NAGANO R, YAMADA K, SUGIMOTO Y, IMAMURA H, HASHIZUME T, MORISHIMA H; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 299 (abstract no. 402).
Tsukuba Res. Inst. Banyu Pharmaceutical, Tsukuba, JAPAN.
Clinically available beta-lactamase inhibitors are known to be useful for potentiating beta-lactam antibiotics against Class A beta-lactamase producers, while efforts have been continued to obtain a potent inhibitor of Class B and Class C beta-lactamases. Carbapenem-derived J-110,441, which has benzothienylthio moiety on C-2 position of 1beta-methylcarbapenem nucleus and very weak anti-gram-negative activity, was identified as a potent inhibitor of IMP-1 beta-lactamase, a transferable Class B metallo-beta-lactamase. Interestingly, J-110,441 inhibited various Class B metallo-beta-lactamases such as IMP-1 coded on the transferable bla[IMP] gene, CcrA from Bacteroides fragilis, and L-1 from Stenotrophomonas maltophilia with K[i] values of 0.0037micro-M, 0.24micro-M, and 1.02micro-M, respectively. Further studies showed that J-110,441 inhibited plasmidic TEM type Class A serine-beta-lactamase and chromosomal Class C serine-beta-lactamase from Enterobacter cloacae with K[i] values of 1.02 micro-M and 0.0062 micro-M, respectively. In the whole cell susceptibility testing, the MICs of imipenem for IMP-1-producing clinical isolates were reduced in combination with J-110,441. Similarly, ceftazidime-resistance caused by high expression of chromosomal Class C beta-lactamase was sensitized in the presence of J-110,441. In this paper, we will describe the interaction of J-110,441 with various beta-lactamases including Class B and Class C beta-lactamases and examine its capacity to achieve a possible new type of beta-lactamase inhibitor. [table: see text]
Publication Types:
Keywords:
- Bacteroides fragilis
- Carbapenems
- Ceftazidime
- Cesium
- Enterobacter cloacae
- Enzyme Inhibitors
- Imipenem
- Microbial Sensitivity Tests
- Monobactams
- beta-Lactamases
- classification
Other ID:
UI: 102246651
From Meeting Abstracts