Polymyxin antibiotics : Classification, Mechanism of action, Clinical uses, Indications, Dosage, Side Effects, Warnings, Interactions, Precautions, Contraindications & Brand names
- Polymyxin antibiotics are low molecular weight cationic polypeptide antibiotics.
- Polymyxin B
- Colistin (Polymyxin E)
Mechanism of action
Polymyxins have high affinity for phospholipids. They have detergent-like action on the cell membrane & bind to phospholipids on the bacterial cell membrane of gram-negative bacteria causing membrane distortion or pseudopore formation i.e. disrupts cell membrane integrity. It leads to leakage of cellular components (ions, amino acids, etc.) & ultimately cell death.
Sensitive bacteria take up more of the antibiotic. Polymyxins may also inactivate the bacterial endotoxin. They exhibit synergism with many other AMAs by improving their penetration into the bacterial cell.
Polymyxins are active against gram-negative bacteria only. They are active against most clinically important gram-negative bacteria except Proteus, Serratia and Neisseria. Thay are rapidly acting concentration-dependent bactericidal agents. Both have very similar range of activity, but colistin is more potent on Pseudomonas, Salmonella and Shigella.
Polymyxins have following uses :
- Topically : Usually in combination with other antimicrobials for skin infections, burns, otitis externa, conjunctivitis, corneal ulcer-caused by gram-negative bacteria including Pseudomonas.
- Orally : Gram-negative bacillary (E. coli, Salmonella Shigella) diarrhoeas, especially in infants and children, Pseudomonas superinfection enteritis.
Typical uses are for infections caused by strains of multiple drug-resistant Pseudomonas aeruginosa or carbapenemase-producing Enterobacteriaceae.
Resistance to polymyxins has never been a problem. There is no cross resistance with any other AMA. However, alterations in the cell membrane lipid polysaccharides allow many species of Proteus and Serratia to be intrinsically resistant.
The use of polymyxins drugs has been limited for a long time, due to the increased risk of nephrotoxicity and neurotoxicity (for example, slurred speech, muscle weakness) when used systemically. However, with the increase in gram-negative resistance, they have seen a resurgence in use and are now commonly used as salvage therapy for patients with multidrug-resistant infections. Careful dosing and monitoring of adverse effects are important to maximize the safety and efficacy of these agents.
- Applied topically, they are safe-no systemic effect or sensitization occurs. A rash is rare.
- When given orally, polymyxin B may cause occasional nausea, vomiting, diarrhoea.
- When injected, polymyxin B may cause high toxicity such as flushing and paresthesias (due to liberation of histamine from mast cells), marked kidney damage, neurological disturbances, neuromuscular blockade.
- Contraindicated in persons having hypersensitivity to any of drug.
For detailed query or in case of uncertainty, Always consult your doctor or pharmacist.