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Antimicrob Agents Chemother. 1982 Jun;21(6):950-6.

Mode of action of azthreonam.


Azthreonam (SQ 26,776) is a member of a new class of monocyclic beta-lactam antibiotics. In Escherichia coli, azthreonam caused filamentation at its lowest effective concentration (0.2 microgram/ml), a morphological effect identical to that observed with cephalothin. The penicillin-binding protein (PBP) profile indicated a very high affinity for PBP3 (complete binding at 0.1 microgram/ml), a moderate affinity for PBP1a (complete binding at 10 micrograms/ml), and poor affinities for PBP1b, PBP2, PBP4, and PBP5/6 (complete binding at greater than or equal to 100 micrograms/ml). Accordingly, azthreonam had poor activity against Streptomyces R61 DD-carboxypeptidase (50% inhibition, greater than 100 micrograms/ml) and E. coli peptidoglycan transpeptidase (50% inhibition, 100 micrograms/ml). Azthreonam also showed very high affinity for PBP3 (complete binding at 0.1 microgram/ml) in Proteus vulgaris, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa. In all four organisms, its PBP profile was similar to that observed in E. coli. It is concluded that azthreonam, although of novel structure, has a mode of action similar to that of cephalosporins, affecting specifically septation in E. coli and most likely other gram-negative bacteria.

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