Abstract
Resistance to cefotaxime (CTA) and ceftriaxone (CTR) in Enterobacter cloacae and Pseudomonas aeruginosa was investigated in several strains which are susceptible or resistant to these agents. All strains produced a chromosomally mediated cephalosporinase of the Richmond type 1. beta-Lactamases in susceptible strains were inducible, whereas resistant strains produced the enzymes constitutively. CTA and CTR were very poor substrates but potent inhibitors of all enzymes. Binding to, rather than hydrolysis by, beta-lactamases was assumed to be a major reason for resistance, and combination experiments supported this assumption. Dicloxacillin, which did not inhibit the growth and which was a poor inducer but a strong inhibitor of these beta-lactamases, exerted strong synergistic activity when combined with CTA or CTR in strains which produced large amounts of beta-lactamase constitutively. Cefoxitin, on the other hand, poorly active alone, but a good inducer, strongly antagonized CTA or CTR in susceptible strains producing inducible enzymes. In marked contrast to CTA and CTR were the findings with cefsulodin. Cefsulodin was active against CTA- and CTR-resistant Pseudomonas, and its activity was hardly influenced by dicloxacillin or cefoxitin. Since cefsulodin was found to have a very low affinity for all cephalosporinases, these findings corroborate the assumption that binding of nonhydrolyzable cephalosporins, rather than hydrolysis by cephalosporinases, may play an important role in resistance to these agents and other newer cephalosporins in Enterobacteriaceae, as well as in other gram-negative bacteria.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference30 articles.
1. Ro 13-9904, a long-acting broad-spectrum cephalosporin: in vitro and in vivo studies;Angehrn P.;Antimicrob. Agents Chemother.,1980
2. CP-45,899, a beta-lactamase inhibitor that extends the antibacterial spectrum of beta-lactams: initial bacteriological characterization;English A. R.;Antimicrob. Agents Chemother.,1978
3. Mechanism of synergistic effects of P-lactam antibiotic combinations on gram-negative bacilli;Farrar W. E.;Antimicrob. Agents Chemother.,1973
4. P-Lactamase proceeds via an acyl-enzyme intermediate. Interaction of the Escherichia coli RTEM enzyme with cefoxitin;Fisher J.;Biochemistry,1980
5. Beta-lactamase stability of HR 756, a novel cephalosporin, compared to that of cefuroxime and cefoxitin;Fu K. P.;Antimicrob. Agents Chemother.,1978
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