Rational Prescribing of Extended-Spectrum Penicillin β-Lactamase Inhibitor Combinations: Focus on Ticarcillin/Clavulanic Acid

Abstract

OBJECTIVE To provide an overview of the clinical pharmacokinetics and pharmacodynamics of ticarcillin/clavulanic acid and to reassess traditional dosage recommendations based on contemporary pharmacokinetic and pharmacodynamic principles. DATA SOURCES Published ticarcillin and clavulanic acid pharmacokinetic data derived from infants and children combined with data obtained from a rigorous, dose-escalation study performed in 12 healthy adults. Pharmacodynamic correlates were derived from published in vitro susceptibility data for the combination drug ticarcillin/clavulanic acid. DATA SYNTHESIS: Limited differences were observed in the pharmacokinetic disposition profiles between ticarcillin and clavulanic acid and relative to subject age. Integration of these data with defined pathogen minimum inhibitory concentrations underscores the appropriateness of an extended dosing interval (e.g., q8h to q12h) for many infections and demonstrates the probable therapeutic interchangeability of the following three intravenous dosing regimens: 3.1 g every 6 hours, 75 mg/kg every 8 hours, and 100 mg/kg every 12 hours of a 30:1 ticarcillin/clavulanic acid combination. CONCLUSIONS Integration of pharmacokinetic and pharmacodynamic data is an appropriate means to assess/reassess dosing recommendations for antimicrobial agents. Initial ticarcillin/ clavulanic acid dose recommendations did not account for known dynamic interactions for this combination antibiotic. Pharmacokinetic data in infants, children, and adults support a less frequent dosing interval (q8h to q12h) for the treatment of infections arising outside the central nervous system.