Emergence of Resistance in Gram-Negative Bacteria: A Risk of Broad-Spectrum Beta-Lactam Use

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