Ceftazidime in the elderly: appropriateness of twice-daily dosing

Abstract

The disposition of drugs in the elderly is particularly relevant with antiinfectives, because this population has an increased risk of infections. Renal function deteriorates with age, yet dosage guidelines for antibiotics that allow for this reduction remain to be established. Ceftazidime, a cephalosporin with enhanced antipseudomonal activity that is eliminated primarily by glomerular filtration, has been evaluated in the elderly. Herein, we review ceftazidime's pharmacokinetic profile and dosing considerations in this population. Several aspects of renal function deteriorate with the normal aging process, including a decreased glomerular filtration rate (GFR). Using serum creatinine concentrations as an estimate of the GFR in the elderly is unreliable; a more reliable way of estimating GFR is the use of inulin or 51Cr-editic acid clearance or calculation from formulas or nomograms based on age, weight, sex, and serum creatinine. From pharmacokinetic studies it was found that the elderly individual without renal disease generally has an increased elimination half-life and decreased clearance of ceftazidime compared with a young person. A positive correlation (r = 0.7-0.95) was shown between ceftazidime clearance and GFR, suggesting that estimates of GFR may be used to determine the ceftazidime dose. In several studies, the trough (after 12 hours) ceftazidime serum concentration exceeded by several fold its minimum inhibitory concentration required to inhibit 90% of organisms for most commonly encountered organisms; efficacy and safety were also confirmed with an every-12-hour regimen. A twice-daily dosage regimen for ceftazidime in elderly patients with normal renal function should be considered based on age-related decreases in renal function and drug elimination.