In view of reports of colistin-induced neurotoxicity in infected patients, the aim of this study was to assess whether the integrity of the blood-brain barrier (BBB) and the brain uptake of colistin are altered in the presence of systemic Pseudomonas aeruginosa infection. Bacteremia was confirmed 8 h after intramuscular administration of P. aeruginosa ATCC 27853 to Swiss Outbred mice, at which ...

Intravenous inoculation of 6.2 x 10(10) to 6.7 x 10(10)Pseudomonas aeruginosa organisms into rhesus monkeys 5 days after intratracheal inoculation of 2.0 to 2.5 mg of vincristine sulfate resulted in fatal sepsis in 8 of 10 untreated monkeys. When similarly infected monkeys were treated intramuscularly with 2.5 mg of colistin or 50 mg of carbenicillin per kg per day, all three monkeys in each tr...

KOIKE e t al. reported that a cationic acylpeptide antibiotic, colistin (polymyxin E) caused the formation of blebs on the outer layer of the Gram-negative bacterial cell envelope". They have also reported that colistin affects the cytoplasmic membrane, leads to leakage of cytoplasmic 260 nm-absorbing materials and has specific bursting-activity on spheroplasts of Gram-negative bacteria'). On t...

Infections caused by carbapenem-resistant, Gram-negative bacteria are an increasing clinical challenge, since the antimicrobial treatment options are often limited to colistin methanesulfonate. No data are available regarding the pharmacokinetics of colistin in pleural fluid. We report the case of a 92-year old man with ventilator-associated pneumonia and pleurisy caused by Acinetobacter bauman...

In this simplified microbiological assay for serum vitamin B12, Lactobacillus leichmanii (NCIB 8117) adapted to tolerate high concentrations (500 mg/L) of the polymyxin antibiotic colistin sulfate is used. Results were similar in parallel experiments in which we used both the parent strain of L. leichmanii (NCIB 8117), and the new adapted strain. Evaluation of assay performance showed excellent...

The purpose of this study was to investigate the pharmacokinetic properties of colistin following intrapulmonary administration of colistin sulfate in rats. Colistin was infused or delivered in nebulized form at a dose of 0.35 mg/kg of body weight in rats, and plasma drug concentrations were measured for 4 h after administration. Bronchoalveolar lavages (BAL) were also conducted at 0.5, 2, and ...

OBJECTIVES An optimized dosing regimen of the prodrug of colistin, colistin methanesulphonate (CMS), against resistant Pseudomonas aeruginosa is needed to ensure effective bacterial killing. The objectives of this study were to develop a pharmacokinetic (PK)/pharmacodynamic (PD) model that characterizes the time course of the antibacterial activity of colistin against P. aeruginosa in a static ...

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...

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...