Neurotoxicity and Nephrotoxicity
Colistin is an antibiotic which is being used more commonly now than when it was introduced because of its activity against multiresistant Gram-negative bacteria, especially Acinetobacter baumanii and Enterobacteriaceae producing extended spectrum β-lactamases. It had a bad reputation due to reports of neurotoxicity and nephrotoxicity. Recent studies have shown lower rates of nephrotoxicity than previously reported. However, in one of these reports, 7/42 patients with high serum creatinine values prior to colistin treatment developed renal failure.
White crystalline powder. Soluble in water, slightly soluble in ethanol or methanol, insoluble in acetone or ether. Hygroscopic, odorless, bitter.
Polymyxin E (colistin) is a complex of closely related cyclic peptides E1 and E2, with additional minor analogues. Polymyxin E is produced by Bacillus polymyxa var. colistinus, and is a highly basic, atypical cyclic peptide which incorporates the unusual amino acid, diaminobutyric acid. Head-to-tail coupling of lysine completes the macrocycle. Balancing the polar cyclic peptide is a hydrophobic tail with short chain fatty acids. Polymyxin E is a broad spectrum antibiotic active against Gram negative bacteria. The mechanism of action involves disruption of the bacterial outer membrane by a detergent-like effect.
Colistin (Polymyxin E) (16 mg/kg/day, i.p.) shows the enrichment of cell cycle arrest genes and suggests that injury or cellular stress caused by colistin is acting through p53 to inhibit cell cycle progression[1].
Colistin (16 mg/kg/day, i.p.) has elevated blood urea nitrogen (BUN), creatinine, and pathologic evidence of acute tubular necrosis and apoptosis[1].
| Animal Model: | C57/BL6 mice[1] |
| Dosage: | 16 mg/kg/day |
| Administration: | 16 mg/kg/day, i.p. |
| Result: | Detected apoptosis, necrosis PCNA staining in mice. |
