Colistin sulfate
[CAS# 1264-72-8]

Identification

• Classification: API >> Antibiotics >> Other antibiotics
• Name: Colistin sulfate
• Synonyms: N-[3-Amino-1-[[1-[[3-amino-1-[[6,9,18-tris(2-aminoethyl)-3-(1-hydroxyethyl)-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]carbamoyl]propyl]carbamoyl]-2-hydroxy-propyl]carbamoyl]propyl]-5-methyl-heptanamide sulfate
• Molecular Formula: 2(C₅₂H₉₈N₁₆O₁₃).5(H₂SO₄)
• Molecular Weight: 2801.26
• CAS Registry Number: 1264-72-8
• EC Number: 215-034-3
• SMILES: [S](=O)(=O)(O)O.N1[C@H](C(=O)NCC[C@@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C1=O)CCN)CCN)CC(C)C)CC(C)C)CCN)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CCCCC(CC)C)CCN)[C@H](O)C)CCN)[C@H](O)C

Properties

• Melting point: 200-220 °C

Safety Data

• Hazard Symbols: GHS06 Danger
• Risk Statements: H301
• Safety Statements: P264-P270-P301+P316-P321-P330-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - repeated exposure	STOT RE	1	H372

• Transport Information: UN 2811

Discovery and Applications

Colistin sulfate is a polypeptide antibiotic that belongs to the polymyxin class, primarily used to combat infections caused by Gram-negative bacteria. It is a sulfate salt form of colistin, also known as polymyxin E, which was originally discovered in the late 1940s from the bacterium *Bacillus polymyxa* subsp. *colistinus*. The active components of colistin are polymyxin E₁ and polymyxin E₂, cyclic peptides with a fatty acid tail that exhibit potent antibacterial activity through disruption of bacterial cell membranes.

The initial discovery of colistin occurred during the search for new antibiotics in soil-derived microorganisms. As antibiotic resistance began to rise in the mid-20th century, especially among Gram-negative pathogens, the discovery of colistin represented a significant development due to its efficacy against problematic bacteria such as *Pseudomonas aeruginosa*, *Acinetobacter baumannii*, and certain strains of *Klebsiella pneumoniae*. However, due to concerns about nephrotoxicity and neurotoxicity, colistin's use in human medicine declined with the emergence of less toxic alternatives.

Colistin sulfate differs from colistimethate sodium, another pharmaceutical form of colistin, in its pharmacological characteristics and route of administration. While colistimethate sodium is commonly used parenterally for systemic infections, colistin sulfate is more frequently used for oral or topical administration, as well as for gastrointestinal decontamination. Colistin sulfate is poorly absorbed from the gastrointestinal tract, which makes it suitable for treating intestinal infections without significant systemic exposure.

The mechanism of action of colistin sulfate involves interaction with the outer membrane of Gram-negative bacteria. The positively charged amino groups of colistin bind to the negatively charged lipid A component of lipopolysaccharides (LPS) in the bacterial outer membrane. This disrupts membrane integrity by displacing divalent cations such as Mg²⁺ and Ca²⁺ that stabilize LPS. The resulting increased permeability leads to leakage of intracellular contents and ultimately bacterial cell death. This mode of action is specific to Gram-negative organisms, as Gram-positive bacteria lack the outer membrane targeted by colistin.

The reintroduction of colistin into clinical practice began in the early 2000s as multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacterial strains became increasingly prevalent. Colistin sulfate was revisited as a last-resort treatment option for infections that no longer responded to carbapenems and other broad-spectrum antibiotics. Its application is particularly important in treating ventilator-associated pneumonia, bloodstream infections, and complicated urinary tract infections caused by MDR pathogens.

In veterinary medicine, colistin sulfate has been widely used to treat enteric infections in livestock, especially in poultry and swine, due to its effectiveness against *Escherichia coli* and *Salmonella* species. It has also been employed as a growth promoter in animal feed in some countries, although this practice has been restricted or banned in various regions due to concerns about the development and spread of resistance genes.

One of the most significant public health concerns related to colistin sulfate is the emergence of colistin resistance, particularly through plasmid-mediated mechanisms such as the *mcr-1* gene. This gene enables bacteria to modify lipid A with phosphoethanolamine, reducing colistin binding and rendering the bacteria resistant. The discovery of transferable colistin resistance in both clinical and agricultural settings has led to intensified surveillance and regulation of colistin use worldwide.

Pharmacokinetically, colistin sulfate is minimally absorbed when administered orally, with most of the drug excreted unchanged in the feces. When applied topically, it acts locally without substantial systemic exposure. For these reasons, colistin sulfate is often used for decontaminating the digestive tract in immunocompromised patients or as a prophylactic agent in specific surgical procedures.

Despite its clinical utility, colistin sulfate must be used with caution to minimize adverse effects and delay the development of resistance. Proper dosing, therapeutic drug monitoring, and stewardship programs are essential to ensure its continued efficacy in both human and veterinary medicine. The renewed interest in colistin sulfate underlines its importance as a critical option in the antibiotic arsenal, especially in the era of increasing antimicrobial resistance.

References

none