Work

Pharmacology of Polymyxins: New Insights into an ‘Old‘ Class of Antibiotics

Year: 2013

Type: review

Abstract: Increasing antibiotic resistance in Gram-negative bacteria, particularly in Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae, presents a global medical challenge. No new antibiotics will be available for these 'superbugs' in the near future due to the dry antibiotic discovery pipeline. Colistin and polymyxin B are increasingly used as the last-line therapeutic options for treatment of infections caused by multidrug-resistant Gram-negative bacteria. This article surveys the significant progress over the last decade in understanding polymyxin chemistry, mechanisms of antibacterial activity and resistance, structure-activity relationships and pharmacokinetics/pharmacodynamics. In the 'Bad Bugs, No Drugs' era, we must pursue structure-activity relationship-based approaches to develop novel polymyxin-like lipopeptides targeting polymyxin-resistant Gram-negative 'superbugs'. Before new antibiotics become available, we must optimize the clinical use of polymyxins through the application of pharmacokinetic/pharmacodynamic principles, thereby minimizing the development of resistance.

Source: Future Microbiology

DOI: 10.2217/fmb.13.39

Authors: Tony Velkov, Kade D Roberts, Roger L Nation, Philip E Thompson, Jian Li

Institution: Monash University

Language: English

Topic: Antibiotic Resistance in Bacteria

Subfield: Molecular Medicine

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institute of Allergy and Infectious Diseases