Discovery of Novel Polymyxin-Like Antibiotics

Tony Velkov, Kade D. Roberts

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Otherpeer-review

6 Citations (Scopus)

Abstract

The antimicrobial lipopeptides polymyxin B and colistin (polymyxin E) are used as a ‘last-line’ therapy for infections caused by multidrug-resistant (MDR) Gram-negative pathogens. However, their effective use as antibiotic drugs in the clinical setting is still plagued by significant toxicity issues, in particular their potential for nephrotoxicity. Furthermore, resistance to the polymyxins has begun to emerge in the clinic, which implies a total lack of antibiotics for the treatment of life-threatening infections caused by the Gram-negative ‘superbugs’. This chapter details our current understanding of polymyxin structure-activity relationships as well as recent pre-clinical and clinical drug development efforts aimed at generating new polymyxin antibiotics with improved safety and efficacy.

Original languageEnglish
Title of host publicationPolymyxin Antibiotics
Subtitle of host publicationFrom Laboratory Bench to Bedside
EditorsJian Li, Roger L. Nation, Keith S. Kaye
Place of PublicationSwitzerland
PublisherSpringer
Chapter20
Pages343-362
Number of pages20
ISBN (Electronic)9783030163730
ISBN (Print)9783030163716
DOIs
Publication statusPublished - 2019

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1145
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Drug discovery
  • Llipid A
  • Nephrotoxicity
  • Polymyxin
  • Structure-activity relationship

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