The third-“generation” cephalosporin antibiotics (Table 1) represent a class of agents with an expanded gram-negative spectrum of activity beyond that of the first- and second-“generation” cephalosporins. Greater stability to beta-lactamases produced by gram-negative organisms confers to these agents a greater bactericidal action against the Enterobacteriaceae. Large bacterial inocula (105/ml) in vitro significantly increase the minimum inhibitory and bactericidal concentrations (MIC and MBC) explaining treatment failures with these agents in infections associated with large numbers of organisms. The pharmacokinetic features of some of the agents allow prolongation of dosing intervals, and enhanced tissue penetration amplifies their clinical utility in infections distant from the bloodstream (eg, meningitis).

The first article in this series discussed the cephalosporin antibiotic agents as a class, including the similarities in their structure, antimicrobial action, and toxicity. Part II focuses on the difference between commercially available first- and second-“generation” agents.The cephalosporins are classified using various criteria, including vulnerability to beta-lactamase hydrolysis and antibacterial activity. The latter classification is based on the in vitro activity of the individual agents, with each succeeding “generation” possessing a greater spectrum of activity than the previous generation(s).