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Polymyxin B
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
Polymyxin B is a mixture of polymyxins B1 and B2, obtained from Bacillus polymyxa strains, with antibacterial activity. They are basic polypeptides of about eight amino acids and have cationic detergent action on cell membranes. Polymyxin B is used for infections with gram-negative organisms, notably for treatment of infections of the urinary tract, meninges, and blood stream, caused by susceptible strains of Pseudomonas aeruginosa (1). It is often used in combination (compounded) with other antibiotics such as bacitracin or neomycin, especially in ophthalmic and ear preparations.
Relationships between Inflammation and Immunopathology of Malaria
Published in Mary M. Stevenson, Malaria: Host Responses to Infection, 2017
The nature of the trigger for TNF release in malaria is also under investigation. The group from the Middlesex Hospital, London, has recently shown that mouse malarial parasites can in vitro serve as well as endotoxin in triggering TNF release.78 In these experiments, polymyxin B was added to control for endotoxin contamination. An obvious approach for several groups will now be to see if the various defined malarial antigens that have been genetically engineered by laboratories attempting to make malarial vaccines will also trigger macrophages to release TNF.
Endotoxin Detection in Body Fluids: Chemical Versus Bioassay Methodology
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Polymyxin B and derivatives thereof are a class of antibiotics with well-known high binding affinity for LPS (14). Not surprisingly, this property has led to their use in the development of endotoxin detection assays (44,45). One interesting assay for endotoxin in blood cleverly uses red blood cells present in the sample as the indicator (hemagglutination) (44–46). This assay employs a chemical conjugate of a monoclonal antibody or a lectin specific for red blood cells, which in themselves do not cause coagulation, and PMB or a derivative thereof. When the test reagent (SimpliRED Endotoxin Test) is mixed with a whole blood sample, the antibody-PMB conjugate coats the red blood cells. In the presence of endotoxin, binding to the PMB portion of the complex will cause visible hemagglutination. In a recent study (46), SimpliRED was compared to LAL and clinical variables associated with sepsis. The SimpliRED test had the advantage of being rapid (2 minutes), which would potentially be of value for “bedside” analysis of blood samples for endotoxin. Sensitivity of the test was 1.2 EU/ml. In this comparative set of studies, the LAL method employed a chromogenic LAL on heat/diluted PRP samples collected in heparin tubes. Although the sensitivity of the LAL reagent was 0.005 EU/ml, the + /—level chosen for the assay was 5 EU/ml. Of all clinical outcomes studied, the SimpliRED test showed a positive correlation for patients with multiorgan dysfunction, while the LAL did not. These results are somewhat surprising in that SimpliRED and LAL should both be measuring relative endotoxin levels. It is possible, as the authors suggest, that the heat-extraction procedure or the physical state of circulating endotoxin caused a discrepancy between the two assays. It is more likely that + /—levels selected (1.2 vs. 5) and the collection/test control had more influence on these results. Additional studies are needed here, but the goal of a rapid, simple assay is commendable.
Colistin-associated Stevens-Johnson syndrome and toxic epidermal necrolysis reactions: a retrospective case-non-case pharmacovigilance study
Published in Expert Opinion on Drug Safety, 2022
Richard Tang, Vrishali L. Lopes, Aisling R. Caffrey
The results of our study with recent FAERS data show that colistin was not listed as a primary suspect drug for any SJS/TEN adverse event reports, and therefore this association could not be assessed. When evaluating SJS/TEN adverse event reports where colistin was listed as a secondary suspect drug, reporting rates were almost 30 times higher compared with all other drugs. Existing literature does not mention any association between SJS/TEN and colistin. Further, this reaction is not listed in colistin package inserts [19–22]. A similar association was observed with polymyxin B, a 25-times higher reporting rate than other drugs. However, there was only one report of SJS/TEN and polymyxin B, resulting in a wide confidence interval, which limits any conclusions that can be made from this finding.
Synergistic effect of silver nanoparticles and polymyxin B against biofilm produced by Pseudomonas aeruginosa isolates of pus samples in vitro
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Muhammad Salman, Rizwana Rizwana, Hayat Khan, Iqbal Munir, Muhammad Hamayun, Aquib Iqbal, Abdul Rehman, Khalid Amin, Ghayour Ahmed, Majid Khan, Ajmal Khan, Faiz Ul Amin
Emerging of MDR bacterial strains is the main issue. Pseudomonas aeruginosa is one of the leading MDR among other bacteria. As these bacteria are resistant to antibiotics, thus for treatment of infections, new strategies are required. Polymyxin B antibiotic in the previous years were used to treat infections but its use was banned due to its nephrotoxicity and neurotoxicity. In the present situation, due to the strong resistance of bacteria towards other antibiotics, Polymyxin B is the last choice of drug to treat infections. Our study is based on the synergistic effect of AgNPs combined with Polymyxin B in order to reduce the dose of Polymyxin B, thus decreasing its toxicity towards the host. It is demonstrated that NPs possesses broad-spectrum antibacterial properties against both gram-positive and gram-negative bacteria [29]. Some studies showed the concentration dependent antimicrobial activity of AgNPs against E. coli and P. aeruginosa is also investigated [30].
The use of polymyxins to treat carbapenem resistant infections in neonates and children
Published in Expert Opinion on Pharmacotherapy, 2019
Reenu Thomas, Sithembiso Velaphi, Sally Ellis, A. Sarah Walker, Joseph F. Standing, Paul Heath, Mike Sharland, Daniele Dona’
Polymyxin B (PMB) has also been increasingly used worldwide for treating infections with CRO. Polymyxin B shares very similar antimicrobial properties and chemical structure to colistin. They differ only by one amino acid in their peptide ring, where the D-leucine of colistin is replaced by phenylalanine of PMB. Data on the PK of PMB in neonates are limited, and most data have been derived from adult studies. The major difference between colistin and PMB is the form in which they are administered intravenously. Unlike colistin, PMB is administered directly in its active form and is eliminated by non-renal pathways. Manchandani et al examined PMB PK in 35 adults and investigated factors influencing PK variability. The mean elimination half-life of PMB was 10.1 hours, and the maximum concentration achieved was 3.4 ug/ml at 24 hours. They showed that covariates such as creatinine clearance and body weight of patients might not be accurate predictors of PMB PK [42]. Another PK study on PMB, by Sandri et al, involved 24 critically ill adults [43,44]. Intravenous doses used in this study ranged from 0.45 mg/kg/day to 3.38 mg/kg/day. In this study the average steady-state plasma concentration was 2.79 ± 0.90 mg/L (range, 0.68–4.88 mg/L). Higher and quicker steady state concentrations were achieved compared to CMS (from previous PK data), and fewer dosing adjustments were required. There are currently no recommended neonatal doses of PMB.