Emergence of resistance in gram-negative bacteria: a risk of broad-spectrum beta-lactam use

A number of new beta-lactam antibiotics have been developed to overcome bacterial resistance to older agents. Such resistance usually is caused by plasmid-mediated, constituently produced beta-lactamases. Second- and third-generation cephalosporins, ureidopenicillins, acylamino penicillins, and monobactams generally are resistant to hydrolysis by these enzymes. However, inducible beta-lactamases may confer resistance to these antibiotics. This induction may occur spontaneously or in response to cefoxitin or other beta-lactam agents. The mechanisms by which inducible enzymes produce this resistance are reviewed and implications for the prophylactic and therapeutic use of newer beta-lactams are considered.