Cephalosporin

Lore & Background

Guy Newton and Edward Abraham at the Sir William Dunn School of Pathology at the University of Oxford isolated cephalosporin C.

Reader's Guide

Cephalosporins are a major class of antibiotics that disrupt bacterial cell wall synthesis by mimicking the D-Ala-D-Ala site, irreversibly inhibiting penicillin-binding proteins. They are classified into generations, with first-generation agents active predominantly against Gram-positive bacteria, and later generations showing increased activity against Gram-negative organisms, though often with reduced Gram-positive activity. Fourth-generation cephalosporins have true broad-spectrum activity. The classification into generations is commonly practiced but imprecise; for example, Japan does not recognize a fourth generation, and some drugs are classified differently between countries. Resistance can involve reduced affinity of PBPs or acquisition of β-lactam-insensitive PBPs. Some strains of Citrobacter freundii, Enterobacter cloacae, Neisseria gonorrhoeae, Escherichia coli, and others have developed resistance. Fifth-generation cephalosporins (e.g., ceftaroline) are effective against MRSA, Listeria, and Enterococcus faecalis.

Did You Know?

• Several cephalosporins with a methylthiotetrazole side chain can cause hypoprothrombinemia and a disulfiram-like reaction with alcohol.