Colistin is increasingly used as a salvage therapy for nosocomial infections caused by multidrug-resistant Gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. However, the available pharmacokinetic (PK) data for colistin are limited to guide dosing. The aim of this study was to develop a population PK model of colistin and to identify the optimal dosage regimens f...

Colistin, administered intravenously as its inactive prodrug colistin methanesulfonate (CMS), is increasingly used as last-line therapy to combat multidrug-resistant Gram-negative bacteria. CMS dosing needs to be adjusted for renal function. The impact of continuous ambulatory peritoneal dialysis (CAPD) on the pharmacokinetics of both CMS and colistin has not been studied. No CMS dosing recomme...

Combination therapy may be required for multidrug-resistant (MDR) Pseudomonas aeruginosa. The aim of this study was to systematically investigate bacterial killing and emergence of colistin resistance with colistin and doripenem combinations against MDR P. aeruginosa. Studies were conducted in a one-compartment in vitro pharmacokinetic/pharmacodynamic model for 96 h at two inocula (~10(6) and ~...

The aim of this study was to evaluate the biopharmaceutical behavior of colistin methanesulfonate (CMS) with special focus on colistin presystemic formation after CMS nebulization in rats. CMS was administered (15 mg x kg(-1) of body weight) either intravenously for systemic pharmacokinetic studies (n = 6) or as an intratracheal nebulization for systemic pharmacokinetic studies (n = 5) or for C...

Intravenous colistin methanesulfonate (CMS) is increasingly the last line of defense for multidrug-resistant gram-negative bacteria and is now being used as “salvage” therapy in critically ill patients (1, 7, 9, 11). CMS is converted in vivo to colistin, and these two entities have substantially different pharmacokinetics, antibacterial activities, and toxicities (7), and therefore it is import...

INTRODUCTION The increasing prevalence of multiresistant Gram-negative strains in intensive care units (ICUs) has recently rekindled interest in colistin, a bactericidal antibiotic that was used in the 1960s for treatment of infections caused by Gram-negative bacilli. We conducted the present observational study to evaluate the efficacy of intravenous colistin in the treatment of critically ill...

The global rise of multidrug-resistant gram-negative bacteria represents an increasing threat to patient safety. From the first observation of a carbapenem-resistant gram-negative bacteria a global spread of extended-spectrum beta-lactamases and carbapenemases producing Klebsiella pneumoniae has been observed. Treatment options for multidrug-resistant K. pneumoniae are actually limited to combi...

Acinetobacter baumannii (American Type Culture Collection strain 19606) acquires mutations in the pmrB gene during the in vitro development of resistance to colistin. The colistin-resistant strain has lower affinity for colistin, reduced in vivo fitness (competition index, .016), and decreased virulence, both in terms of mortality (0% lethal dose, 6.9 vs 4.9 log colony-forming units) and surviv...

Acinetobacter baumannii had emerged as an important nosocomial and opportunistic pathogen worldwide. To assess the evolution of colistin resistance in A. baumannii and its effect on bacterial fitness, we exposed five independent colonies of A. baumannii ATCC 17978 to increasing concentrations of colistin in agar (4/5) and liquid media (1/5). Stable resistant isolates were analyzed using whole g...

A sensitive and reliable liquid chromatographic method was developed and validated for the determination of colistin concentrations in mouse brain homogenate. With a mobile phase consisting of acetonitrile-tetrahydrofuran-water (50:25:25 [vol/vol]) at a flow rate of 1 ml/min, a linear correlation between peak area and colistin concentration was observed over the concentration range of 93.8 to 3...