Pharmacokinetics and Pharmacoeconomic Evaluation of Ticarcillin-Clavulanate Administered as Either Continuous or Intermittent Infusion with Once-Daily Gentamicin

Abstract

Although ticarcillin-clavulanate, a β-lactam and β-lactamase inhibitor combination, is traditionally administered intermittently, there is no reason why it cannot be given by continuous infusion. In severe nosocomial infections involving unusual Enterobacteriaceae, Pseudomonas aeruginosa, or Enterococcus species, this agent is often combined with a once-daily dose of gentamicin or tobramycin (7 mg/kg) for synergy. However, observations from case reports and static in vitro studies have documented the potential for the inactivation of these two antibiotics when given concomitantly. This study was undertaken to determine the extent of an in vivo inactivation of ticarcillin (given as ticarcillin-clavulanate) administered as either intermittent or continuous infusion, with and without gentamicin, in healthy volunteers. Eleven volunteers completed the intermittent infusion portion of the study, during which no statistically significant differences were noted in the area under the curve (AUC), maximum concentration, or half-life of three ticarcillin-clavulanate doses given in the presence of gentamicin. In the nine volunteers who received a continuous infusion of ticarcillin-clavulanate, a statistically significant (P< .008) reduction in ticarcillin concentrations (70 vs. 55 μg/mL) were observed after the administration of gentamicin. The AUC of gentamicin was unchanged whether the ticarcillin-clavulanate were administered by continuous or intermittent infusion. Although the inactivation of ticarcillin resulted in lowered concentrations during continuous infusion, this reduction should be of minimal, if any, relevance clinically because the concentrations exceeded the MIC for organisms that test susceptible to this drug. Assuming no difference in clinical outcomes whether ticarcillinclavulanate is given by continuous or intermittent infusion, the continuous infusion method becomes a very attractive option, owing to the major economic gains obtained by this dosing method, mainly from the reduction in labor and supply costs.