RATIONAL PRESCRIBING OF EXTENDED-SPECTRUM PENICILLIN BETA-LACTAMASE INHIBITOR COMBINATIONS - FOCUS ON TICARCILLIN CLAVULANIC ACID/

OBJECTIVE: TO provide an overview of the clinical pharmacokinetics and pharmacodynamics of ticarcillin/clavulanic acid and to reassess tradi tional dosage recommendations based on contemporary pharmacokinetic an d 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 pe rformed in 12 healthy adults. Pharmacodynamic correlates were derived from published in vitro susceptibility data for the combination drug t icarcillin/clavulanic acid. DATA SYNTHESIS: Limited differences were o bserved in the pharmacokinetic disposition profiles between ticarcilli n and clavulanic acid and relative to subject age. Integration of thes e data with defined pathogen minimum inhibitory concentrations undersc ores the appropriateness of an extended dosing interval (e.g., q8h to q12h) for many infections and demonstrates the probable therapeutic in terchangeability 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 hou rs of a 30:1 ticarcillin/clavulanic acid combination. CONCLUSIONS: Int egration of pharmacokinetic and pharmacodynamic data is an appropriate means to assess/reassess dosing recommendations for antimicrobial age nts. 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 infection s arising outside the central nervous system.