Population pharmacokinetics and pharmacodynamics of fosfomycin in non-critically ill patients with bacteremic urinary infection caused by multidrug-resistant Escherichia coli

[Objectives] To describe the population pharmacokinetics of fosfomycin for patients with bacteraemic urinary tract infection (BUTI). The analysis identified optimal regimens on the basis of pharmacodynamic targets and assessed the adequacy of Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) susceptibility breakpoints for Escherichia coli.[Methods] Data of 16 patients with BUTI caused by multidrug-resistant E. coli (FOREST clinical trial) received intravenous fosfomycin (4 g every 6 hours) were analysed. A population pharmacokinetic analysis was performed, and Monte Carlo simulations were undertaken using 4 g every 6 hours and 8 g every 8 hours. The probability of pharmacodynamic target attainment was assessed using pharmacodynamic targets for E. coli for static effect, 1-log drop in bacterial burden and resistance suppression.[Results] Sixty-four plasma samples were collected over a single dosing interval (day 2 or 3 after starting fosfomycin treatment). Fosfomycin concentrations were highly variable. Pharmacodynamic target attainment analysis showed mild improvement by increasing fosfomycin dosing (4 g every 6 hours vs. every 8 hours). These dosages showed success for decreasing 1-log bacterial burden in 89% to 96% (EUCAST breakpoints) and 33% to 54% (CLSI breakpoints) of patients, but they were unable to reach bacterial resistance suppression targets.[Conclusions] Fosfomycin concentrations are highly variable—a fact partially explained by renal impairment. The present work supports the use of 4 g every 6 hours as an effective regimen for the treatment of non–critically ill patients with BUTI caused by multidrug-resistant E. coli, as higher dosages might increase toxicity but may not significantly increase efficacy. The current information may suggest that fosfomycin susceptibility breakpoints need to be reappraised.Supported in part by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (PI13/01282 and PI16/01824), Spain; and by Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0015/0010; RD16/0016/0001), cofinanced by European Development Regional Fund ‘A way to achieve Europe,’ Operative Program Intelligent Growth 2014–2020. FDP was supported by a VPPIUS fellowship from the University of Seville. WWH was supported by a National Institute of Health Research Clinician Scientist award (CS/08/08).Peer reviewe

A novel spectrophotometric method for the determination of copper ion by using a salophen ligand, N,N'-disalicylidene-2,3-diaminopyridine

WOS: 000411700000016this study, a novel, selective and highly sensitive spectrophotometric method has been developed for the determination of copper(II) by using a new chromogenic reagent N,N'-bissalicylidene-2,3-diaminopyridine (H2IF). The absorbance was measured at lambda max = 414 nm. Experimental conditions were optimized, and Beer's law was observed in the concentration range of 6.35-318 mu g L-1 of copper. The molar absorptivity of the complex was calculated and found to be 1.46 x 10(5) L mol(-1) cm(-1). The detection and quantification limits were calculated and found to be 6.38 mu g L-1 and 21.27 mu g L-1, respectively. The calculated relative standard deviation (n = 5) was 0.62% for a standard solution including 63.5 mu g L-1 copper( II). The interference effects of the common ions have been studied and the statistical assessment of the obtained results is presented. The developed method was applied for the determination of copper in water samples. The reliability and accuracy of the developed method was proven by the analysis of a waste water standard. (C) 2017 The Authors. Production and hosting by Elsevier B.V. on behalf of Taibah University