Therapeutic Considerations

Treatment of IE often is complicated and difficult. Numerous factors involving the vegetation influence the effectiveness of the antimicrobial agents. The vegetation consists of a fibrin matrix (as discussed earlier) that provides an environment where organisms are relatively free to replicate unimpeded, allowing the microbial density to reach very high concentrations (109-1010 CFU/g). Once the organism density has reached this level, the organisms are virtually in a static growth phase. These factors hinder host defenses, as well as the ability of antimicrobials to produce sufficient kill. This is seen often with ^-lactams and glycopeptides because their effectiveness can be significantly affected by the bacterial inoculum.

^ Selection of an appropriate antimicrobial agent must combine characteristics such as the ability to penetrate into the vegetation, the ability to achieve adequate drug concentrations, and the ability to be minimally affected by high bacterial inoculum in order to achieve adequate kill rates. To accomplish this, antimicrobials typically have to be given parenterally at high doses with an extended treatment course of 4 to 6 weeks (in most cases). Other desirable drug characteristics include bactericidal and synergistic activity.

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