LAUSR

(1) Background: Ceftriaxone is a potential alternative for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSIs) in acute care and outpatient parenteral antimicrobial therapy (OPAT) settings. We evaluated the effectiveness and safety of ceftriaxone for the treatment of MSSA BSIs. (2) Method: We searched PubMed, Embase, and Cochrane Library from their inception to October 30th 2021. Our outcomes included clinical cure, microbiological cure, 30- and 90-day mortality, 90-day hospital readmission, and adverse drug reactions (ADRs). We compared ceftriaxone against standard of care (SOC) therapy. We used the random-effects model for the meta-analysis, and our estimated effects were reported as odds ratios (ORs) with 95% confidence intervals (CI). (3) Results: Twelve retrospective cohort studies were included, comprising 1037 patients in the ceftriaxone arms and 2088 patients in the SOC arms. The clinical cure rate of the ceftriaxone regimen was not statistically different from SOC: OR 0.65 (95% CI: 0.29–1.45). Ceftriaxone was also not statistically different from SOC in microbiological cure: OR 1.48 (95% CI: 0.29–7.51); 30-day mortality: OR 0.79 (95% CI: 0.14–4.65); 90-day mortality: OR 0.82 (95% CI: 0.38–1.80); 90-day hospital readmission: OR 1.20 (95% CI: 0.92–1.56); and ADRs: OR 0.92 (95% CI: 0.39–2.18). (4) Conclusion: Ceftriaxone could provide an alternative for the treatment of MSSA BSIs in acute care and OPAT settings (except in patients whose BSIs were due to infective endocarditis).