Antimicrobial Activity and Toxicity of the Major Lipopeptide Components of Polymyxin B and Colistin: Last-line Antibiotics against Multidrug-Resistant Gram-negative Bacteria.

Journal: ACS infectious diseases
Published Date: Sep 4, 2015

Abstract

Polymyxin B and colistin are currently used as a 'last-line' treatment for multidrug-resistant Gram-negative bacteria. However very little is known about the pharmacological differences between polymyxin B, polymyxin B, colistin A, colistin B, the major cyclic lipopeptides components present in polymyxin B and colistin products. Here, we report on the and antimicrobial activity and toxicity of these major lipopeptide components. All four lipopeptides had comparable MICs (<0.125-4 mg/L) against a panel of clinical Gram-negative isolates. They also had comparable antimicrobial activity (Δlog CFU/mL >-3) and nephrotoxicity (mild to moderate histological damage) in mouse models. However, polymyxin B and colistin A showed significantly higher (> 3-fold) apoptotic effect on human kidney proximal tubular HK-2 cells than polymyxin B2 and colistin B, respectively. Compared to the commercial polymyxin and colistin products, the individual lipopeptide components had slightly more antimicrobial activity. Our results highlight the need to re-assess pharmacopoeial standards for polymyxins B and colistin and to standardize the composition of the different commercial products of polymyxin antibiotics.

Authors

  • Kade D Roberts
    Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville 3052, Victoria, Australia; Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville 3052, Victoria, Australia.
  • Mohammad A K Azad
  • Jiping Wang
  • Andrew S Horne
    Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville 3052, Victoria, Australia.
  • Philip E Thompson
    Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville 3052, Victoria, Australia.
  • Roger L Nation
    Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville 3052, Victoria, Australia.
  • Tony Velkov
  • Jian Li
    Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Science, Fujian Agriculture and Forestry University, Fuzhou, China.

Keywords

No keywords available for this article.

External Resources

Popular Topics
Recent Journals