title: Development of new polymyxin derivatives for multi-drug resistant Gram-negative infections.
abstract: Over the last decade, there has been a resurgence of interest in polymyxins owing to the rapid rise in multi-drug resistant Gram-negative bacteria against which polymyxins offer a last-resort treatment. Although having excellent antibacterial activity, the clinical utility of polymyxins is limited by toxicity, especially renal toxicity. There is much interest therefore in developing polymyxin analogues with an improved therapeutic index. This review describes recent work aimed at improving the activity and/or reducing the toxicity of polymyxins. Consideration to providing activity against emerging strains with reduced susceptibility to polymyxins is also made.
authors.affiliation: Cantab Anti-infectives Ltd., BioPark Hertfordshire, Welwyn Garden City, Hertfordshire, UK.
authors.forename: Pamela
authors.initials: P
authors.lastname: Brown
authors.affiliation: Cantab Anti-infectives Ltd., BioPark Hertfordshire, Welwyn Garden City, Hertfordshire, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dawson
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D011113:Polymyxins / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D011113:Polymyxins