drug is cleared in the first half-life, while the amount of drug that is cleared in the third or
fourth half-life is relatively small. If the antibiotic is given by a continuous infusion, it is
possible to sustain the antibiotic concentration above the desired concentration target, but
without the peaks and troughs that characterize the normal rapid administration.
The strategy has been to give a standard dose of the antibiotic and then begin the
infusion of the drug at an hourly rate that approximates the ordinary total 24-hour
administration under conventional delivery methods (Fig. 4). Some trials have indicated that
distributing the infusion rate over 24 hours permits maintenance of antibiotic concentrations at
target levels, but with a reduction in overall total drug that is given.
Clinical trials that have compared continuous infusion to conventional drug adminis-
tration are summarized in Table 3. The greatest interest in continuous infusion has been in the
b-lactam agents. These are time-dependent agents without an appreciable post-antibiotic
effect, which makes a sustained antibiotic concentration that is above the target threshold a
treatment goal (60). Reviews and meta-analysis of continuous infusion have extolled the
Figure 3 Illustrates the enhanced
serum concentration of antibiotics
that are achieved when the dose is
doubled of a hypothetical drug with a
normal dosing interval of six hours and
aT1/2of 1.5 hours. Doubling the dose
only extends the duration of antibiotic
concentration above the [MIC] target
by one half-life. Point [A] identifies the
peak concentration after doubling the
dose.Figure 4 Illustrates the effects of con-
tinuous infusion and prolonged infusion
upon the serum concentrations of the
theoretical antibiotic model. Continuous
infusion is begun after the initial inter-
mittent full dose has been administered.
The drug concentration flattens out at a
level designed to continuous concentra-
tions above the [MIC] target. The pro-
longed infusion results in an area under
the curve that is similar to the same
dose given normally, but the slower
increase in the peak concentration
results in slower total drug elimination.Antibiotic Kinetics in the Multiple-System Trauma Patient 531