The predominant mechanism for resistance to beta -lactam antibiotics in gram-negative bacteria is the synthesis of beta -lactamase. To meet this challenge, beta -lactams with greater beta -lactamase stability, including cephalosporins, carbapenems, and monobactams, were introduced in the 1980s. Resistance appeared initially in organisms such as Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Pseudomonas aeruginosa that could, by mutation, overproduce their chromosomal AmpC (also termed class C or group 1) beta -lactamase, thus providing resistance to both oxyimino- and 7- alpha -methoxycephalosporins and monobactams. Later, resistance appeared in bacterial species that lack an inducible AmpC enzyme, such as Klebsiella pneumoniae, Escherichia coli, Salmonella spp., and Proteus mirabilis, and this resistance was found to be mediated by plasmids encoding extended-spectrum beta -lactamases (ESBLs), which are enzymes that arose by mutations in TEM or SHV beta -lactamases of more limited hydrolytic capacity.