title: Potential role of non-antibiotics (helper compounds) in the treatment of multidrug-resistant Gram-negative infections: mechanisms for their direct and indirect activities.
abstract: Multidrug resistance in Gram-negative bacteria is now known to be primarily caused by overexpression of efflux pumps that extrude unrelated antibiotics from the periplasm or cytoplasm of the bacterium prior to their reaching their intended target. This review focuses on a variety of agents that have been shown to be efflux pump inhibitors (EPIs) and which, if used as 'helper compounds' in combination with antibiotics to which the organism is initially resistant, may produce the required cure. Although not all of the EPIs may serve a helper role owing to their toxicity, they may nevertheless serve as lead compounds.
authors.affiliation: Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349-008 Lisboa, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Martins
authors.forename: Sujata G
authors.initials: SG
authors.lastname: Dastidar
authors.forename: Seamus
authors.initials: S
authors.lastname: Fanning
authors.forename: Jette E
authors.initials: JE
authors.lastname: Kristiansen
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnar
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Pagès
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Schelz
authors.forename: Gabriella
authors.initials: G
authors.lastname: Spengler
authors.forename: Miguel
authors.initials: M
authors.lastname: Viveiros
authors.forename: Leonard
authors.initials: L
authors.lastname: Amaral
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology*; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors