Methicillin-resistant Staphylococcus aureus (MRSA) continues to rank among the US Centers for Disease Control and Prevention’s top antimicrobial-resistant threats.1 Capable of causing severe and life-threatening infections, including pneumonia, right-sided endocarditis, surgical site infections, and sepsis, MRSA poses a formidable challenge in both healthcare and community settings. Vulnerable populations, such as those with prolonged hospitalizations, intensive care admissions, renal disease, diabetes, or a history of injection drug use, are particularly at risk.
Additionally, the widespread and increasing use of implantable medical devices, such as pacemakers, orthopedic hardware, and vascular grafts, has introduced new risk pathways for S aureus colonization and infection. Despite advances in management, treatment failures, persistent bacteremia, and relapsing infections remain common. These outcomes reflect both microbial virulence and the limitations of current therapeutic options.
A 2020 study published in The New England Journal of Medicine analyzed data from over 41 million hospitalized patients and identified MRSA as the most frequently identified multidrug resistant (MDR) pathogen in hospitalized patients in the United States. Although national surveillance data show a modest decline in MRSA incidence, bloodstream infections caused by Staphylococcus aureus remain associated with high morbidity and mortality. Crucially, while outcomes have shown modest improvement over time, the 90-day mortality rate following S aureus bacteremia (SAB) approaches 30%. That is, almost 1 in 3 patients do not survive 3 months after they develop SAB.2
While MRSA garners significant attention, methicillin-susceptible Staphylococcus aureus (MSSA) infections are also common and potentially lethal. MSSA accounts for a growing proportion of SAB, and clinicians caring for patients with suspected SAB must therefore utilize empiric coverage strategies that address both MRSA and MSSA.
Given the increasing complexity of SAB cases, there is an urgent need for novel agents and revised treatment frameworks that reflect real-world challenges. Ideal therapies should offer efficacy, safety, predictable pharmacokinetics, and activity against resistant strains, all while addressing the nuances of care in medically complex patients.
The phase 3 ERADICATE trial evaluated ceftobiprole medocaril sodium, the only FDA-approved cephalosporin with activity against both MRSA and MSSA in adult patients with S aureus bloodstream infections. In the modified intention-to-treat (mITT) population, ceftobiprole demonstrated non-inferiority to daptomycin, achieving clinical success rates of 69.8% versus 68.7%, respectively, at 70 days post-randomization. Importantly, both regimens were well tolerated, and the overall incidence of adverse events was comparable. These findings led to FDA approval of ceftobiprole for treatment of SAB, including both MRSA and MSSA – the first such approval in two decades.3
In vitro surveillance data suggest low resistance rates of MRSA and MSSA to ceftobiprole. These findings are particularly encouraging given the limited pipeline of new anti-staphylococcal agents and the growing need for therapies that can reliably address both resistant and susceptible strains in complex clinical scenarios.
What You Need to Know
Staphylococcus aureus bloodstream infections, including both MRSA and MSSA, continue to cause high morbidity and mortality despite advances in care, with a 90-day mortality rate nearing 30%.
The FDA approval of ceftobiprole—the first new agent in two decades active against both MRSA and MSSA—marks an important step forward in managing complex S aureus infections.
Effective management of S aureus bacteremia requires continued development of novel therapies and treatment strategies tailored to increasingly complex patient populations.
Managing SAB requires individualized strategies, an openness to therapeutic innovation, and ongoing evaluation of emerging data. Agents like ceftobiprole are poised to play an increasingly important role, especially in patients with complicated bacteremia, high-risk comorbidities, or previous exposures to anti-staphylococcal therapies.
The burden of SAB is unlikely to diminish without meaningful changes in diagnosis, treatment, and prevention. Incorporating novel agents with robust clinical data may help reduce complications, shorten hospital stays, and improve patient outcomes.
References
1. Methicillin-resistant Staphylococcus aureus (MRSA) Basics. CDC. June 26, 2025. Accessed October 5, 2025. https://www.cdc.gov/mrsa/about/index.html
2.Jernigan JA, Hatfield KM, Wolford H, et al. Multidrug-Resistant Bacterial Infections in U.S. Hospitalized Patients, 2012-2017. N Engl J Med. 2020;382(14):1309-1319. doi:10.1056/NEJMoa1914433
3.Holland TL, Cosgrove SE, Doernberg SB, et al. Ceftobiprole for Treatment of Complicated Staphylococcus aureus Bacteremia. N Engl J Med. 2023;389(15):1390-1401. doi:10.1056/NEJMoa2300220
