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Pharmacology of polymyxins: new insights into an 'old' class of antibiotics

Tony Velkov1, Kade D Roberts, Roger L Nation

  • 1Drug Delivery, Disposition & Dynamics, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade Parkville 3052, Victoria, Australia.

Future Microbiology
|May 25, 2013
PubMed

Insights

Antibiotic resistance in Gram-negative bacteria is a major threat. This review covers polymyxin B and colistin, crucial last-line treatments, detailing their chemistry, activity, and resistance mechanisms to guide future drug development and optimize current use.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Rising antibiotic resistance in Gram-negative bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae) poses a global health crisis.
  • A limited pipeline for new antibiotics necessitates the strategic use of existing last-line agents like colistin and polymyxin B.
  • These 'superbugs' are increasingly resistant, complicating treatment of severe infections.

Purpose of the Study:

  • To review advancements in polymyxin chemistry, antibacterial mechanisms, and resistance over the past decade.
  • To explore structure-activity relationships and pharmacokinetic/pharmacodynamic properties of polymyxins.
  • To guide the development of novel polymyxin-like lipopeptides and optimize current polymyxin therapy.

Main Methods:

  • Literature review of polymyxin research from the last 10 years.
  • Analysis of studies on polymyxin chemistry and antibacterial mechanisms.
  • Examination of data on resistance, structure-activity relationships, and pharmacokinetics/pharmacodynamics.

Main Results:

  • Significant progress has been made in understanding polymyxin properties and interactions.
  • Structure-activity relationship studies are crucial for developing new polymyxin-based drugs.
  • Pharmacokinetic/pharmacodynamic principles are vital for effective clinical use and resistance mitigation.

Conclusions:

  • Novel polymyxin-like lipopeptides are needed to combat resistant Gram-negative 'superbugs'.
  • Optimizing polymyxin use via pharmacokinetic/pharmacodynamic principles is essential to preserve their efficacy and minimize resistance.
  • Continued research into polymyxin chemistry and biology is critical in the 'Bad Bugs, No Drugs' era.

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