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, Klebsiella pneumoniae, Enterobacter aerogenes, and Pseudomonas aeruginosa. All agents tested had excellent SBAs against E. coli 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.