Novel Carbapenem Derivative SF2103A: Studies on the Mode of Beta-lactamase Inactivation

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 1984 Mar 1

PMID 6372682

Citations 1

Authors

A Yamaguchi

T Hirata

T Sawai

Affiliations

Soon will be listed here.

Abstract

A novel carbapenem, SF2103A, is a strong inhibitor of various types of beta-lactamase. Equimolar concentrations of SF2103A completely inactivated the cephalosporinases of Proteus vulgaris and Citrobacter freundii and type Ib and type II penicillinases mediated by R plasmids in a progressive manner. The inactivation of the two penicillinases and P. vulgaris cephalosporinase was apparently irreversible; however, when the inactivated enzymes were separated from excess SF2103A by gel filtration, they showed very slow reactivation. The hydrolysis of SF2103A by these three beta-lactamases was below the limit of detection. It is concluded that SF2103A acts as a tight-binding competitive inhibitor for the penicillinases and P. vulgaris cephalosporinase. In contrast, the inactivation of C. freundii cephalosporinase by SF2103A was evidently reversible. The rate constant of reactivation of the enzyme was compatible with the turnover rate of the enzyme in the steady state of SF2103A hydrolysis. Thus, SF2103A simply acts as a poor substrate for C. freundii cephalosporinase.

Citing Articles

In vitro and pharmacokinetic properties of the carbapenems.

Wise R Antimicrob Agents Chemother. 1986; 30(3):343-9.

PMID: 3535659 PMC: 180556. DOI: 10.1128/AAC.30.3.343.

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