Interaction of azthreonam and related monobactams with beta-lactamases from gram-negative bacteria.

Antimicrobial Agents and Chemotherapy
K BushR B Sykes

Abstract

Monobactams containing 3 beta-aminothiazolyl oxime side chains (SQ 81,377, SQ 81,402, azthreonam, and SQ 26,917) have poor affinities for the broad-spectrum beta-lactamases TEM-2 and K1. Addition of a 4-methyl substituent significantly increased stability to hydrolysis by these enzymes. P99 cephalosporinase from Enterobacter cloacae was strongly inhibited by the monobactams. Interaction of azthreonam with the P99 enzyme in equimolar concentrations resulted in a single covalent complex which retained less than 3% catalytic activity. On incubation, enzymatic activity was slowly regained. Chromatographic studies of the incubation mixtures revealed the presence of a single ring-opened product. It is concluded that monobactams act as poor substrates for broad-spectrum beta-lactamases and tight-binding competitive substrates for the P99 beta-lactamase.

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Citations

Aug 1, 1987·European Journal of Clinical Microbiology·D M Livermore
Jan 1, 1985·Pharmacology & Therapeutics·R B SykesE A Swabb
Jan 1, 1985·Pharmacology & Therapeutics·H Nikaido
Jul 1, 1989·Diagnostic Microbiology and Infectious Disease·T Sawai, A Yamaguchi
Jan 1, 1985·Biotechnology & Genetic Engineering Reviews·A Coulson
Jun 27, 2007·Antimicrobial Agents and Chemotherapy·Anne Marie QueenanKaren Bush
Dec 10, 2009·Antimicrobial Agents and Chemotherapy·Karen Bush, George A Jacoby
Jul 1, 1983·Antimicrobial Agents and Chemotherapy·A YamaguchiT Sawai
Mar 1, 1984·Antimicrobial Agents and Chemotherapy·A YamaguchiT Sawai
Mar 1, 1984·Antimicrobial Agents and Chemotherapy·Y SainoS Mitsuhashi
Apr 1, 1985·Antimicrobial Agents and Chemotherapy·K BushR B Sykes
May 1, 1985·Antimicrobial Agents and Chemotherapy·K Murakami, T Yoshida
Aug 1, 1985·Antimicrobial Agents and Chemotherapy·J Romero-VivasM García de la Torre
Jul 1, 1986·Antimicrobial Agents and Chemotherapy·K Bush, R B Sykes
Nov 1, 1986·Antimicrobial Agents and Chemotherapy·G J CuchuralF P Tally
Feb 1, 1987·Antimicrobial Agents and Chemotherapy·S K TanakaR B Sykes
Jan 1, 1988·Antimicrobial Agents and Chemotherapy·N X Chin, H C Neu
Mar 1, 1989·Antimicrobial Agents and Chemotherapy·K Bush
Mar 1, 1989·Antimicrobial Agents and Chemotherapy·K Bush
Nov 1, 1990·Antimicrobial Agents and Chemotherapy·G A Papanicolaou, A A Medeiros
Jan 1, 1991·Antimicrobial Agents and Chemotherapy·F BellidoR E Hancock
May 1, 1991·Antimicrobial Agents and Chemotherapy·J M Lacroix, C Walker
Jun 1, 1995·Antimicrobial Agents and Chemotherapy·K BushA A Medeiros
Jan 13, 2010·Clinical Microbiology Reviews·Sarah M Drawz, Robert A Bonomo
Sep 16, 2010·Expert Opinion on Therapeutic Patents·Karen Bush, Mark J Macielag
Jul 1, 1989·The Journal of Pharmacy and Pharmacology·K MatsuyamaT Muramatsu
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Feb 8, 1985·The American Journal of Medicine·R B Sykes, D P Bonner
Feb 8, 1985·The American Journal of Medicine·J D Allan, R C Moellering
Feb 25, 1988·The New England Journal of Medicine·G R Donowitz, G L Mandell

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