[Antipseudomonal activity of carbapenem antibiotics].
To date, three carbapenem antibiotics have been introduced for clinical use, and they can be structurally classified into two types. One is a natural type that has the naturally-occurring carbapenem skeleton and a strongly basic (cationic) moiety in the C-2 side chain, like imipenem or panipenem. The other is a new generation carbapenem, meropenem, which has the 1 beta-methyl carbapenem skeleton and a less basic group in the C-2 side chain. It was reported that there were some significant differences among these two types of carbapenems concerning the antimicrobial profile, especially the antipseudomonal activity. Since Pseudomonas aeruginosa was one of the target pathogens of carbapenem antibiotics, these facts prompted us to overview the different mode of action among imipenem, panipenem and meropenem and clarify the structure-activity relationships of carbapenems with regard to the antipseudomonal activities. In this article, we discuss that both the chemical structure and the physicochemical properties of carbapenems greatly influence a variety of antipsedomonal actions including MIC, affinity for PBPs, outer membrane permeability, interaction with various beta-lactamases and multidrug efflux systems etc., and that the cationic center in the C-2 side chain plays an important role in antipseudomonal activities. This review will be helpful in developing new types of antipseudomonal carbapenems and/or new clinical applications of carbapenem antibiotics for treating pseudomonal infection.
Sunagawa
M
M
Kanazawa
K
K
Nouda
H
H
D015780:Carbapenems / Q000737:chemistry / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D004352:Drug Resistance, Microbial; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013329:Structure-Activity Relationship; D001618:beta-Lactamases / Q000378:metabolism
D015780:Carbapenems; D001618:beta-Lactamases