Antimicrobial Activity and Toxicity of the Major Lipopeptide Components of Polymyxin B and Colistin: Last-Line Antibiotics against Multidrug-Resistant Gram-Negative Bacteria
- 4 September 2015
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Infectious Diseases
- Vol. 1 (11), 568-575
- https://doi.org/10.1021/acsinfecdis.5b00085
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 B1, polymyxin B2, colistin A, and colistin B, the major cyclic lipopeptide components present in polymyxin B and colistin products. Here, we report on the in vitro and in vivo antimicrobial activity and toxicity of these major lipopeptide components. All four lipopeptides had comparable minimum inhibitory concentrations (MICs) ( −3) and nephrotoxicity (mild to moderate histological damage) in mouse models. However, polymyxin B1 and colistin A showed significantly higher (>3-fold) in vitro 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 in vivo antimicrobial activity. Our results highlight the need to reassess pharmacopoeial standards for polymyxin B and colistin and to standardize the composition of the different commercial products of polymyxin antibiotics.Keywords
Funding Information
- National Institute of Allergy and Infectious Diseases (R01 AI098771)
- National Health and Medical Research Council (ID 1026109)
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