Pulse dosing versus continuous infusion of antibiotics. Pharmacokinetic-pharmacodynamic considerations.
The issue of whether it is better to administer antibiotics as an intermittent bolus dose or a continuous intravenous infusion has been debated for several decades. This paper reviews the extensive literature on the topic, considering both the pharmacokinetic and pharmacodynamic aspects of antibacterials as well as experimental results from studies conducted in vitro, in animals and in humans. It is evident from reviewing the literature that neither mode of administration is clearly superior to the other. The decision regarding the mode of administration must take into account the antibiotic being used, the bacteria, the patient and the infection, as well as the pharmacokinetics of the particular drug in the individual patient. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) are useful indicators of the relative in vitro effectiveness of antibiotics, but it is not clear what relevance these parameters have to the desired antibiotic concentrations in vivo. Furthermore, questions of serum vs tissue fluid concentrations, peak concentrations vs AUC, and free vs total concentration are all important issues to consider in assessing the optimal mode of administration. The importance of newer indices such as the post-antibiotic effect are now beginning to be recognised. A number of scientists are actively engaged in developing a system to identify the most appropriate mode of administration based upon the integration of an antibiotic's pharmacodynamics and pharmacokinetics. Within the next few years we anticipate that appropriate guidelines should have been developed to aid the optimisation of parenteral administration, at least for some antibiotics.