Monobactams

Study of the structural basis of activity of early β-lactam compounds led to the expectation that compounds in which the β-lactam ring was not strained by fusion to another ring would be inactive as antimicrobial agents. However, some natural monocyclic β-lactam antibiotics, including certain monobactams and nocardicins, are active in vitro against Gram-negative bacteria, including Ps. aeruginosa.
In contrast to penicillins and cephalosporins, which are commonly produced by fungi and actinomycetes, naturally occurring monobactams are produced by bacteria. Because of their simplicity of structure, they can be obtained easily by total synthesis. In some monobactams the β-lactam ring carries an α-methoxy group, similar to the β-lactamase-stable cephamycins, but the first monobactam used therapeutically, and the only one to achieve modest commercial acceptability, aztreonam, lacks this substituent.
Monobactams exhibit no useful activity against Grampositive organisms or strict anaerobes because of poor binding to PBPs . Activity against Gram-negative bacteria, including Ps. aeruginosa, is due to tight binding to PBP 3 (Esch. coli numbering). As a result, the organisms convert to filaments, which slowly lyse.
Monobactams are hydrolyzed poorly by many serine β-lactamases and all metallo-β-lactamases, but can be hydrolyzed by ESBLs and serine carbapenemases. Group 1 cephalosporinases have high affinities for non-methoxylated monobactams, whereas group 2 β-lactamases generally bind aztreonam poorly. They are generally not inducers of the group 1 chromosomal cephalosporinases of Gram-negative bacteria.