Cefepime versus cefpirome: the importance of creatinine clearance

Standard dosage recommendations for beta-lactam antibiotics can result in very low drug levels in intensive care (IC) patients without renal dysfunction. We compared the pharmacokinetics of two fourth-generation cephalosporins, cefepime and cefpirome, and examined the relationship of drug clearance (CL) to creatinine clearance (CL(CR)). Two separate but similar pharmacokinetic studies (which used 2 g twice daily for each antibiotic) were conducted. Blood was sampled after an initial and a subsequent antibiotic dose. Drug plasma concentrations were measured, and pharmacokinetic analyses were conducted and compared. The pharmacokinetics of cefepime and cefpirome are similar in IC patients. Any differences in drug CL can largely be attributed to differences in CL(CR). Despite normal plasma creatinine concentrations, 54% of patients' antibiotic concentrations were less than the minimum inhibitory concentration (MIC) (4 mg/L) for >20% of the dosing interval. Thirty-four percent of patients had CL(CR) >144 mL/min (20% higher than the expected maximum of 120 mL/min). Only CL(CR) was an independent predictor of antibiotic CL. Time above MIC was predicted only by CL(CR). Some IC patients have a very large CL(CR), which results in very low levels of studied antibiotics. Either shortening the dosage interval or using continuous infusions would prevent low levels and keep troughs above the MIC for longer periods. In view of the lack of bedside measurement of cephalosporin levels, we suggest that more frequent use be made of CL(CR) to allow prediction of small concentrations clinically.

Some intensive care patients have very large creatinine clearances that result in very low levels of fourth-generation cephalosporins. Serum levels of these antibiotics need to be maintained (time > minimum inhibitory concentration is important). Because routine measurements of cephalosporin levels are generally unavailable, we suggest that more frequent use be made of creatinine clearances to allow prediction of low levels and, hence, alterations in dosing.