Crossover assessment of serum bactericidal activity and pharmacokinetics of five broad-spectrum cephalosporins in the elderly

Abstract

To better define the pharmacokinetics and serum bactericidal activity (SBA) of the expanded-spectrum cephalosporins in the elderly, we administered single 2-g intravenous infusions of cefoperazone, cefotaxime, ceftriaxone, ceftazidime, and ceftizoxime to six healthy volunteers over the age of 65 years. Serum was collected over 24 h, and concentrations were determined by high-performance liquid chromatography; pharmacokinetic parameters were determined for each drug. SBA was measured against representative strains of Staphylococcus aureus, Escherichia coli, KiebsieUa pneumoniae, Enterobacter aerogenes, and Pseudomonas aeruginosa. All agents tested had excellent SBAs against E. coil and K. pneumoniae, often for a longer duration than would be expected on the basis of conventional dosing regimens. Ceftazidime had the greatest SBA against E. aerogenes and was the only agent with a substantial SBA against P. aeruginosa. Although ceftizoxime had the greatest SBA against S. aureus, none of these cephalosporins had substantial antistaphylococcal SBAs. Pharmacokinetic analysis revealed that cefoperazone and ceftriaxone had markedly different concentration-time profiles in the elderly volunteers than would have been expected on the basis of existing data from younger volunteers. For older patients, dosing guidelines for these two agents may need to be altered.The broad-spectrum cephalosporins cefoperazone, cefotaxime, ceftriaxone, ceftazidime, and ceftizoxime are administered commonly to elderly patients. Although the pharmacokinetics of these cephalosporins have been well studied (1), there have been no crossover pharmacokinetic trials in the elderly.Conventional in vitro susceptibility tests measure only inhibitory antimicrobial activity under standard laboratory conditions. An alternative to conventional susceptibility tests, the serum bactericidal test (SBT), may provide a more meaningful measure of the potential usefulness of antimicrobial agents (7,22,43,47,(52)(53)(54). The SBT takes into consideration the achievable concentration of the antimicrobial agent in serum as well as its inherent antibacterial activity, and guidelines for a standard test method have been published recently (35). In studies in which serum bactericidal testing has been used in young volunteers, differences in the broad-spectrum cephalosporins have been shown, including pharmacokinetics, in vitro activity, and serum bactericidal activity (SBA) (3,4,15,17,18,23,38,49,50). Although elderly individuals may exhibit altered metabolism and pharmacokinetics of these antimicrobial agents (1,19,21,24,26,27,(31)(32)(33)42), no studies of SBA have been done in this population. Therefore, we administered single 2-g doses of cefoperazone, cefotaxime, ceftriaxone, ceftazidime, and ceftizoxime to six healthy elderly volunteers and studied both the pharmacokinetics and SBAs of these agents.* Corresponding author. MATERIALS AND METHODSStudy subjects. Six healthy elderly volunteers (three males, three females) participated in the study. They had the following...

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