Colistimethate Sodium is an antibiotic prodrug of colistin that has been used in the treatment of severe multidrug-resistant Gram-negative bacterial infections, particularly when other antibiotics are ineffective. Its clinical development and modern use became especially important with the rise of hospital-acquired infections caused by resistant organisms such as Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenem-resistant Enterobacterales. Unlike many older antibiotics, colistimethate sodium regained clinical importance in recent decades due to the global antimicrobial resistance crisis, leading to its reintroduction and increased controlled use in intensive care settings.
BRAND NAMES
Colomycin
Coly-Mycin M
Colistin Injection.
MECHANISM OF ACTION
Colistimethate Sodium is an inactive prodrug that is converted in vivo to colistin (polymyxin E). The active drug acts primarily on the outer membrane of Gram-negative bacteria by binding to lipopolysaccharides (LPS) and phospholipids. This binding displaces calcium and magnesium ions that stabilize the bacterial membrane, leading to disruption of membrane integrity.
PHARMACOKINETICS
Absorption
Colistimethate Sodium is poorly absorbed from the gastrointestinal tract, so it is not effective orally for systemic infections. Therefore, it is administered via parenteral routes (intravenous or intramuscular) for systemic infections, or by inhalation for respiratory tract infections.
Distribution
Colistimethate Sodium has a relatively low to moderate volume of distribution, indicating limited penetration into certain tissues after systemic administration. The drug distributes mainly into extracellular fluid compartments, with good concentrations achieved in serum, kidneys, and lungs (especially with inhaled therapy).
Metabolism
Colistimethate Sodium is an inactive prodrug that undergoes slow non-enzymatic hydrolysis in vivo to form the active compound colistin (polymyxin E). This conversion occurs in plasma and tissues rather than through a specific hepatic enzyme system.
Elimination
Colistimethate Sodium is eliminated primarily through the renal route. A significant portion is excreted in the urine as both the unchanged prodrug and the active form, colistin. Because renal clearance is the main pathway of elimination, drug accumulation can occur in patients with renal impairment, requiring dose adjustment to avoid toxicity.
PHARMACODYNAMICS
Colistimethate Sodium is an inactive prodrug that is converted to colistin, which exerts a rapid, concentration-dependent bactericidal effect against Gram-negative bacteria. The active drug binds to lipopolysaccharides (LPS) and phospholipids in the outer membrane of bacteria, displacing stabilizing calcium and magnesium ions.
ADMINISTRATION
Colistimethate Sodium is administered mainly in hospital settings for severe multidrug-resistant Gram-negative infections. It is given by intravenous (IV) infusion for systemic infections such as sepsis and hospital-acquired pneumonia. In patients with respiratory infections, it may also be administered via inhalation (nebulization) to achieve high local lung concentrations.
DOSAGE AND STRENGTH
Colistimethate Sodium is supplied in vials with strength expressed as international units (IU) or colistin base activity (CBA), depending on the formulation and manufacturer. The dosage varies according to the severity and site of infection, route of administration, and patient renal function.
DRUG INTERACTIONS
Colistimethate Sodium has clinically important interactions mainly related to nephrotoxicity and neurotoxicity. Concomitant use with other nephrotoxic drugs such as aminoglycosides, vancomycin, amphotericin B, or nonsteroidal anti-inflammatory drugs (NSAIDs) can significantly increase the risk of kidney damage.
FOOD INTERACTIONS
Colistimethate Sodium has no clinically significant food interactions, as it is not administered orally for systemic absorption. It is given intravenously or by inhalation, so food does not affect its absorption, distribution, or effectiveness. Patients receiving the drug do not need to follow any specific dietary restrictions related to its use.
CONTRAINDICATIONS
Colistimethate Sodium is contraindicated in patients with a known hypersensitivity to colistimethate sodium, colistin, or other polymyxin antibiotics. It should not be used in individuals with severe myasthenia gravis, as it may worsen neuromuscular blockade and lead to respiratory depression.
SIDE EFFECTS
Nephrotoxicity (most important)
Increased serum creatinine
Acute kidney injury
Reduced urine output.
OVER DOSE
Overdose of Colistimethate Sodium can lead to serious dose-related toxicity, primarily affecting the kidneys and nervous system. The most important manifestations include severe nephrotoxicity, such as acute kidney injury, marked elevation of serum creatinine, oliguria, and possible renal failure.
TOXICITY
Colistimethate Sodium has a narrow therapeutic index, and its toxicity is mainly related to dose-dependent nephrotoxicity and neurotoxicity. Nephrotoxicity is the most significant toxic effect and may present as acute tubular injury, increased serum creatinine, reduced glomerular filtration rate, and in severe cases acute kidney failure.
