Colistin (polymixin E) is an antibiotic prescribed with resurging frequency for multidrug resistant gram negative bacterial infections. It is associated with nephrotoxicity in humans in up to 55% of cases. Little is known regarding genes involved in colistin nephrotoxicity. A murine model of colistin-mediated kidney injury was developed. C57/BL6 mice were administered saline or colistin at a do...

While colistin is considered a last resort for the treatment of multidrug-resistant Gram-negative bacterial infections, there has been an increase in its use due to the increasing prevalence of drug-resistant infections worldwide. The pharmacology of colistin is complex, and pharmacokinetic data are limited, especially in patients requiring renal replacement therapy. As a result, dosing for pat...

Colistin methanesulfonate (CMS), the inactive prodrug of colistin, is administered by inhalation for the management of respiratory infections. However, limited pharmacokinetic data are available for CMS and colistin following pulmonary delivery. This study investigates the pharmacokinetics of CMS and colistin following intravenous (i.v.) and intratracheal (i.t.) administration in rats and deter...

Acinetobacter baumannii has successfully developed resistance against all common antibiotics, including colistin (polymyxin E), the last universally active drug against this pathogen. The possible widespread distribution of colistin-resistant A. baumannii strains may create an alarming clinical situation. In a previous work, we reported differences in lethal mechanisms between polymyxin B (PXB)...

Despite the identification of Acinetobacter baumannii isolates that demonstrate susceptibility to only colistin, this antimicrobial agent was not available in Korea until 2006. The present study examined the outcomes of patients with multidrug resistant (MDR) Acinetobacter species bloodstream infection and who were treated with or without colistin as part of their regimen. The colistin group wa...

BACKGROUND Colistin resistance is of concern since it is increasingly needed to treat infections caused by bacteria resistant to all other antibiotics and has been associated with poorer outcomes. Longitudinal data from in vivo series are sparse. METHODS Under a quality-improvement directive to intensify infection-control measures, extremely drug-resistant (XDR) bacteria undergo phenotypic an...

Historically, the colistin has been thought to kill bacteria through membrane lysis. Here, we present an alternative mechanism that colistin induces rapid Paenibacillus polymyxa death through reactive oxygen species production. This significantly augments our understanding of the mechanism of colistin action, which is critical knowledge toward the yield development of colistin in the future.

Karvanen, M. 2013. Optimization of Colistin Dosage in the Treatment of Multiresistant Gram-negative Infections. Acta Universitatis Upsaliensis. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 889. 56 pp. Uppsala. ISBN 978-91-554-8640-2. As multidrug resistance in Gram-negative bacilli increases, the old antibiotic colistin has rapidly gained attention as on...

Extensively drug-resistant (XDR) Acinetobacter spp. have emerged as a cause of nosocomial infections, especially under conditions of intensive care. Unfortunately, resistance to colistin is increasing and there is a need for new therapeutic options. We aimed to study the effect of some novel combinations against XDR Acinetobacter baumannii in an in vitro pharmacokinetics-pharmacodynamics (PK/PD...

A multidrug-resistant Klebsiella pneumoniae isolate exhibiting heteroresistance to colistin was investigated. The colistin-resistant subpopulation harbored a single amino acid change (Asp191Tyr) in protein PhoP, which is part of the PhoPQ two-component system that activates pmrHFIJKLM expression responsible for l-aminoarabinose synthesis and polymyxin resistance. Complementation assays with a w...