Potential role of non-antibiotics (helper compounds) in the treatment of multidrug-resistant Gram-negative infections: mechanisms for their direct and indirect activities.
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.
Martins
Marta
M
Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349-008 Lisboa, Portugal.
Dastidar
Sujata G
SG
Fanning
Seamus
S
Kristiansen
Jette E
JE
Molnar
Joseph
J
Pagès
Jean-Marie
JM
Schelz
Zsuzsanna
Z
Spengler
Gabriella
G
Viveiros
Miguel
M
Amaral
Leonard
L
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
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors