Colistimethate

Summary

Colistimethate sodium (CMS) is a prodrug of colistin used to treat serious infections caused by multidrug-resistant (MDR) Gram-negative bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. It is considered a last-resort antibiotic and can be administered intravenously or by inhalation. Its use is limited by significant nephrotoxicity and neurotoxicity.

Mechanism of Action

Colistimethate is an inactive prodrug that is hydrolyzed in vivo to colistin (polymyxin E). Colistin disrupts the outer membrane of Gram-negative bacteria by competitively displacing divalent cations (Ca2+, Mg2+) from lipopolysaccharide phosphate groups, increasing membrane permeability, leading to leakage of intracellular contents and bacterial death.

Routes of Administration

Goals & Uses

• Combination therapy for XDR infectionsAntimicrobialModerate
• Treatment of MDR Gram-negative infectionsAntimicrobialHigh
• Ventilator-associated pneumonia (VAP) treatmentAntimicrobialModerate
• Pulmonary infection suppression in cystic fibrosisAntimicrobialModerate

Contraindications

• Severe pre-existing renal impairment (if alternatives exist)RenalHigh
• Hypersensitivity to colistin or polymyxinsAllergyHigh
• Myasthenia gravisNeuromuscular DiseaseHigh

Adverse Effects

• NeurotoxicityNeurologicalUncommon
• Injection site reactionsLocalCommon
• Electrolyte disturbancesMetabolicUncommon
• BronchospasmRespiratoryUncommon
• NephrotoxicityRenalCommon
• Superinfection / Clostridium difficileInfectiousUncommon

Drug Interactions

• Non-depolarizing neuromuscular blocking agents (e.g., vecuronium)High
• Aminoglycosides (e.g., gentamicin, tobramycin)High
• VancomycinModerate
• NSAIDsModerateMay increase renal risk in susceptible patients
• Loop diuretics (e.g., furosemide)Moderate

Population Constraints

• Renal impairmentOrgan ImpairmentRelative
• Patients with neuromuscular disordersNeurologicalAbsolute
• Pediatric patientsAgeRelative
• Elderly patientsAgeRelative
• Pregnancy (Category C/D)PregnancyRelative

Regulatory Status

• European UnionApprovedApproved: Infections caused by aerobic Gram-negative bacteria in adults and pediatric patients including cystic fibrosis, Inhaled use for chronic pulmonary Pseudomonas aeruginosa infections in cystic fibrosisEMA updated guidelines in 2014 recommending dosing in million international units (MIU); multiple approved brand names including Colobreathe (inhaled)
• United StatesApprovedApproved: Acute or chronic infections due to sensitive strains of Gram-negative bacilli, particularly Pseudomonas aeruginosaFDA-approved; Coly-Mycin M Parenteral; off-label use for MDR pathogens is common; TDM recommended
• United KingdomApprovedApproved: Serious infections due to susceptible Gram-negative organisms, Suppressive therapy of chronic pulmonary Pseudomonas aeruginosa infection in cystic fibrosisMHRA approved; available as Colomycin injection and Colobreathe inhalation powder; NICE guidelines support use in CF

Approved in the US (FDA) and EU (EMA) for serious Gram-negative infections. EMA issued updated guidelines on dosing in 2014. Therapeutic drug monitoring (TDM) is recommended due to narrow therapeutic index.

Evidence & Sources

No sources recorded yet.