Comparison of the composition and in vitro activity of polymyxin B products

John K. Diep, Jenna Covelli, Rajnikant Sharma, Donna M. Ruszaj, Keith S. Kaye, Jian Li, Robert M. Straubinger, Gauri G. Rao

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4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)365-371
Number of pages7
JournalInternational Journal of Antimicrobial Agents
Volume52
Issue number3
DOIs
Publication statusPublished - 2018

Keywords

  • LC-MS/MS
  • Multidrug resistance
  • PK/PD
  • Polymyxin B
  • UV fingerprinting

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