Colistin adheres to a range of materials, including plastics in labware. The loss caused by adhesion influences an array of methods detrimentally, including MIC assays and time-kill experiments. The aim of this study was to characterize the extent and time course of colistin loss in different types of laboratory materials during a simulated time-kill experiment without bacteria or plasma proteins present. Three types of commonly used large test tubes, i.e., soda-lime glass, polypropylene, and polystyrene, were studied, as well as two different polystyrene microplates and low-protein-binding microtubes. The tested concentration range was 0.125 to 8 mg/liter colistin base. Exponential one-phase and two-phase functions were fitted to the data, and the adsorption of colistin to the materials was modeled with the Langmuir adsorption model. In the large test tubes, the measured start concentrations ranged between 44 and 102% of the expected values, and after 24 h, the concentrations ranged between 8 and 90%. The half-lives of colistin loss were 0.9 to 12 h. The maximum binding capacities of the three materials ranged between 0.4 and 1.1 μg/cm, and the equilibrium constants ranged between 0.10 and 0.54 ml/μg. The low-protein-binding microtubes showed start concentrations between 63 and 99% and concentrations at 24 h of between 59 and 90%. In one of the microplates, the start concentrations were below the lower limit of quantification at worst. In conclusion, to minimize the effect of colistin loss due to adsorption, our study indicates that low-protein-binding polypropylene should be used when possible for measuring colistin concentrations in experimental settings, and the results discourage the use of polystyrene. Furthermore, when diluting colistin in protein-free media, the number of dilution steps should be minimized.
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http://dx.doi.org/10.1128/AAC.00857-17 | DOI Listing |
Biomed Pharmacother
January 2025
Departament de Farmacologia, Toxicologia i Química Terapèutica, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona (UB), Av. de Joan XXIII, 27-31, Barcelona 08028, Spain; Institut de Neurociències, Universitat de Barcelona (UB), Passeig de la Vall d'Hebron, 171, Barcelona 08035, Spain; Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Instituto de Carlos III, Av. Monforte de Lemos, 3-5, Madrid 28029, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari Sant Joan de Reus, Av. Josep Laporte, 2, Reus 43204, Spain. Electronic address:
The rise of antimicrobial resistance has made necessary the increase of the antibacterial arsenal against multidrug-resistant bacteria. In this context, colistin has re-emerged as a first-line antibiotic in critical situations despite its nephro- and neuro- toxicity at peripheral level. However, the mechanism underlying its toxicity remains unknown, particularly in relation to the central nervous system (CNS).
View Article and Find Full Text PDFPathogens
November 2024
Smart Animal Bio Institute, Dankook University, Cheonan 31116, Republic of Korea.
The emergence of antibiotic-resistant () is a pressing threat in clinical settings. Colistin is currently a widely used treatment for multidrug-resistant , serving as the last line of defense. However, reports of colistin-resistant strains of have emerged, underscoring the urgent need to develop alternative medications to combat these serious pathogens.
View Article and Find Full Text PDFAntimicrob Agents Chemother
December 2024
Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain.
The pipeline for new drugs against multidrug-resistant remains limited, highlighting the urgent need for innovative treatments. New strategies, such as membrane-targeting molecules acting as adjuvants, aim to enhance antibiotic effectiveness and combat resistance. RW01, a cyclic peptide with low antimicrobial activity, was selected as an adjuvant to enhance drug efficacy through membrane permeabilization.
View Article and Find Full Text PDFFront Cell Infect Microbiol
December 2024
Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
Introduction: Murepavadin is an antimicrobial peptide (AMP) in clinical development that selectively targets LptD and whose resistance profile remains unknown. We aimed to explore genomic modifications and consequences underlying murepavadin and/or colistin susceptibility.
Methods: To define genomic mechanisms underlying resistance, we performed two approaches: 1) a genome-wide association study (GWAS) in a clinical collection (n=496), considering >0.
Cell Rep
January 2025
Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK. Electronic address:
Pseudomonas aeruginosa produces a wealth of virulence factors whose production is controlled via an intricate regulatory systems network. Here, we uncover a major player in the evolution and regulation of virulence that enhances host colonization and antibiotic resistance. By characterizing a collection of mutants lacking the stringent response (SR), a system key for virulence, we show that the loss of the central regulator MexT bypasses absence of the SR, restoring full activation of virulence pathways.
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