Pharmacokinetic and economic evaluation of piperacillin/tazobactam administered as either continuous or intermittent infusion with once-daily gentamicin

With increasing use of once-daily aminoglycoside dosing and renewed interest in continuous infusions of β-lactam agents, there is a need to study the interaction between aminoglycosides and penicillins as it relates to these nontraditional dosing regimens. Twelve healthy volunteers each received a continuous (500 mg/h based on the piperacillin component) and an intermittent (4.5 g q6h) infusion of piperacillin/tazobactam with and without a single high dose of gentamicin (7 mg/kg). The effect of gentamicin on the serum concentration of the piperacillin component was measured for each dosing regimen. Continuous infusion of piperacillin/tazobactam resulted in a mean steady-state piperacillin concentration of 28.0 μg/mL. The piperacillin concentration, after the simultaneous 1-hour infusion of gentamicin, was statistically unchanged at 29.7 μg/mL. After intermittent administration of piperacillin/tazobactam, piperacillin's maximum concentration, half-life, and area under the concentration-time curve were 232 μg/mL, 0.81 hours, and 354 μg-h/mL, respectively. These pharmacokinetic values were also statistically unchanged when a concomitant dose of gentamicin was given. Gentamicin concentrations were not affected by either dosing method of piperacillin/tazobactam. Administering oncedaily gentamicin to volunteers receiving piperacillin/tazobactam by continuous infusion or by intermittent dosing does not alter the pharmacokinetic parameters of piperacillin or gentamicin. Compared with intermittent infusion, continuous infusion results in lower costs, mainly from a reduction in labor and supply costs.