title: Colistin: Revival of an Old Polymyxin Antibiotic.
abstract: Colistin (polymyxin E) is a positively charged deca-peptide antibiotic that disrupts the integrity of the outer membrane of the cell wall of gram-negative bacteria by binding to the lipid A moiety of lipopolysaccharides, resulting in cell death. The endotoxic activity of lipopolysaccharides is simultaneously inhibited. Colistin is increasingly being prescribed as rescue treatment for infections with multidrug-resistant bacilli. Nephrotoxicity and, to a lesser degree, neurotoxicity occur often during systemic colistin therapy, and have severely limited its application in the past. However, these side effects are largely reversible and can be managed through close monitoring. The prodrug colistimethate sodium (CMS) is less toxic and is, therefore, the preferred formulation for parenteral administration. Importantly, resistance to colistin seems to emerge often unless it is combined with another antibiotic, but further studies into this phenomenon are necessary. Pharmacokinetic and pharmacodynamic properties have received little attention, partly because of the physicochemical peculiarities of polymyxin antibiotics, especially their propensity to stick to other molecules and surfaces. The ratio between the area under the curve of free colistin and the pathogen's Minimal Inhibitory Concentration (MIC) best predicts microbiological and clinical responses, but more studies are needed in this area. Likewise, further standardization is needed in production and labeling of colistin formulations, and in the way the susceptibility of bacteria to colistin is determined.
authors.affiliation: *Medical Center Haaglanden; †Pharmacy The Hague Hospitals; ‡Centre for Human Drug Research, Leiden; §Haga Hospital, The Hague; ¶Erasmus University Medical Center, Rotterdam; and ‖University Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Anneke C
authors.initials: AC
authors.lastname: Dijkmans
authors.forename: Erik B
authors.initials: EB
authors.lastname: Wilms
authors.forename: Ingrid M C
authors.initials: IM
authors.lastname: Kamerling
authors.forename: Willem
authors.initials: W
authors.lastname: Birkhoff
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Ortiz-Zacarías
authors.forename: Cees
authors.initials: C
authors.lastname: van Nieuwkoop
authors.forename: Henri A
authors.initials: HA
authors.lastname: Verbrugh
authors.forename: Daan J
authors.initials: DJ
authors.lastname: Touw
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D003091:Colistin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004357:Drug Synergism; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; C004691:colistinmethanesulfonic acid; D003091:Colistin