Medical treatment of infective endocarditis: general principles.

The main objective of medical treatment of infective endocarditis is to sterilize the vegetative lesions characteristic of the disease. The general principles of treatment are: (1) identification of the causative organism; (2) in vitro determination of its susceptibility, and (3) the choice of a bactericidal treatment. In vitro susceptibility, the minimum inhibitory concentration (MIC)/minimum bactericidal concentration (MBC) rate, the level of aminoglycoside resistance and in vitro synergy testing are determined according to the organism. Bactericidal therapy requires a combination of antimicrobials with synergistic activity, generally a cell-wall-active agent and an aminoglycoside. Treatment must be instituted parenterally, to ensure complete bioavailability, high serum concentrations and good penetration into the vegetations. The mode of administration depends on the organism, the serum-half-life and the mode of antimicrobial effect whether time or concentration-dependent, and the post-antibiotic effect (PAE). Cell-wall-active antibiotics (beta-lactams and glycopeptides) with a time-dependent activity require concentrations above MIC for as long as possible between administrations, mainly if there is no PAE; conversely, aminoglycosides or fluoroquinolones with a concentration-dependent activity must be used to obtain a peak-concentration five to ten times the MIC. Therapy must be monitored rigorously. The clinical relevance of serum bactericidal titre is poor owing to lack of standardization and its poor predictive value of failure. The duration of therapy must be sufficient (4-6 weeks) to prevent failure or relapse.