title: Optimizing Polymyxin Combinations Against Resistant Gram-Negative Bacteria.
abstract: Polymyxin combination therapy is increasingly used clinically. However, systematic investigations of such combinations are a relatively recent phenomenon. The emerging pharmacodynamic (PD) and pharmacokinetic (PK) data on CMS/colistin and polymyxin B suggest that caution is required with monotherapy. Given this situation, polymyxin combination therapy has been suggested as a possible way to increase bacterial killing and reduce the development of resistance. Considerable in vitro data have been generated in support of this view, particularly recent studies utilizing dynamic models. However, most existing animal data are of poor quality with major shortcomings in study design, while clinical data are generally limited to retrospective analysis and small, low-power, prospective studies. This article provides an overview of clinical and preclinical investigations of CMS/colistin and polymyxin B combination therapy.
authors.affiliation: Centre for Medicine Use and Safety, Monash University, Melbourne, Australia.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Bergen
authors.affiliation: Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA.
authors.forename: Zackery P
authors.initials: ZP
authors.lastname: Bulman
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia.|Centre for Medicine Use and Safety, Monash University, Melbourne, Australia.
authors.forename: Cornelia B
authors.initials: CB
authors.lastname: Landersdorfer
authors.affiliation: Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Smith
authors.affiliation: Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Lenhard
authors.affiliation: Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL, USA.
authors.forename: Jürgen B
authors.initials: JB
authors.lastname: Bulitta
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Nation
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA. btsuji@buffalo.edu.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Tsuji
keywords: Colistin; Colistin methanesulfonate; Combination; Pharmacodynamic; Polymyxin B; Polymyxins