Beta-lactam antibiotics inhibit the growth of sensitive bacteria by inactivating enzymes located in the bacterial cell membrane, known as penicillin binding proteins, which are involved in cell wall synthesis. These antibiotics are generally bactericidal against susceptible organisms.
The major mechanism of resistance to the beta-lactam antibiotics in clinical isolates is production of enzymes that cleave penicillins (penicillinases), cephalosporins (cephalosporinases), or both (beta-lactamases). Decreased penetration to the plasma membrane target site and alterations in the penicillin binding proteins are other mechanisms of resistance.
Enterobacter, indole-positive Proteus, Serratia, and Citrobacter produce an inducible chromosomal beta-lactamase that may be difficult to detect on initial susceptibility testing but can mediate resistance to all currently available beta-lactams other than carbapenems.
The most common plasmid-mediated beta-lactamases in Gram negative bacteria mediate resistance to penicillins and first- and some second-generation cephalosporins. Extended spectrum plasmid-mediated beta-lactamases can additionally cleave later-generation cephalosporins and aztreonam. These plasmids can transfer to other species and genera.
Use of beta-lactams is associated with various adverse effects, including IgE-mediated allergic reactions, rash, diarrhea, renal toxicity, and other hypersensitivity and immune-mediated reactions. The penicillins are the most common antibiotics to cause encephalopathy and high doses of beta-lactams can cause seizures.