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

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.

The development and validation of a simple liquid chromatography-tandem mass spectrometry method for polymyxin B1 and B2 quantification in different matrices.

Polymyxin B has resurfaced as a last-line treatment for multi-drug resistant Gram-negative bacteria. Accurate characterization and quantification of polymyxin B components is necessary to optimize this therapy. We developed and validated a robust, straightforward LC-MS/MS method to quantify polymyxin B1 and B2, the primary polymyxin B components, in various matrices (cation-adjusted Mueller-Hinton broth (CAMHB), human and rat plasma).

Polymyxin B in Combination with Rifampin and Meropenem against Polymyxin B-Resistant KPC-Producing Klebsiella pneumoniae.

Safe and effective therapies are urgently needed to treat polymyxin-resistant KPC-producing Klebsiella pneumoniae infections and suppress the emergence of resistance. We investigated the pharmacodynamics of polymyxin B, rifampin, and meropenem alone and as polymyxin B-based double and triple combinations against KPC-producing K. pneumoniae isolates.

A hybrid Markov chain-von Mises density model for the drug-dosing interval and drug holiday distributions.

Lack of adherence is a frequent cause of hospitalizations, but its effects on dosing patterns have not been extensively investigated. The purpose of this work was to critically evaluate a novel pharmacometric model for deriving the relationships of adherence to dosing patterns and the dosing interval distribution. The hybrid, stochastic model combines a Markov chain process with the von Mises distribution.