Interference of cephalosporins and cefoxitin with serum creatinine determination

The interference of cephalosporins and cefoxitin with serum creatinine (Crs) determinations was studied. Various concentrations of cephapirin, cefazolin, cefamandole, cephalothin, and cefoxitin were added to serum samples. Apparent creatinine concentrations were measured with the Beckman ASTRA, Technicon SMAC, and DuPont ACA analyzers. Pharmacokinetic models were used to predict serum drug concentrations as a function of time and renal function and to estimate the magnitude of interference in varying situations. The magnitude of the interference was proportional to the concentration of the drug in the sample and additive with baseline concentrations of creatinine in the serum. Negligible interferences occurred with cephapirin, cefazolin, and cefamandole. False elevations (i.e., Crs greater than or equal to 0.2 mg/dl over baseline) were detected with clinically achievable serum concentrations of cephalothin and cefoxitin. For patients with normal renal function (creatinine clearance greater than 50 ml/min), this drug interaction would be negligible from 20 minutes to two hours after drug administration, depending on the assay used. For patients with renal failure, measurable interferences could persist for up to 16 hours after dose administration. The critical concentrations were different for the three procedures and both antibiotics. The degree of interference varies with the assay procedure used, the serum concentration of the drug, and the patient's renal function. To minimize drug interference, blood samples for serum creatinine determinations should be drawn at the time of minimum drug concentration.