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Published on: January 9, 2018
Comparison of the composition and in vitro activity of polymyxin B products
John K Diep1, Jenna Covelli2, Rajnikant Sharma3
1Division of Pharmaceutics and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214, USA.
Abstract:
A number of companies manufacture polymyxin B using United States Pharmacopeia (USP) metrics, rather than chemical composition, to report biological activity. Given that polymyxin B contains several different components, it is unknown whether pharmacokinetic and pharmacodynamic variability exists between the different brands and whether USP metrics capture this variability. Here we investigated the composition of polymyxin B obtained from four manufacturers (Sigma-Aldrich, AK Scientific, USP and MP Biomedicals) and evaluated their rate and extent of killing against multidrug-resistant Acinetobacter baumannii and Klebsiella pneumoniae using in vitro static time-kill experiments. Ultraviolet (UV) fingerprinting and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed similarities and differences between component distributions. The significant differences between products, based on UV fingerprinting and LC-MS/MS, did not translate into pharmacodynamic differences at the three concentrations evaluated. The aggregate polymyxin B concentration, rather than that of the individual components, influences overall bacterial killing.
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