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

2015; American Chemical Society; Volume: 1; Issue: 11 Linguagem: Inglês

10.1021/acsinfecdis.5b00085

2373-8227

Kade D. Roberts, Mohammad Abul Kalam Azad, Jiping Wang, Andrew S. Horne, Philip E. Thompson, Roger L. Nation, Tony Velkov, Jian Li,

Antimicrobial agents and applications

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, colistin B, the major cyclic lipopeptides 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 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 re-assess pharmacopoeial standards for polymyxins B and colistin and to standardize the composition of the different commercial products of polymyxin antibiotics.