Mechanism of Action and Antimicrobial Spectrum
Structurally, polymyxins are classified as cationic detergents. Their antibacterial action unfolds in several stages:
- Direct contact with phospholipids of the bacterial cytoplasmic membrane.
- Disorganization and disruption of the membrane structure.
- Sharp increase in cell wall permeability.
- Massive leakage of potassium and sodium ions, as well as key cytoplasmic components.
The end result of this process is the death of the microbial cell (bactericidal effect). These drugs are highly active against most gram-negative microorganisms. Their spectrum includes Escherichia coli, Salmonella, Shigella, Klebsiella, Haemophilus influenzae, and Pseudomonas aeruginosa.
Pharmacokinetics and General Principles of Use
A major pharmacokinetic feature of polymyxins is that when administered orally, they are practically unabsorbed in the gastrointestinal tract and are also poorly absorbed from mucous membranes and large wounds.
Based on this, the main approaches to their administration are:
- Topical administration: The primary method for skin, eye, ear, and mucosal lesions.
- Enteral administration: Prescribed exclusively for bowel decontamination prior to surgical interventions or for localized effects on intestinal flora during infections (without systemic effects).
Characteristics of Polymyxin B and Polymyxin M
Polymyxin B is used depending on the chosen route:
- Oral: For GI infections and as a reserve agent when P. aeruginosa is resistant to other antibiotics.
- Topical: In ophthalmology (keratitis, conjunctivitis), ENT practice (otitis externa, sinusitis), and surgery (burns, pressure ulcers, osteomyelitis).
- Parenteral (IV, IM): For severe generalized infections (sepsis, meningitis, lung abscess, pneumonia).
- Polymyxin M is available as a solution and liniment. It is used topically to treat non-healing wounds, ulcers, burns, and ear or eye inflammation. Orally, it is prescribed for acute and chronic colitis, enterocolitis, dysentery (when other therapy fails), and for bowel preparation before surgery.
Side Effects and Toxicity
With systemic and improper use, polymyxins can cause serious adverse reactions:
- Nephrotoxicity: Manifests as an increase in blood urea nitrogen (azotemia) and proteinuria.
- Neurotoxicity: Affects the central nervous system (dizziness, drowsiness, ataxia), vision, and the peripheral nervous system in the form of paresthesias.
- Neuromuscular blockade: Due to the blockade of sodium channels, there is a real risk of respiratory muscle paralysis and apnea.
- Other effects: Allergic reactions, dyspepsia (nausea, abdominal pain), injection site reactions (pain, thrombophlebitis), and the risk of superinfection (candidiasis).