Cephalosporins are β-lactam drugs that, like penicillins, also inhibit the cross-linking of peptidoglycan. The structures, however, are different. Cephalosporins have a six-membered ring adjacent to the β-lactam ring and are substituted in two places on the 7-aminocephalosporanic acid nucleus (Figure 1), whereas penicillins have a five-membered ring and are substituted in only one place.
Fig1. Cephalosporins. A: The 7-aminocephalosporanic acid nucleus. B: The two R groups in the drug cephalothin.
The first-generation cephalosporins are active primarily against gram-positive cocci (Table 1). Similar to the penicillins, new cephalosporins were synthesized with expansion of activity against gram-negative rods as the goal. These new cephalosporins have been categorized into second, third, and fourth generations, with each generation having expanded coverage against certain gram-negative rods. The fourth- and fifth-generation cephalosporins have activity against many gram-positive cocci as well.
Table1. Activity of Selected Cephalosporins
Cephalosporins are effective against a broad range of organ isms, are generally well tolerated, and produce fewer hypersensitivity reactions than do the penicillins. Despite the structural similarity, a patient allergic to penicillin has only about a 10% chance of being hypersensitive to cephalosporins also. Most cephalosporins are the products of molds of the genus Cephalosporium; a few, such as cefoxitin, are made by the actinomycete Streptomyces.
The inactivation of cephalosporins by β-lactamases (cephalosporinases) is an important clinical problem. β-Lactamase inhibitors such as tazobactam and avibactam are combined with certain cephalosporins to prevent inactivation of the cephalosporin. The US Food and Drug Administration (FDA) approved the combination of ceftazidime/avibactam (Avycaz) and ceftolozane/tazobactam (Zerbaxa) for the treatment of intra-abdominal infections and complicated urinary tract infections (UTIs) caused by antibiotic-resistant gram-negative rods.
