Oral Therapy for Infective Endocarditis: Where Do We Stand?

Standard therapy for infective endocarditis (IE) usually requires 4-6 weeks of intravenous (IV) antibiotics, ensuring sustained bactericidal concentrations, yet resulting in prolonged hospitalization and increased cost of care. These challenges have driven interest in oral antibiotic therapy (OAT) as a step-down strategy for selected, clinically stable patients. This review summarizes the clinical evidence and pharmacokinetic and pharmacodynamic (PK/PD) rationale and practical considerations supporting step-down OAT in IE. Antibiotics such as amoxicillin, fluoroquinolones, linezolid, and rifampicin have high bioavailability and maintain effective serum and tissue concentrations, and can be used as a safe transition from IV to oral therapy. The pivotal POET randomized controlled trial (RCT) demonstrated noninferiority of OAT compared with continued IV therapy in stable patients with left-sided IE caused by <i>Streptococcus</i> spp., <i>Enterococcus faecalis</i>, methicillin-susceptible <i>Staphylococcus aureus</i>, or coagulase-negative staphylococci. Further real-world studies and meta-analyses confirmed comparable efficacy and safety, with reduced catheter-related complications and shorter hospitalization length for patients receiving OAT. The latest European Society of Cardiology (ESC) guidelines have incorporated OAT regimens derived from the POET protocol for stable patients meeting specific criteria, while the American Heart Association guidelines have not yet been revised. Many areas remain uncertain, such as the optimal timing of transition to oral therapy; the ideal antibiotic combinations and dosing; and the applicability to complex cases such as methicillin-resistant <i>S. aureus</i> (MRSA), Gram-negative, or pediatric infections. Overall, clinical evidence supports OAT as a safe and effective alternative to prolonged IV therapy in selected patients with IE, highlighting a major step toward more individualized, patient-centered management.