Colistin
Also known as: CMS, Colistimethate sodium, Colistin sulfate, Colomycin, Coly-Mycin, Coly-Mycin M, Polymyxin E
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Summary
Colistin (polymyxin E) is a cyclic lipopeptide antibiotic approved for prescription use as a last‑line treatment against serious infections caused by multidrug‑resistant Gram‑negative bacteria. It is employed when other agents, including carbapenems, fail, and is administered by intravenous, intramuscular, inhalation, oral or topical routes. Growing worldwide resistance, especially plasmid‑borne mcr genes, has raised concerns about its continued efficacy.
Mechanism of Action
Colistin binds to the lipid A component of lipopolysaccharide in the outer membrane of Gram‑negative organisms, displacing stabilising calcium and magnesium ions. This interaction disrupts membrane integrity, increases permeability and leads to rapid bacterial cell lysis. Resistance mechanisms—such as mcr‑mediated modification of lipid A—reduce this binding and restore membrane stability.
What the Research Shows
Recent literature confirms colistin’s role as a last‑resort drug for multidrug‑resistant Gram‑negative infections, but highlights the rapid spread of plasmid‑mediated mcr resistance genes (Liu et al., 2024). In vitro synergy studies show that colistin combined with rifampicin (against Acinetobacter baumannii) or fosfomycin (against Klebsiella pneumoniae) yields high or moderate synergistic effects and reduces bacterial regrowth compared with monotherapy (Scudeller et al., 2021). Clinical network meta‑analyses indicate that colistin‑based combinations improve microbiological outcomes but are linked to a higher risk of nephrotoxicity (Liu et al., 2021). The ATTACK phase‑3 trial demonstrated that colistin, given with imipenem‑cilastatin, had similar 28‑day mortality to sulbactam‑durlobactam but caused substantially more nephrotoxicity (Kaye et al., 2023). Collectively, these data underscore colistin’s potency, the promise of synergistic regimens, and the safety challenges that limit its use.
Reported Benefits
Colistin retains activity against a broad range of carbapenem‑resistant Gram‑negative pathogens, making it a vital option when other agents fail. In vitro studies show that combining colistin with rifampicin or fosfomycin can enhance bactericidal activity and limit regrowth, potentially improving clinical outcomes for infections such as Acinetobacter baumannii and Klebsiella pneumoniae. Its availability in multiple formulations permits use in systemic and respiratory infections.
Limitations of the Evidence
The emergence and global dissemination of mcr‑mediated colistin resistance diminish its reliability as a last‑line agent. Nephrotoxicity is a frequent and dose‑limiting adverse effect, reported at higher rates than newer alternatives in clinical trials. Evidence for optimal combination regimens remains confined to in vitro models, and robust clinical data are limited, highlighting the need for further trials and antimicrobial stewardship.
Safety Considerations
Nephrotoxicity is the most prominent safety concern, with clinical trials reporting up to 38 % incidence in colistin‑treated patients versus 13 % for comparator regimens. Renal impairment may be dose‑related and can necessitate therapy discontinuation. Although not detailed in the cited abstracts, neurotoxicity has also been associated with polymyxin use, underscoring the need for careful monitoring of renal function and neurologic status during treatment.
How It Is Administered
Colistin is supplied as colistimethate sodium for intravenous or intramuscular injection and as inhalation formulations for respiratory infections. Oral and topical preparations are also available for specific indications. Dosing varies with indication, renal function and formulation; clinicians select the route that best reaches the infection site while balancing toxicity risk.
Routes of Administration
Goals & Uses
- Intestinal decontaminationAntimicrobialLow
- Treatment of carbapenem-resistant Klebsiella pneumoniae infectionsAntimicrobialModerate
- Inhalation therapy for pulmonary infections in cystic fibrosisAntimicrobialModerate
- Treatment of carbapenem-resistant Acinetobacter baumannii infectionsAntimicrobialModerate
- Treat multidrug‑resistant Gram‑negative infectionsAntibacterialHigh
- Treatment of multidrug-resistant Pseudomonas aeruginosa infectionsAntimicrobialModerate
Contraindications
- Severe renal impairment (eGFR <30 mL/min/1.73 m²)RenalModerate
- Hypersensitivity to colistin or polymyxinsAllergyHigh
- Severe pre-existing renal impairment (without dose adjustment)RenalHigh
- Known hypersensitivity to colistin or polymyxinsAllergyHigh
- Myasthenia gravisNeuromuscular DiseaseHigh
Adverse Effects
- NeurotoxicityNeurologicalUncommon
- Injection site reactionsLocalCommon
- OtotoxicityAuditory/vestibularRare
- Electrolyte disturbancesMetabolicUncommon
- BronchospasmRespiratoryUncommon
- Apnea / respiratory failureRespiratoryRare
- NephrotoxicityRenalCommon
Drug Interactions
- AminoglycosidesHigh
- Neuromuscular blocking agents (e.g., vecuronium)Moderate
- Non-depolarizing neuromuscular blocking agentsHigh
- VancomycinModerate
- NSAIDsModerateMay increase renal risk in susceptible patients
- Loop diuretics (e.g., furosemide)Moderate
Population Constraints
- PregnancyReproductive SafetyRelative
- Renal impairmentOrgan ImpairmentRelative
- Pediatric patients (<18 y)AgeRelative
- Elderly patientsAgeRelative
- Neonates and premature infantsPediatricRelative
- Pregnant womenReproductiveRelative
Regulatory Status
- European UnionApprovedApproved: Severe infections due to multidrug‑resistant Gram‑negative bacteriaApproved for IV use; inhaled colistin authorized in some member states for cystic fibrosis.
