title: Pharmacokinetics/pharmacodynamics of colistin and polymyxin B: are we there yet?
abstract: 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.
authors: Monash Biomedicine Discovery Institute, Department of Microbiology, School of Biomedical Sciences, Monash University, Melbourne, VIC, Australia; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia.
authors: Thien B
authors: TB
authors: Tran
authors: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia.
authors: Tony
authors: T
authors: Velkov
authors: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia.
authors: Roger L
authors: RL
authors: Nation
authors: Laboratory of Antimicrobial Pharmacodynamics, Department of Pharmacy Practice, University of Buffalo, Buffalo, NY, USA; Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC, USA.
authors: Alan
authors: A
authors: Forrest
authors: Laboratory of Antimicrobial Pharmacodynamics, Department of Pharmacy Practice, University of Buffalo, Buffalo, NY, USA.
authors: Brian T
authors: BT
authors: Tsuji
authors: Centre for Medicine Use and Safety, Monash University, Melbourne, VIC, Australia.
authors: Phillip J
authors: PJ
authors: Bergen
authors: Monash Biomedicine Discovery Institute, Department of Microbiology, School of Biomedical Sciences, Monash University, Melbourne, VIC, Australia; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia. Electronic address: Colistin.Polymyxin@gmail.com.
authors: Jian
authors: J
authors: Li
mesh_terms: D058186:Acute Kidney Injury; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D003091:Colistin / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology; D006801:Humans; D011112:Polymyxin B / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D011112:Polymyxin B; D003091:Colistin
keywords: Nephrotoxicity; Pharmacodynamics; Pharmacokinetics; Polymyxins