Ceftriaxone Versus Antistaphylococcal Antibiotics for Definitive Treatment of Methicillin-Susceptible Staphylococcus Aureus Infections: a Systematic Review and Meta-Analysis.

Optimal therapy for methicillin-susceptible Staphylococcus aureus (MSSA) infections is unclear. Current standard of care consists of antistaphylococcal antibiotics (ASAs) such as nafcillin, oxacillin and cefazolin. Ceftriaxone has been evaluated due to its advantage as a once-daily outpatient regimen. However, questions remain regarding its efficacy compared with ASAs. We aimed to conduct a review and synthesis of available literature for outcomes of patients treated with ceftriaxone or ASAs for MSSA infections. We searched Cochrane Central Register of Controlled Trials, Embase Ovid, MEDLINE Ovid, Scopus and Web of Science (1990 to June 2021). Risk of bias for cohort studies was assessed by the Newcastle-Ottawa scale. We pooled risk ratios (RRs) using the DerSimonian-Laird random-effects model for outcomes of those receiving ceftriaxone versus ASAs. Heterogeneity was assessed by the I2 index. From 459 identified studies, 7 were included in the quantitative synthesis totalling 1640 patients. Definitive therapy with ceftriaxone was associated with a lower risk of toxicity requiring therapy alteration (RR 0.49, 95% CI 0.27-0.88; I2 = 0%). There was no difference in terms of 90-day all-cause mortality (RR 0.93, 95% CI 0.46-1.88; I2 = 9%), hospital readmission (RR 0.96, 95% CI 0.57-1.64; I2 = 0%) or infection recurrence (RR 1.04, 95% CI 0.63-1.72; I2 =0%). Current evidence suggests there is no difference in efficacy between ceftriaxone and ASAs for MSSA infection, with a lower risk of toxicity with ceftriaxone. Within the limitations of available retrospective studies, ceftriaxone is a consideration for definitive therapy of MSSA infection. [Trial registration: PROSPERO ID: CRD42021259086].