title: Cellular and molecular aspects of drugs of the future: meropenem.
abstract: Meropenem, first synthesized in the late eighties, has become one of the most important beta-lactam antibiotics of the carbapenem subclass used for the treatment of a variety of life-threatening infections. Due to its unique chemical structure, meropenem is not inactivated by the kidney dehydropeptidase I and the majority of microbial beta-lactamases. Its antimicrobial activity is based on its high affinity for the majority of cell wall-synthesizing enzymes, the so-called penicillin-binding proteins, of Gram-positive and -negative bacteria. However, bacteria have evolved several approaches to resist meropenem: (i) by reducing the affinity of the penicillin-binding proteins for the antibiotics, (ii) by decreasing the permeability of the outer membrane of Gram-negative bacteria, (iii) by using efflux pumps, and (iv) by activating zinc-dependent carbapenemases. Meropenem has a low toxicity profile and, in contrast to imipenem, no central nervous system toxicity.
authors.affiliation: Department of Internal Medicine, Inselspital Bern, Bern, Switzerland. pcottagn@insel.ch
authors.forename: P
authors.initials: P
authors.lastname: Cottagnoud
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D005544:Forecasting; D006801:Humans; D000077731:Meropenem; D011485:Protein Binding; D013845:Thienamycins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D013845:Thienamycins; D000077731:Meropenem