Colistimethate
Also known as: CMS, Colistimethate sodium, Colistin, Colistin methanesulfonate, Colistin methanesulfonate sodium, Coly-Myc, Coly-Mycin M, Polymyxin E methanesulfonate
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Summary
Colistimethate sodium (CMS) is a prescription prodrug of the polymyxin antibiotic colistin. It is used to treat severe infections caused by multidrug‑resistant Gram‑negative bacteria such as Acinetobacter baumannii and Pseudomonas aeruginosa, and is administered intravenously, intramuscularly, or by inhalation for respiratory disease.
Mechanism of Action
CMS is an inactive sulphate salt that is hydrolysed in the body to the active lipo‑peptide colistin. Colistin binds to the lipid A component of lipopolysaccharide in the outer membrane of Gram‑negative bacteria, displacing stabilising cations, increasing membrane permeability and causing rapid cell lysis.
What the Research Shows
Clinical reviews note that systemic polymyxins cause dose‑dependent nephrotoxicity in roughly 30‑60% of patients, limiting their use. Pharmacokinetic studies in animals highlight the need for accurate analytical methods because CMS converts to colistin during sample handling, affecting measured concentrations and tissue distribution, especially in the kidneys. In intensive‑care settings, colistin (administered as CMS) remains one of the few agents active against carbapenem‑resistant Acinetobacter baumannii, with recommended loading and high‑dose maintenance regimens, although combination therapy has not shown mortality benefit. Recent phase‑3 trials of inhaled CMS for bronchiectasis patients colonised with Pseudomonas aeruginosa produced mixed results: PROMIS‑I showed a 39% reduction in annual exacerbations, while PROMIS‑II, halted early by the pandemic, found no difference.
Reported Benefits
CMS provides an option for infections caused by bacteria that are resistant to most other antibiotics, particularly multidrug‑resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Inhaled CMS has demonstrated a clinically meaningful reduction in exacerbation frequency in one large bronchiectasis trial, suggesting benefit for chronic lung infections. Its broad‑spectrum activity against Gram‑negative pathogens makes it a valuable last‑line agent when alternatives are unavailable.
Limitations of the Evidence
Systemic use is constrained by a high incidence of nephrotoxicity, with risk increasing at higher doses and serum concentrations. Pharmacokinetic data are limited and complicated by conversion of CMS to colistin during sampling, leading to uncertainty about optimal dosing. Evidence for combination therapy is inconclusive, and inhaled CMS results are inconsistent across trials. Overall, clinical data are derived from a modest number of studies, and long‑term safety, especially for chronic inhalation, remains incompletely characterised.
Safety Considerations
Nephrotoxicity is the most common serious adverse effect of systemic CMS, occurring in 30‑60% of treated patients and often limiting therapy. Other less frequent toxicities have been reported but are not detailed in the cited literature. In the PROMIS inhalation trials, overall adverse‑event rates were similar between CMS and placebo, and no treatment‑related deaths occurred. Caution is advised in patients with pre‑existing renal impairment, and renal function should be monitored during systemic therapy.
How It Is Administered
CMS is supplied for intravenous, intramuscular, and inhalation routes. The inhaled formulation is delivered via nebulisation, commonly using the I‑neb adaptive aerosol delivery system. When given intravenously, CMS is administered as a loading dose followed by high‑dose, extended‑interval maintenance regimens, as described in clinical reviews. The prodrug is converted in vivo to active colistin.
Routes of Administration
Goals & Uses
- Combination therapy for XDR infectionsAntimicrobialModerate
- Manage chronic Pseudomonas lung infection in cystic fibrosisAntibacterialHigh
- Treatment of MDR Gram-negative infectionsAntimicrobialHigh
- Ventilator-associated pneumonia (VAP) treatmentAntimicrobialModerate
- Pulmonary infection suppression in cystic fibrosisAntimicrobialModerate
- Treat multidrug‑resistant Gram‑negative infectionsAntibacterialHigh
Contraindications
- Severe pre-existing renal impairment (if alternatives exist)RenalHigh
- Hypersensitivity to colistin or polymyxinsAllergyHigh
- Severe renal impairment (creatinine clearance <30 mL/min) without dose adjustmentRenalModerate
- Hypersensitivity to colistin or other polymyxinsAllergyHigh
- Myasthenia gravisNeuromuscular DiseaseHigh
Adverse Effects
- NeurotoxicityNeurologicalCommon
- Injection site reactionsLocalCommon
- OtotoxicityAuditory/vestibularUncommon
- Electrolyte disturbancesMetabolicUncommon
- BronchospasmRespiratoryUncommon
- Neuromuscular blockadeNeuromuscularRare
- NephrotoxicityRenalCommon
- Superinfection / Clostridium difficileInfectiousUncommon
Drug Interactions
- Non‑steroidal anti‑inflammatory drugs (NSAIDs)Moderate
- AminoglycosidesModerate
- Neuromuscular blocking agents (e.g., vecuronium)High
- 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
- PregnancyReproductive SafetyRelative
- Renal impairmentOrgan ImpairmentRelative
- Pediatrics (<1 month)AgeRelative
- Patients with neuromuscular disordersNeurologicalAbsolute
- Pediatric patientsAgeRelative
- Elderly patientsAgeRelative
- Pregnancy (Category C/D)PregnancyRelative
Regulatory Status
- European UnionApprovedApproved: Infections due to susceptible MDR Gram‑negative bacteriaEMA approval with similar restrictions.
