Int J Antimicrob Agents. 2021 Nov 25:106486. doi: 10.1016/j.ijantimicag.2021.106486. Online ahead of print.
Optimal therapy for methicillin-susceptible Staphylococcus aureus (MSSA) infections is unclear. The current standard of care consists of anti-staphylococcal antibiotics (ASA), such as nafcillin, oxacillin, and cefazolin. Ceftriaxone has been evaluated due to its advantage as a once-daily outpatient regimen. However, questions remain regarding efficacy compared to ASA. We aimed to conduct a review and synthesis of available literature for outcomes of patients treated with ceftriaxone or ASA for MSSA infections. We searched Cochrane Central Register of Controlled Trials, Embase, Ovid MEDLINE, Scopus, and Web of Science from 1990 to June 2021. Risk of bias for cohort studies was assessed by the Newcastle-Ottawa quality scale. We pooled risk ratios (RR) using the DerSimonian-Laird random effects model for outcomes of those who received ceftriaxone compared to ASA. 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 alteration of therapy [RR 0.49 (95% confidence interval [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 ASA 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].