期刊
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
卷 48, 期 6, 页码 592-597出版社
ELSEVIER
DOI: 10.1016/j.ijantimicag.2016.09.010
关键词
Polymyxins; Pharmacokinetics; Pharmacodynamics; Nephrotoxicity
资金
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH/NIAID) [R01 AI111965]
- NIH/NIAID [R01 AI111990]
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. Strategies are proposed for optimising their clinical utility based upon the recent pharmacological studies in vitro, in animals and patients. In the 'Bad Bugs, No Drugs' era, polymyxins are a critically important component of the antibiotic armamentarium against difficult-to-treat Gram-negative 'superbugs'. Rational approaches to the use of polymyxins must be pursued to increase their effectiveness and to minimise resistance and toxicity. (C) 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
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