The Cephalosporin Antibiotic Agents— III. Third-Generation Cephalosporins

Abstract

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).

Ceftazidime/Avibactam: Who Says You Can’t Teach an Old Drug New Tricks?

“…This also produces a zwitterion allowing for enhanced gramnegative cell membrane penetration and increased water solubility (6). The carboxypropyl group found on the aminothiazolyloximino side chain at position 7 also confers additional stability against β-lactamases produced by Enterobacteriaceae and P. aeruginosa (7). Ceftazidime exerts its activity by binding to penicillin-binding proteins (PBPs) within the cell wall, primarily PBP-3, interfering with cell division and leading to cell death (8).…”