Evidence Grade A — Regulatory approved. 12264 published studies. 119 registered clinical trials.
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Colistin (also called polymyxin E) is an antibiotic of last resort, used when bacteria have become resistant to virtually every other available drug. Originally approved in 1959 and then largely abandoned due to serious kidney toxicity, it was brought back into service in the 2000s as multidrug-resistant infections became a global crisis. Its use is driven entirely by necessity when no other options remain.
Colistin is also known by these brand and alternate names:
12,264 published studies: 6321 human, 1390 animal, 1798 in-vitro, 976 reviews
Colistin is marketed as Coly-Mycin M (approved approximately 1959). It is administered intravenously as the prodrug colistimethate sodium. Colistin also has a role as inhaled therapy for respiratory infections in cystic fibrosis and ventilator-associated pneumonia.
The major limitation is nephrotoxicity — kidney injury occurs in 30–60% of patients receiving intravenous colistin. Clinical trials (AIDA, OVERCOME) have examined combination strategies but have not found that adding a second antibiotic improves outcomes over colistin alone. The emergence of the mcr-1 gene conferring transferable colistin resistance was declared a global public health emergency, as it threatens the effectiveness of this antibiotic of last resort. Colistin use is driven purely by necessity when no other options remain.
Colistin carries a strong positive electrical charge that is attracted to the negatively charged outer membrane of gram-negative bacteria. It binds to a component called lipid A in the bacterial outer membrane, displacing the calcium and magnesium ions that hold the membrane together. The drug's fatty acid tail then inserts into the membrane, creating holes that cause the cell contents to leak out, killing the bacterium. This detergent-like mechanism also neutralises bacterial endotoxin, which can cause septic shock.
Colistin's evidence base is unusual — it was approved decades before modern trial standards, and much of the clinical data comes from observational studies of critically ill patients. Kidney injury occurs in roughly 30-60% of patients receiving intravenous colistin, which is why it is reserved for infections that are resistant to everything else. Clinical trials have examined whether adding a second antibiotic improves outcomes, but results have generally not supported combination therapy over colistin alone. The biggest concern beyond toxicity is resistance. The discovery in 2015 of a transferable resistance gene (mcr-1) that can spread between bacteria was treated as a global public health emergency, because it threatens the effectiveness of this antibiotic of absolute last resort. Several next-generation polymyxin antibiotics designed to be less toxic are currently in early clinical trials.
PeptideTrace tracks 119 registered clinical trials for Colistin sourced from ClinicalTrials.gov.
Microbiologic Effect of Selective Decontamination of the Digestive Tract With Colistin, Gentamicin and Nystatin
Nebulised Colistimethate Sodium to Prevent Pediatric Ventilator-associated Pneumonia
Phenotypic and Genotypic Detection of Colistin Resistance
Comparing Efficacy and Safety of (Meropenem + Colistin) Versus (Imipenem/Cilastatin + Tigecycline) on Eradication of Multi-Drug Resistance Bacteria
Study on the Safety and Efficacy of Polymyxin E2 Methanesulfonate for Injection in the Treatment of Hospital-Acquired Bacterial Pneumonia/Ventilator-Associated Bacterial Pneumonia Caused by Carbapenem-Resistant Gram-Negative Bacteria
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Colistin (polymyxin E) is a cyclic lipopeptide decapeptide (10 AA) from Paenibacillus polymyxa. MW ~1,169 Da (colistin A). Administered as prodrug colistimethate sodium (CMS). Cyclic heptapeptide ring plus linear tripeptide, five Dab residues (+5 charge), N-terminal 6-methyloctanoic acid, D-Leucine at position 6. CMS half-life 2-3h; formed colistin ~4h. IV 2.5-5 mg/kg/day.
Cationic Dab residues bind lipid A phosphate groups on gram-negative outer membrane LPS, displacing Ca2+/Mg2+. Hydrophobic chain inserts into lipid bilayer creating pore-like disruptions, then disrupts inner membrane causing cytoplasmic leakage and osmotic lysis. Additional: endotoxin neutralization, type II NADH-quinone oxidoreductase inhibition, hydroxyl radical generation via Fenton reaction.
Marketed as Coly-Mycin M (CMS injection; approved ~1959). AIDA Trial (Lancet ID 2018; N=406): colistin vs. colistin + meropenem, no difference (28-day CRAB mortality 46% vs. 52%). OVERCOME (N=467): no benefit adding meropenem (mortality 43% vs. 37%). Indications: susceptible gram-negative infections (P. aeruginosa, E. coli, Klebsiella). Widely used off-label for MDR/XDR infections.
Vancomycin is marketed as Vancocin and Firvanq (approved 1958, with oral solution Firvanq approved 2018). It is the standard treatment for serious MRSA infections (bloodstream infections, endocarditis, pneumonia, bone infections) and is first-line for severe C. difficile colitis. Vancomycin requires therapeutic drug monitoring — blood levels must be checked regularly to ensure the dose is effective without causing kidney damage or hearing loss. The rise of vancomycin-resistant enterococci (VRE) and occasional vancomycin-intermediate S. aureus (VISA) strains represent ongoing challenges. Despite being nearly 70 years old, vancomycin remains irreplaceable for many serious infections, though newer alternatives like daptomycin and the lipoglycopeptides offer advantages in specific settings.
Zilucoplan is marketed as Zilbrysq (approved October 2023) for anti-acetylcholine receptor antibody-positive generalised myasthenia gravis in adults. Administered as a daily subcutaneous self-injection. In the RAISE trial, zilucoplan showed statistically significant improvements in both activities of daily living and quantitative muscle strength scores compared to placebo, with improvements evident from week one. Its key differentiator from existing complement inhibitors (eculizumab, ravulizumab) is the self-injectable format — those alternatives require hospital-based intravenous infusions. As with all complement inhibitors, patients require meningococcal vaccination before starting treatment due to increased susceptibility to meningococcal infection.
Daptomycin is marketed as Cubicin (approved September 2003). It is indicated for complicated skin and soft tissue infections and S. aureus bloodstream infections including right-sided endocarditis. Administered as a once-daily intravenous infusion. A key limitation is that daptomycin cannot be used for pneumonia — lung surfactant inactivates the drug. In the bacteraemia trial, daptomycin was non-inferior to vancomycin with significantly lower rates of kidney problems (11% versus 26%). Creatine kinase (CK) levels must be monitored during treatment, as daptomycin can cause muscle toxicity. Generics became available after patent expiry, significantly reducing cost.
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