- United StatesApprovedApproved: Complicated urinary tract infections, Ventilator‑associated pneumonia, Bloodstream infections caused by susceptible Gram‑negative organismsIV formulation approved; inhalation use is off‑label.
- United KingdomApprovedApproved: Serious infections due to susceptible Gram-negative organisms, Chronic pulmonary infections in cystic fibrosis (inhaled)MHRA-approved. Listed as a reserve antibiotic; use guided by antimicrobial stewardship programs.
Limited to severe infections due to significant nephro‑ and neuro‑toxicity; dosing requires renal function monitoring.
Evidence & Sources
- Journal ArticleModerateLiu JH, et al.2024-01-01T00:00:00.000000Z
- Journal ArticleHighScudeller L, et al.2021-01-01T00:00:00.000000Z
- Journal ArticleHighLiu J, et al.2021-01-01T00:00:00.000000Z
- Journal ArticleModerateEl-Sayed Ahmed MAE, et al.2020-01-01T00:00:00.000000Z
- Journal ArticleModerateMondal AH, et al.2024-01-01T00:00:00.000000Z
- Journal ArticleModerateKaye KS, et al.2023-01-01T00:00:00.000000Z
Frequently Asked Questions
When is colistin typically used in clinical practice?
Colistin is reserved for infections caused by multidrug‑resistant Gram‑negative bacteria, especially when carbapenems and other agents are ineffective. It is often employed for severe bloodstream, pneumonia or urinary tract infections caused by organisms such as Acinetobacter baumannii, Pseudomonas aeruginosa or Klebsiella pneumoniae.
How does bacterial resistance to colistin develop?
Resistance commonly arises through acquisition of plasmid‑borne mcr genes that modify lipid A, reducing colistin binding. Chromosomal mutations that alter LPS structure or increase efflux can also confer resistance, limiting the drug’s efficacy.
Can colistin be combined with other antibiotics to improve outcomes?
In vitro studies report synergistic activity when colistin is paired with rifampicin or fosfomycin, leading to greater bacterial killing and less regrowth. Clinical data suggest combination therapy may enhance efficacy, but it also raises the risk of nephrotoxicity.
What monitoring is required during colistin therapy?
Renal function should be monitored closely, with serum creatinine and estimated glomerular filtration rate checked regularly. Neurologic assessment is advised, as neurotoxic effects have been reported with polymyxins.
Is colistin approved for inhalation use?
Yes, inhaled colistimethate sodium formulations are approved for delivering the drug directly to the lungs, primarily for treating ventilator‑associated or other respiratory infections caused by susceptible Gram‑negative pathogens.
What is Colistin?
Colistin (polymyxin E) is a cyclic lipopeptide antibiotic approved for prescription use as a last‑line treatment against serious infections caused by multidrug‑resistant Gram‑negative bacteria. It is employed when other agents, including carbapenems, fail, and is administered by intravenous, intramuscular, inhalation, oral or topical routes. Growing worldwide resistance, especially plasmid‑borne mcr genes, has raised concerns about its continued efficacy.
What is Colistin used for?
Colistin is educationally associated with: Intestinal decontamination, Treatment of carbapenem-resistant Klebsiella pneumoniae infections, Inhalation therapy for pulmonary infections in cystic fibrosis, Treatment of carbapenem-resistant Acinetobacter baumannii infections, Treat multidrug‑resistant Gram‑negative infections, Treatment of multidrug-resistant Pseudomonas aeruginosa infections. Educational only — not medical advice.
How is Colistin administered?
Recorded routes of administration: Inhalation, Intramuscular, Intravenous, Oral, Topical.
What are the potential side effects of Colistin?
Reported adverse effects include: Neurotoxicity, Injection site reactions, Ototoxicity, Electrolyte disturbances, Bronchospasm, Apnea / respiratory failure, Nephrotoxicity. This list is not exhaustive — consult a qualified clinician.
Who should avoid Colistin?
Recorded contraindications: Severe renal impairment (eGFR <30 mL/min/1.73 m²), Hypersensitivity to colistin or polymyxins, Severe pre-existing renal impairment (without dose adjustment), Known hypersensitivity to colistin or polymyxins, Myasthenia gravis. Consult a qualified clinician before use.