Cephalosporin antimicrobial agents and related compounds.

Cephalosporins are broad-spectrum antimicrobial agents that are often used empirically to treat suspected bacterial infections and also to treat culture-proven infections due to selected gram-positive and gram-negative microorganisms. Cephalosporins differ widely in their spectrum of activity, susceptibility to beta-lactamases, serum half-life, and penetration of the central nervous system. In general, the first-generation and second-generation agents are most active against staphylococci and streptococci, and the third-generation agents are most active against the Enterobacteriaceae and Pseudomonas. As a group, cephalosporins have a favorable profile of toxicity in comparison with other antimicrobial agents. The development of bacterial resistance has affected all steps of the cephalosporin mechanism of action, including production of beta-lactamases, alterations in penicillin-binding proteins, and modification of the cell wall. New cephalosporins are among the most expensive pharmaceutical agents in use today. Maintaining expertise in the choice and use of these agents will remain a challenge to physicians as additional investigational cephalosporins continue to be developed and introduced into clinical practice.