The bactericidal action of aztreonam results from the inhibition of bacterial cell wall synthesis due to a high affinity of aztreonam for penicillin binding protein 3 (PBP3). By binding to PBP3, aztreonam inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins. It is possible that aztreonam interferes with an autolysin inhibitor.
Aztreonam is a monocyclic beta-lactam antibiotic (a monobactam) originally isolated from Chromobacterium violaceum. Aztreonam exhibits potent and specific activity in vitro against a wide spectrum of gram-negative aerobic pathogens including Pseudomonas aeruginosa. It has no useful activity against gram-positive bacteria or anaerobes, but has very broad spectrum against gram-negative aerobes, including Pseudomonas aeruginosa. This has given it the nickname "the magic bullet for aerobic gram-negative bacteria". Aztreonam, unlike the majority of beta-lactam antibiotics, does not induce beta-lactamase activity and its molecular structure confers a high degree of resistance to hydrolysis by beta-lactamases (such as penicillinases and cephalosporinases) produced by most gram-negative and gram-positive pathogens; it is, therefore, usually active against gram-negative aerobic microorganisms that are resistant to antibiotics hydrolyzed by beta-lactamases. It is active against many strains that are multiply-resistant to other antibiotics, such as certain cephalosporins, penicillin, and aminoglycosides. Aztreonam maintains its antimicrobial activity over a pH range of 6 to 8 in vitro, as well as in the presence of human serum and under anaerobic conditions.
Approximately 6 to 16% metabolized to inactive metabolites by hydrolysis of the beta-lactam bond, resulting in an open-ring compound.
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