Third-generation and investigational cephalosporins: I. Structure-activity relationships and pharmacokinetic review.

The structure-relationships and pharmacokinetic properties of the new second- and third-generation cephalosporins are reviewed. The new second-generation cephalosporins include ceforanide, cefotiam, and cefuroxime. The third-generation cephalosporins include cefmenoxime, cefoperazone, cefotaxime, cefsulodin, ceftazidime, ceftizoxime, ceftriaxone, and moxalactam. These new cephalosporins are semisynthetic analogs with different chemical substitutions on a 7-aminocephalosporanic nucleus. As a result of these chemical modifications, improvements in the antibacterial spectrum as well as pharmacokinetic properties have occurred. In general, the new cephalosporins have longer half-lives, higher and prolonged serum concentrations, and increased cerebrospinal fluid penetration. Selected cephalosporins also have increased biliary tract concentrations. A classification scheme for these new agents, based on generation and susceptibility to Pseudomonas aeruginosa, is presented.