Partial Oral Antibiotic Therapy in Infective Endocarditis: Evidence, Patient Selection, and Practical Implementation

Infective endocarditis (IE) is a life-threatening infection traditionally treated with 4-6 weeks of intravenous (IV) antibiotics. Emerging data, including the Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis trial and recent meta-analyses, suggest that selected clinically stable patients can safely transition early to oral regimens, but practical guidance on implementation is limited. We conducted a comprehensive narrative review of randomized trials, observational studies, ongoing clinical trials, meta-analyses, and contemporary guidelines addressing partial oral antibiotic therapy in adult IE. Evidence consistently shows that after at least 10 days of effective IV treatment, patients who are afebrile, hemodynamically stable, have negative blood cultures, and no uncontrolled infection on imaging can be transitioned to dual oral regimens with high bioavailability and pathogen-directed activity. In this population, oral step-down therapy yields similar rates of death, relapse, embolic events, and unplanned cardiac surgery compared with prolonged IV therapy, while substantially reducing hospital length of stay and line-related complications. Data in people who inject drugs, those with multidrug-resistant pathogens, or severe heart failure remain limited, and robust pharmacokinetic validation of some oral β-lactam-based combinations is still needed. Overall, partial oral antibiotic therapy represents a safe, evidence-based, and stewardship-aligned strategy for many patients with left-sided native or prosthetic valve IE when applied within structured protocols and strict selection criteria.