Combination antibiotic therapy: comparison of constant infusion and intermittent bolus dosing in an experimental animal model.

To determine the effect of the mode of administration on antibiotic efficacy, 300 neutropenic rats were infected intraperitoneally with an LD-70 inoculum of Pseudomonas aeruginosa and treated with synergistic combinations of amikacin and ticarcillin by intermittent or constant infusion technique. The treatment regimens were designed to provide the same peak serum concentrations that would be observed in humans receiving these drugs. Drug administration over the 24-h period was controlled to ensure that intermittent and constant infusion techniques achieved the same area under the serum concentration/time curves. Based on cumulative mortality at 96 h and viable bacterial cell counts at the site of inoculation constant infusion of both antibiotics produced the best therapeutic results.