Multidrug-resistant (MDR) Klebsiella pneumoniae may require combination therapy. We systematically investigated bacterial killing with colistin and doripenem mono- and combination therapy against MDR K. pneumoniae and emergence of colistin resistance. A one-compartment in vitro pharmacokinetic/pharmacodynamic model was employed over a 72-h period with two inocula (∼10(6) and ∼10(8) CFU/ml); a c...

OBJECTIVES The aim of this study was to evaluate the effect of colistin methanesulphonate (CMS) dose on CMS and colistin pharmacokinetics in rats. METHODS Three rats per group received an intravenous bolus of CMS at a dose of 5, 15, 30, 60 or 120 mg/kg. Arterial blood samples were drawn at 0, 5, 15, 30, 60, 90, 120, 150 and 180 min. CMS and colistin plasma concentrations were determined by li...

INTRODUCTION Colistin use has increased over the last ten years because of multidrug-resistant microorganisms. The aim of this study was to compare the clinical and microbiological efficacy of colistin alone or in combination with sulbactam or carbapenem in the treatment of ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) and extremely drug-resistant (XDR) A. baumannii. ...

OBJECTIVES To define the steady-state pharmacokinetics of colistin methanesulphonate and colistin in patients with cystic fibrosis (CF) following intravenous administration of the former. MATERIALS AND METHODS The study was conducted in 12 patients with CF following intravenous administration of colistin methanesulphonate (1.63-3.11 mg/kg) every 8 h for at least 2 days. On the day of study, f...

Colistin, an "old" polymyxin antibiotic, is increasingly being used as last-line treatment against infections caused by multidrug-resistant gram-negative bacteria. It is administered in patients, parenterally or by inhalation, as its inactive prodrug colistin methanesulfonate (CMS). Scientifically based recommendations on how to optimally dose colistin in critically ill patients have become ava...

Purpose: To evaluate colistin use according to global standard drug consumption in intensive care units of a referral hospital in Shiraz, Iran Methods: A prospective, interventional study was performed during an 11 month period on 100 patients admitted to ICUs of a teaching hospital being treated with colistin for at least 3 subsequent doses. Required demographic, clinical, and paraclinical dat...

23 We characterized carbapenem resistance mechanisms among 12 Klebsiella 24 pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) clinical isolates, and 25 evaluated their effects on the activity of 2and 3-drug combinations of colistin, 26 doripenem and ertapenem. All isolates were resistant to ertapenem and doripenem; 27 75% (9/12) were resistant to colistin. Isolates belonged to ST258 clo...

This in vitro study aimed to determine the activity of colistin plus sulbactam and colistin plus fosfomycin against carbapenem-resistant A. baumannii (CRAB). Fifteen clinical isolates were obtained from patients admitted to Phyathai II International Hospital, Bangkok, Thailand, from August 2014 to April 2015. The antimicrobial susceptibilities of colistin, sulbactam, and fosfomycin were evaluat...

OBJECTIVES To determine the disposition of colistin methanesulphonate (CMS) and colistin following intravenous (iv) administration of CMS in rats. METHODS Five rats received a single iv bolus of 15 mg/kg CMS. Plasma concentrations of CMS and of colistin formed by the hydrolysis of CMS were determined by HPLC. The pharmacokinetic parameters of CMS and colistin were calculated using non-compart...

Synergy between colistin and the signal peptidase inhibitor MD3 was tested against isogenic mutants and clinical pairs of Acinetobacter baumannii isolates. Checkerboard assays and growth curves showed synergy against both colistin-susceptible strains (fractional inhibitory concentration index [FICindex] = 0.13 to 0.24) and colistin-resistant strains with mutations in pmrB and phosphoethanolamin...