Oral antibiotics for infective endocarditis: a clinical review

Current guidelines for management of infective endocarditis (IE) advise 4-6 weeks of IV antibiotics. This is based on historical data from animal models, which set a precedent for high peak serum antimicrobial levels, thought to be only achievable with IV therapy. However, there has been increasing recent interest in oral antibiotics as an alternative to prolonged parenteral therapy, not limited to treatment of IE. This review examines the theory behind parenteral antibiotic administration with reference to the MICs of relevant pathogens. By comparing published serum antimicrobial levels after oral and IV administration we suggest that safe levels of commonly used antibiotics can be achieved orally. We have then reviewed the literature to date on oral antibiotics for IE. The largest randomized controlled trial (RCT) in this area, the POET trial, concluded that oral therapy was non-inferior to prolonged IV therapy in stable patients with left-sided IE. Additionally, there have been two smaller RCTs published, as well as a number of observational studies over the last 50 years, utilizing a variety of different patient groups, methods and treatment strategies. This body of evidence gives weight to a potential shift in practice towards oral therapy, primarily as a step-down treatment. We conclude that pharmacological data offer theoretical reassurance for the safety of oral therapy. This is coupled with a growing evidence base for non-inferiority of oral antimicrobials compared with prolonged parenteral therapy in practice.