Table 1.

Published Studies Describing Oral Antibiotic Therapy for Uncomplicated or “Low-risk” S. aureus Bacteremia

Title (Author, Year, Title)	Study Design	Number and Category of Participants	Study Intervention	Study Outcome	Limitations
Willekens et al 2019, EOS to linezolid for low-risk patients with Staphylococcus aureus bloodstream infections. [15]	Prospective, single-center cohort study, non-randomized	152 low-risk SAB patients (45 EOS, 90 IV) 11% MRSA	EOS to oral linezolid 600 mg BD on day 3–9 of treatment or continued IV treatment	No significant difference in 90 d relapse or 30 d all-cause mortality between groups. Less time in hospital was required for the EOS group (8 d vs 19 d) EOS using linezolid gave similar clinical outcomes to continued IV treatment, and reduced hospital stay. Trend to improved outcomes (2% 30-day mortality vs 13%)	A relatively small sample size limited the power of the study
Thorlacius-Ussing et al 2019, Efficacy of 7 and 14 days of antibiotic treatment in uncomplicated Staphylococcus aureus bacteremia (SAB7). [17]	Randomised open label multicentre trial	Currently enrolling	RCT evaluating efficacy of 7 versus 14 d of antibiotic treatment for uncomplicated SAB. Antibiotic treatment and dosage are as per local or national guidelines.	No current update available.	…
Bupha-Intr et al 2020, Efficacy of EOS with beta-lactams for low-risk Staphylococcus aureus bacteraemia. [12]	Retrospective, single-centre, cohort study, non-randomised	100 low-risk SAB participants (84 EOS, 16 IV) 5% MRSA	EOS after median 5 d of IV and compared to patients who continued IV treatment. 86% of these received oral beta-lactams eg 1 g flucloxacillin TDS	Only 1 EOS incorrectly triaged patient relapsed in 90 d. No deaths attributable to SAB	These 100 were of 469 total patients. ‘Low-risk” included those with fever >48 h. EOS was standard of care, so the 16 IV participants were exceptions eg due to inability to absorb the antibiotic. Low MRSA (5%), a risk-factor for poor outcomes, were included in the cohort. Almost all participants suffered from line infections. Limited meaningful statistical comparisons due to the reduced size of the IV therapy group. No comment on side effects of either regimen
Kaasch et al 2023, EOS therapy in low-risk Staphylococcus aureus bloodstream infection (SABATO). [9]	Prospective, multi-centre, randomised, open label	213 low-risk SAB participants (108 EOS, 103 IV) 5% MRSA	EOS at Day 5–7 of treatment or standard continued IV treatment. Oral therapy TMP-SMX (160/800 mg BD), clindamycin (600 mg TDS) or (for MRSA) linezolid (600 mg BD). IV therapy for MSSA (flu)cloxacillin (2 g QDS) or cefazolin (2 g TDS), for MRSA vancomycin (1 g BD) or daptomycin (6–10 mg/kg OD).	No significant difference in 90-day SAB complications (primary outcome, 4% vs 5% of study population of 165) or death attributable to SAB (secondary outcome, 1% vs 0%) to oral versus IV respectively. Significantly shorter hospital stays were attributable to the EOS group (11 d vs 15 d).	Slow enrolment led to early termination and protocol changes during the trial- though the broadening to include a wider group of those at low-risk of SAB may have made it more applicable to the wider population.
Diego-Yague et al 2023, Sequential oral antibiotic in uncomplicated Staphylococcus aureus bacteremia: a propensity-matched cohort analysis. [18]	Retrospective, single-centre, cohort study, non-randomised	230 uncomplicated participants (112 EOS, 118 IV)	EOS after an median of 7 d. Most commonly co-amoxiclav alone (48%) but also cefadroxil, cefuroxime or cephalexin (all at 1 g TDS) (48%), ciprofloxacin alone (12%) and linezolid (9%) were the most commonly prescribed (other doses not stated).	Significant difference in composite 90-day all-cause mortality and 90-day microbiological failure (primary outcome, 10.7% (11/112) in OST versus 30.5% (36/118) in IVT (P < .001) but this significance was removed once propensity-matched cohort where the primary outcome occurred in 21% (32/154). No higher risk of microbiological relapse, readmission, or mortality.	The IV and EOS groups were propensity-matched, however not completely comparable, as mortality in the EOS cohort was lower than in the IV group. The relatively small sample size and observational nature of the study limits the strength of the conclusions.

Abbreviations: BD, administered twice a day; EOS, early oral switch; IV, intravenous; IVT, IV antibiotic therapy; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin- susceptible Staphylococcus Aureus; OD, administered once a day; OST, oral sequential antibiotic therapy; QDS, administred four times a day; RCT, randomized clinical trial; SAB, S. aureus bacteraemia; SOC, standard of care; TDS, administered three times a day; TMP-SMX, trimethoprim-sulfamethoxazole.