Pharmacokinetics and pharmacoeconomic evaluation of ticarcillin-clavulanate administered as either continuous or intermittent infusion with once-daily gentamicin

Although ticarcillin-clavulanate, a p-lactam and p-lactamase inhibitor comb ination, is traditionally administered intermittently, there is no reason w hy it cannot be given by continuous infusion. In severe nosocomial infectio ns involving unusual Enterobacteriaceae, Pseudomonas aeruginosa, or Enteroc occus species, this agent is often combined with a once-daily dose of genta micin or tobramycin (7 mg/kg) for synergy. However, observations from case reports and static in vitro studies have documented the potential for the i nactivation of these two antibiotics when given concomitantly. This study w as undertaken to determine the extent of an in vivo inactivation of ticarci llin (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 stud y, during which no statistically significant differences were noted in the area under the curve (AUC), maximum concentration, or half life of three ti carcillin-clavulanate doses given in the presence of gentamicin. In the nin e volunteers who received a continuous infusion of ticarcillin-clavulanate, a statistically significant (P < .008) reduction in ticarcillin concentrat ions (70 vs. 55 mu g/mL) were observed after the administration of gentamic in. The AUC of gentamicin was unchanged whether the ticarcillin-clavulanate were administered by continuous or intermittent infusion. Although the ina ctivation of ticarcillin resulted in lowered concentrations during continuo us infusion, this reduction should be of minimal, if any, relevance clinica lly because the concentrations exceeded the MIC for organisms that test sus ceptible to this drug. Assuming no difference in clinical outcomes whether ticarcillin-clavulanate is given by continuous or intermittent infusion, th e continuous infusion method becomes a very attractive option, owing to the major economic gains obtained by this dosing method, mainly from the reduc tion in labor and supply costs.