Effectiveness and Safety of Ceftriaxone Compared to Standard of Care for Treatment of Bloodstream Infections Due to Methicillin-Susceptible Staphylococcus aureus: A Systematic Review and Meta-Analysis

Abstract

(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).

Heartbreaking Decisions: The Dogma and Uncertainties of Antimicrobial Therapy in Infective Endocarditis

“…A subgroup analysis of IE treated with ceftriaxone ( n = 42) compared to cefazolin or oxacillin ( n = 41) demonstrated ceftriaxone to be associated with a numerically higher rate of both the primary composite outcome (25.6% vs. 10%, p = 0.17) and 90-day all-cause mortality (14.3% vs. 2.4%, p = 0.11) [ 23 ]. Most recently, a systematic review and meta-analysis evaluated the use of ceftriaxone ( n = 1037) compared to standard of care (SOC) ( n = 2088) therapies (i.e., ASPs and cefazolin) in MSSA bacteremia [ 24 ]. It did not identify a statistically significant difference between groups for clinical cure, microbiologic cure, 30-day/90-day mortality, 90-day hospital readmission, or adverse drug reaction (ADR) occurrence.…”

“…Only 7 of the 12 studies included enrolled patients with IE (11.5% of total cohort with IE), and the treatment distribution was routinely skewed toward the SOC arm. As a result, the authors concluded that the findings could not be extrapolated to IE given the underrepresentation in the population [ 24 ].…”

Rational Use of Ceftriaxone in Necrotizing Fasciitis and Mortality Associated with Bloodstream Infection and Hemorrhagic Bullous Lesions

“…Ceftriaxone is one of the commonly utilized antibiotics due to its commendable antibacterial efficacy and excellent activity against many Gram-negative and most Gram-positive bacteria in patients with bacteremia, pneumonia, a urinary tract infection, necrotizing soft tissue infection, bone and joint infections, and bacterial meningitis [ 29 , 30 , 31 , 32 , 33 ]. Although the increasing prevalence of ceftriaxone-resistant Gram-negative pathogens has been reported as a concerning issue in critically ill patients, ceftriaxone is still recommended to be effective for blood stream infections and various community-acquired infections due to its excellent safety profile in many literatures [ 24 , 25 , 26 , 34 , 35 , 36 , 37 ]. Our study demonstrated that 89.2% of Gram-positive and Gram-negative pathogens was susceptible to ceftriaxone.…”

Update on Staphylococcus aureus bacteraemia

“…Previous cohort studies of patients with MS-SAB had highlighted worse outcomes with ceftriaxone when compared with cefazolin and/or cloxacillin [29,30]. Two meta-analyses were recently reported [31,32], and concluded to similar mortality outcomes when comparing ceftriaxone with SOC for MS-SAB or MSSA infections. All included studies were retrospective observational, which carries a high risk of bias by indication and residual confounding.…”