Coly-Mycin M, Colistimethate
Evidence Grade A — Regulatory approved. 12107 published studies. 118 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.
12,107 published studies: 6272 human, 1376 animal, 1781 in-vitro, 961 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.
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
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
The Effect of Adjunctive Melatonin With Colistin in Patients With Multidrug-Resistant Gram-Negative Bacterial Infections
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