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...

Colistin sulfate (polymixin E) is an antibiotic prescribed with increasing frequency for severe Gram-negative bacterial infections. As nephrotoxicity is a common side effect, the discovery of pharmacogenomic markers associated with toxicity would benefit the utility of this drug. Our objective was to identify genetic markers of colistin cytotoxicity that were also associated with expression of ...

Rifkind, David (University of Colorado Medical Center, Denver), and John D. Palmer. Neutralization of endotoxin toxicity in chick embryos by antibiotics. J. Bacteriol. 92:815-819. 1966.-Three cationic cyclic polypeptide antibiotics, polymyxin B sulfate colistin sulfate, and tyrocidine hydrochloride, were shown to neutralize endotoxin lethality in chick embryos. The neutralizing potency of these...

The condition of cells in Pseudomonas aeruginosa biofilms was monitored via the electrochemical detection of the electro-active virulence factor pyocyanin in a fabricated microfluidic growth chamber coupled with a disposable three electrode cell. Cells were exposed to 4, 16, and 100 mg L(-1) colistin sulfate after overnight growth. At the end of testing, the measured maximum peak current (and t...

Chemical arrays were employed to screen ligands for HtpG, the prokaryotic homologue of Hsp (heat-shock protein) 90. We found that colistins and the closely related polymyxin B interact physically with HtpG. They bind to the N-terminal domain of HtpG specifically without affecting its ATPase activity. The interaction caused inhibition of chaperone function of HtpG that suppresses thermal aggrega...

In a recent article, Garonzik et al. (4) importantly advanced our knowledge of the pharmacokinetics (PK) of colistin methanesulfonate (CMS) and the active drug that it forms, colistin. In their elegant population PK study of critically ill patients, the authors demonstrated that creatinine clearance (CLCR) significantly affects the total body clearance of CMS and colistin (4). It is important t...

In a recent article, Garonzik et al. (4) importantly advanced our knowledge of the pharmacokinetics (PK) of colistin methanesulfonate (CMS) and the active drug that it forms, colistin. In their elegant population PK study of critically ill patients, the authors demonstrated that creatinine clearance (CLCR) significantly affects the total body clearance of CMS and colistin (4). It is important t...

In a recent article, Garonzik et al. (4) importantly advanced our knowledge of the pharmacokinetics (PK) of colistin methanesulfonate (CMS) and the active drug that it forms, colistin. In their elegant population PK study of critically ill patients, the authors demonstrated that creatinine clearance (CLCR) significantly affects the total body clearance of CMS and colistin (4). It is important t...

Colistin is a decapeptide antibiotic with a narrow spectrum of antibacterial activity mainly against Gram-negative microorganisms (Ziv,1981). It is also able to inactivate bacterial toxins in vitro (Ziv et al., 1978). That is why it is commonly used for treatment of diseases caused by sensitive Gram-negative bacteria (Roy et al., 1997; van Hattum et al., 2000).Despite the fact that this antibio...