The most important pharmacodynamic parameter for beta-lactam antibiotics
          has been shown to be the time above the MIC, which is used as an argument
          to administer beta-lactam antibiotics by continuous infusion. Studies in
          vitro and in laboratory animals comparing efficacy of continuous an

Mouton, J.W. (Johan)

Vinks, A.A.

The most important pharmacodynamic parameter for beta-lactam antibiotics
          has been shown to be the time above the MIC, which is used as an argument
          to administer beta-lactam antibiotics by continuous infusion. Studies in
          vitro and in laboratory animals comparing efficacy of continuous and
          intermittent infusion of beta-lactam antibiotics generally show continuous
          infusion to be more efficacious. While comparative trials in humans are
          scarce and a significant difference was only found in subgroup analysis in
          one study, several case-reports support the use of continuous infusion.
          Arguments in favour and against continuous infusion are discussed.
          Although dose-ranging studies have not yet been performed in humans, the
          results from in-vitro and in-vivo experiments indicate that 4 x MIC for
          the infecting bacterium would be the target concentration. Pharmacokinetic
          studies which have been performed in humans during continuous infusion
          show that serum concentrations can be predicted from total clearance or,
          using population pharmacokinetic modelling, the elimination rate constant
          as obtained during intermittent infusion. A nomogram is presented which
          allows calculation of the daily dose to obtain the target steady state
          blood concentrations suggested by the susceptibility of the infecting
          bacterium, usually 4 x MIC. For bacteria with a low MIC, the daily dose
          may be substantially lower than that used in conventional dosing regimens,
          while in infections which are difficult to treat as a result of more
          resistant bacteria, continuous infusion may be more effective than an
          equivalent bolus dose

Is continuous infusion of beta-lactam antibiotics worthwhile?--efficacy and pharmacokinetic considerations

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