- United StatesApprovedApproved: Complicated urinary tract infections, Ventilator‑associated pneumonia, Bloodstream infections caused by MDR Gram‑negative bacteriaColistimethate sodium approved under FDA for limited indications; restricted use program.
- 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
Limited to severe infections due to high nephro‑ and neurotoxicity; dosing requires renal function monitoring; contraindicated in patients with known hypersensitivity to polymyxins.
Evidence & Sources
- Journal ArticleModeratePogue JM, Tam VH2019-01-01T00:00:00.000000Z
- Journal ArticleModerateMarchand S, Grégoire N, Couet W2019-01-01T00:00:00.000000Z
- Journal ArticleModerateGarnacho-Montero J, Timsit JF2019-01-01T00:00:00.000000Z
- Journal ArticleModerateMilne RW2019-01-01T00:00:00.000000Z
- Journal ArticleModerateHaworth CS, et al.2024-01-01T00:00:00.000000Z
Frequently Asked Questions
What types of infections is colistimethate used for?
It is employed for severe infections caused by multidrug‑resistant Gram‑negative bacteria, especially carbapenem‑resistant Acinetobacter baumannii and Pseudomonas aeruginosa, and for chronic lung infections such as bronchiectasis where P. aeruginosa colonisation is present.
Why is kidney toxicity a concern with systemic colistimethate?
Clinical data indicate that 30‑60% of patients receiving systemic polymyxins develop nephrotoxicity, with risk rising alongside higher doses and serum concentrations. The kidneys are a primary site of drug accumulation, leading to functional impairment.
Is inhaled colistimethate effective for bronchiectasis?
One phase‑3 trial (PROMIS‑I) showed a 39% reduction in annual exacerbations, suggesting benefit, whereas a second trial (PROMIS‑II) stopped early due to the pandemic did not demonstrate a difference. Overall, evidence is promising but not definitive.
How is colistimethate measured in the body?
Modern studies use high‑performance liquid chromatography or mass spectrometry to specifically quantify CMS and its conversion product colistin, avoiding the over‑estimation seen with older microbiological methods.
Can colistimethate be combined with other antibiotics?
Combination therapy is frequently used in practice to improve bacterial eradication, but current reviews note that no clinical trials have shown a mortality or length‑of‑stay advantage over monotherapy.
What is Colistimethate?
Colistimethate sodium (CMS) is a prescription prodrug of the polymyxin antibiotic colistin. It is used to treat severe infections caused by multidrug‑resistant Gram‑negative bacteria such as Acinetobacter baumannii and Pseudomonas aeruginosa, and is administered intravenously, intramuscularly, or by inhalation for respiratory disease.
What is Colistimethate used for?
Colistimethate is educationally associated with: Combination therapy for XDR infections, Manage chronic Pseudomonas lung infection in cystic fibrosis, Treatment of MDR Gram-negative infections, Ventilator-associated pneumonia (VAP) treatment, Pulmonary infection suppression in cystic fibrosis, Treat multidrug‑resistant Gram‑negative infections. Educational only — not medical advice.
How is Colistimethate administered?
Recorded routes of administration: Inhalation, Intramuscular, Intrathecal, Intravenous.
What are the potential side effects of Colistimethate?
Reported adverse effects include: Neurotoxicity, Injection site reactions, Ototoxicity, Electrolyte disturbances, Bronchospasm, Neuromuscular blockade, Nephrotoxicity, Superinfection / Clostridium difficile. This list is not exhaustive — consult a qualified clinician.
Who should avoid Colistimethate?
Recorded contraindications: Severe pre-existing renal impairment (if alternatives exist), Hypersensitivity to colistin or polymyxins, Severe renal impairment (creatinine clearance <30 mL/min) without dose adjustment, Hypersensitivity to colistin or other polymyxins, Myasthenia gravis. Consult a qualified clinician before use.