New polymyxin derivatives that display improved efficacy in animal infection models as compared to polymyxin B and colistin

Medicinal Research Reviews
Martti Vaara

Abstract

Polymyxin B and colistin (polymyxin E) are bactericidal pentacationic lipopeptides that act specifically on Gram-negative bacteria, first by disrupting their outermost permeability barrier, the outer membrane (OM), and then damaging the cytoplasmic membrane. The discovery of both polymyxin B and colistin was published independently by three laboratories as early as in 1947. They were subsequently used in intravenous therapy. Unfortunately, they also exhibit significant and dose-limiting nephrotoxicity. Therefore, polymyxins were reserved as agents of last-line defense. The emergence of extremely multiresistant strains has now forced clinicians to reinstate polymyxins in the therapy of severe infections. However, the current dosage regimens lead to insufficient drug concentrations in serum and clinicians have been advised to use larger doses, which further increases the risk of nephrotoxicity. Very recently, the interest in developing better tolerated and more effective polymyxins has grown. This review focuses on describing four development programs that have yielded novel derivatives that are more effective than the old polymyxins in animal infection models. Compounds from three programs are superior to the old polymyxins in t...Continue Reading

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Citations

Apr 25, 2019·Antibiotics·Justin R LenhardKeith S Kaye
Nov 26, 2019·Annals of the New York Academy of Sciences·Craig R MacNairEric D Brown
Mar 3, 2020·Environmental Microbiology·Yingbo ShenYang Wang
Dec 21, 2018·JCI Insight·Elijah J WeberEdward J Kelly
Apr 2, 2020·Antibiotics·Martti VaaraEdgars Liepinsh
Jun 20, 2019·Odontology·Shunya OkaAkane Imai
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Aug 14, 2019·Frontiers in Microbiology·Martti Vaara
Jul 17, 2018·Current Medicinal Chemistry·Annamaria SandomenicoMenotti Ruvo
Jan 16, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Martti Vaara
May 18, 2018·ACS Infectious Diseases·Lori L Burrows

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