appendix S2). The secondary outcomes were: (i) all-cause mortality at 14, 42 and 90 days; (ii) time to first resolution of SIRS (number of days until the patient meets <2 simultaneous SIRS criteria); (iii) proportion with microbiological relapse by Day 90 (positive blood culture for S. aureus ≥72 h after a preceding negative culture); (iv) proportion with microbiological treatment failure by Day 90 (positive sterile site culture for S. aureus ≥14 days after randomization); (v) number of surgical procedures needed to achieve source control; (vi) duration of IV antibiotic treatment; (vii) C. difficile-associated diarrhoea (three or more loose stools per day with a positive laboratory test for C. difficile toxin); (viii) all cause diarrhoea (three or more loose stools per day); and (ix) time to a ≥50% decrease in C-reactive protein (CRP) in the first 14 days post-randomization (excluding participants missing a baseline CRP level).

Routine haematological parameters, repeat cultures, surgery for source control for S. aureus, patient progress and treatment were gathered from medical records, pathology results and treating teams onto an electronic case report form on Days 1, 3, 7, 10 and 14 and then weekly thereafter if an inpatient, and out to 90 days post-randomization (REDCap database).¹⁷ All-cause mortality data were collected through participant contact at 90 days or retrieved from medical records. Adverse events (AEs) were captured daily whilst an inpatient and up until 90 days post-randomization. All serious adverse events (SAEs) as defined in the protocol¹⁴ to any of the study drugs reported.