Interrelationship Between Pharmacokinetics and Pharmacodynamics in Determining Dosage Regimens for Broad-spectrum Cephalosporins

The broad-spectrum cephalosporins exhibit time-dependent bactericidal activity and produce prolonged postantibiotic effects only with staphylococci. The duration of time that serum levels exceed the minimum inhibitory concentration (MIC) is the important pharmacodynamic parameter correlating with efficacy for these drugs. Maximal efficacy for cephalosporins in several animal infection models is approached when serum levels are above the MIC for 60%-70% of the dosing interval for Enterobacteriaceae and streptococci and for 40%-50% of the dosing interval for Staphylococcus aureus. Based on MIC90 values of 0.5 microgram/ml for enteric bacilli and 4 micrograms/ml for S. aureus, these time above MIC goals can be easily met in infected and/or elderly patients following 1-2 g of cefotaxime at 12-h intervals. Full knowledge of the interrelationships between pharmacokinetics and pharmacodynamics is important for determining effective dosage regimens for the broad-spectrum cephalosporins.