Synergistic Killing of Polymyxin B in Combination With the Antineoplastic Drug Mitotane Against Polymyxin-Susceptible and -Resistant : A Metabolomic Study.

Polymyxins are currently used as the last-resort antibiotics against multidrug-resistant . As resistance to polymyxins emerges in with monotherapy, combination therapy is often the only remaining treatment option. A novel approach is to employ the combination of polymyxin B with non-antibiotic drugs.

Novel Polymyxin Combination With Antineoplastic Mitotane Improved the Bacterial Killing Against Polymyxin-Resistant Multidrug-Resistant Gram-Negative Pathogens.

Due to limited new antibiotics, polymyxins are increasingly used to treat multidrug-resistant (MDR) Gram-negative bacteria, in particular carbapenem-resistant , , and . Unfortunately, polymyxin monotherapy has led to the emergence of resistance. Polymyxin combination therapy has been demonstrated to improve bacterial killing and prevent the emergence of resistance.

Pharmacokinetics/pharmacodynamics of colistin and polymyxin B: are we there yet?

The polymyxin antibiotics [colistin and polymyxin B (PMB)] are increasingly used as a last-line option for the treatment of infections caused by extensively drug-resistant Gram-negative bacteria. Despite having similar structures and antibacterial activity in vitro, the two clinically available polymyxins have very different pharmacological properties, as colistin (polymyxin E) is intravenously administered to patients in the form of an inactive prodrug colistin methanesulphonate (sodium). This review will discuss recent progress in the pharmacokinetics/pharmacodynamics and toxicity of colistin and PMB, the factors that affect their pharmacological profiles, and the challenges for the effective use of both polymyxins.

Agents of Last Resort: Polymyxin Resistance.

Polymyxin resistance is a major public health threat, as the polymyxins represent "last-line" therapeutics for Gram-negative pathogens resistant to essentially all other antibiotics. Improved understanding of mechanisms of, and risk factors for, polymyxin resistance, as well as infection prevention and stewardship strategies, together with optimization of dosing of polymyxins including in combination regimens, can help to limit the emergence and dissemination of polymyxin resistance.

Anthelmintic closantel enhances bacterial killing of polymyxin B against multidrug-resistant Acinetobacter baumannii.

Polymyxins, an old class of antibiotics, are currently used as the last resort for the treatment of multidrug-resistant (MDR) Acinetobacter baumannii. However, recent pharmacokinetic and pharmacodynamic data indicate that monotherapy can lead to the development of resistance. Novel approaches are urgently needed to preserve and improve the efficacy of this last-line class of antibiotics.