Infective endocarditis (IE) management has shifted in two meaningful ways in recent years: a move toward oral step-down therapy in stabilized patients, and the arrival of new antimicrobials for resistant Gram-positive infection.
Oral step-down therapy
The landmark POET trial established that in patients with left-sided IE who had been stabilized on intravenous antibiotics, switching to oral therapy was non-inferior to continued IV treatment for the composite of mortality, unplanned cardiac surgery, embolic events, or relapse (event rates around 9–12%). This finding, now reflected in guidelines including the 2023 ESC endocarditis guideline, supports partial oral treatment and outpatient management in appropriately selected, stable patients — a significant change from the traditional insistence on prolonged inpatient IV therapy.
Antibiotic selection and new agents
Guidelines favor beta-lactams over vancomycin or daptomycin for methicillin-susceptible Staphylococcus aureus, and ampicillin plus ceftriaxone over aminoglycoside-containing regimens for Enterococcus faecalis — particularly in older patients or those with renal impairment. The notable new agent is ceftobiprole (Zevtera), which was FDA-approved in 2024 for S. aureus bacteremia including right-sided IE (on the strength of the ERADICATE trial, where it was non-inferior to daptomycin) — the first cephalosporin approved for this indication and active against MRSA. Ceftaroline and the long-acting lipoglycopeptides dalbavancin and oritavancin also show promise (dalbavancin is being studied specifically for IE), offering the prospect of simplified, less frequent dosing, though they are not yet standard of care for endocarditis.
Surgery
Early surgery improves outcomes in uncontrolled infection, heart failure from valvular dysfunction, or to prevent central nervous system embolization, and timely referral remains central to management.
Further reading: POET partial oral therapy (Iversen et al., NEJM 2019); native-valve IE (Chambers & Bayer, NEJM 2020); ceftobiprole ERADICATE trial and FDA approval (2024); 2023 ESC infective endocarditis guideline.