Abstract

Background:
Methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSIs) are a major global cause of morbidity and mortality. Although standard-of-care (SOC) treatments, such as oxacillin, nafcillin, and cefazolin, are effective, they require frequent dosing and prolonged hospital stays. Ceftriaxone, with its once-daily dosing, offers a potentially more convenient alternative. However, its efficacy and safety in treating MSSA-BSIs remain unclear.

Aim:
This systematic review and meta-analysis aimed to compare the efficacy and safety of ceftriaxone versus standard therapy across diverse clinical settings in adult patients with MSSA-BSIs.

Methods:
A comprehensive literature search was conducted across PubMed, Embase, and Scopus up to March 15, 2024. Randomized controlled trials and observational studies comparing ceftriaxone with SOC for MSSA-BSI were included. The primary outcomes were clinical cure, microbiological cure, and mortality. Secondary outcomes included adverse drug reactions (ADRs), hospital readmissions, treatment failure, emergency department visits, and length of hospital stay. Data analysis was performed using comprehensive meta-analysis software.

Results:
Nineteen studies were included with varied designs and clinical settings. Ceftriaxone showed no statistically significant difference in clinical cure [odds ratio (OR) 0.74, p = 0.391], microbiological cure (OR 0.94, p = 0.844), or 90-day mortality (OR 1.29, p = 0.498) compared with SOC. However, 30-day mortality was higher with ceftriaxone (OR 1.91, p = 0.004). Ceftriaxone demonstrated a nonsignificant trend toward fewer ADRs and lower hospital readmission rates.

Conclusion:
Ceftriaxone may offer comparable efficacy and improved convenience in the treatment of MSSA-BSI for selected patients, particularly in outpatient settings. However, the increased risk of 30-day mortality highlights the need for caution in critically ill populations. Further high-quality randomized trials are needed to clarify the role of ceftriaxone in MSSA-BSI management.

Key words: Ceftriaxone; MSSA; Bacteremia; Bloodstream infection; Antimicrobial therapy; Meta-analysis.