Cephalosporins

The first cephalosporins, cephalothin and cephaloridine, modestly expanded the spectrum of ampicillin and possessed relative stability to staphylococcal β-lactamase. Some later derivatives offered little, if any improvement, but Cephazolin exhibited the unusual characteristic of achieving enhanced concentrations in bile and Cephamandole offered partial resistance to some enterobacteria β-lactamases (Greenwood, 1995).

The first generation agents were active against Methicillin-susceptible S. aureus, Penicillin-susceptible S. pneumoniae and other common Gram positive bacteria as well as many community acquired Gram negative bacilli (Reese et al., 2000).

The second generation agent’s cephamandole and later cefuroxime were developed because of their activity against ampicillin-susceptible and resistant H. influenzae and many S. pneumoniae, while cefoxitin was the first cephalosporin to be active against anaerobes (Reese et al., 2000).

The third generation agents were initially touted as having enhanced Gram negative activity, including activity against hospital acquired pathogens and P. aeruginosa. In addition, the once daily ceftriaxone agent has significant Gram positive activity (Resse et al., 2000).

Cefepime has sometimes been called a fourth generation agent, but it
may be better summarized as a hybrid of cefotaxime and ceftazidime (Marshall and Blair, 1999).

The cephalosporins resemble the penicillins both in their structure and their mode of action. They inhibit mucopeptide synthesis, cause the accumulation of cell wall precursors, and the formation of morphologically aberrant forms of bacteria. They are generally resistant to the β-lactamases produced by most Gram-positive bacteria, although they are themselves effective inducers of these enzymes. Cephaloridine is, however, slowly hydrolysed by the penicillinase of s. aureus (Benner et al. 1965, Ridley and Phillips 1965).