Rational prescribing of extended-spectrum penicillin beta-lactamase inhibitor combinations: focus on ticarcillin/clavulanic acid. 1998

M D Reed
Division of Pediatric Pharmacology and Critical Care, Rainbow Babies and Children's Hospital, Cleveland, OH 44106, USA.

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. METHODS 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. RESULTS 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.

UI MeSH Term Description Entries
D011307 Drug Prescriptions Directions written for the obtaining and use of DRUGS. Drug Prescribing,Drug Prescription,Drug Prescribings,Prescribing, Drug,Prescribings, Drug
D002969 Clavulanic Acids Acids, salts, and derivatives of clavulanic acid (C8H9O5N). They consist of those beta-lactam compounds that differ from penicillin in having the sulfur of the thiazolidine ring replaced by an oxygen. They have limited antibacterial action, but block bacterial beta-lactamase irreversibly, so that similar antibiotics are not broken down by the bacterial enzymes and therefore can exert their antibacterial effects. Acids, Clavulanic
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000367 Age Factors Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time. Age Reporting,Age Factor,Factor, Age,Factors, Age
D013982 Ticarcillin An antibiotic derived from penicillin similar to CARBENICILLIN in action. BRL-2288,Tarcil,Ticar,Ticarcillin Disodium,Ticarpen,Ticillin,BRL 2288,BRL2288,Disodium, Ticarcillin
D065093 beta-Lactamase Inhibitors Endogenous substances and drugs that inhibit or block the activity of BETA-LACTAMASES. beta Lactamase Inhibitor,beta Lactamase Inhibitors,beta-Lactamase Inhibitor,beta Lactamase Antagonists,Antagonists, beta Lactamase,Inhibitor, beta Lactamase,Inhibitor, beta-Lactamase,Inhibitors, beta Lactamase,Inhibitors, beta-Lactamase,Lactamase Antagonists, beta,Lactamase Inhibitor, beta,Lactamase Inhibitors, beta

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