Table 1. Urinary Creatinine and Creatinine Clearance Values in Four Patients Receiving Cephalosporins

of cephalothin immediately post-infusion were 250 mg/L after a 2-g infusion, 100 mg/L after a 1-g infusion. The increase in apparent plasma creatinine declined more slowly with time than did cefoxitin. This is likely due to the higher concentrations of creatinine in plasma and to the additional interference by desacetylcephalothin. Cefoxitin is essentially unmetabolized. Two 24-h urine specimens, one collected during steady state and the other at least five biological half-lives after the drug was discontinued, were collected from each of two patients receiving cefoxitin and two receiving cephalothin. Urinary creatinine concentrations and their differences were calculated, as well as the creatinine clearances and their differences (Table 1). We calculated creatinine clearances when the patients were on cephalosporin, using plasma creatinine values obtained when cephalosporin concentrations were lowest. In three patients, there were increases in apparent urinary creatinine, and the average increase in clearance was 18 mL/min. Because cephalothin and Cefoxitin are eliminated primarily by renal tubular secretion, whereas creatinine is lost mainly by glomerular filtration, the status of a patient’s glomerular function relative to tubular function may affect the degree of interference with respect to urine. This may explain the failure of one patient to demonstrate such interference. Other factors could be an incomplete 24-h-urine collection or a change in renal function on the collection day. Overall, creatinine clearance is not a clinically reliable index of glomerular filtration for patients being treated with cephalosporins, because the values for apparent plasma creatinine vary during a dosing interval as cephalosporin concentrations fluctuate. If the clearance is calculated with the plasma creatinine value obtained when cephalosporin values are minimal, false increases in creatinine clearance are observed. This confirms the results of Durham et al. with cefoxitin (4), but contradicts those of Rankin et al. with cephalothin (3). The latter authors may have minimized increases in the creatinine clearance by fortuitously using plasma creatinine values at the highest cephalosporin concentrations. In summary, cephalosporins falsely increase apparent creatinine in plasma and in urine, both in vitro and in vivo when a direct Jaff#{233} reaction is used. The significance of the in vivo interference depends on the clinician’s interpretation of results; therefore, to promote awareness and management of potential interferences, we developed the following guidelines for interpretation of plasma creatinine and creatinine clearance results: 1. In patients receiving cephalothin and cefoxitin, use caution in interpreting creatinine values from patients on maximal doses or patients with renal dysfunction. 2. Draw blood for the measurement of creatinine values when cephalosporin concentrations are low, to minimize interference. 3. Verify creatinine clearance calculations with an estimate from a nomogram such as that of Siersback-Nielson. The plasma creatinine concentration measured when cephalosporin is lowest should be used. 4. When doses of drugs are calculated on the basis of a creatinine clearance value obtained during concomitant cephalosporin administration, monitor the serum drug concentrations where possible.