Polymyxins

Mechanism of action and antimicrobial spectrum

In terms of their structure, polymyxins belong to cationic detergents. Their antibacterial action is implemented in several stages:

1. Direct contact with the phospholipids of the bacterial cell cytoplasmic membrane.
2. Disorganization and disruption of the membrane structure.
3. Sharp increase in cell wall permeability.
4. Mass efflux of potassium and sodium ions and key cytoplasmic components.

The end result of this process is the death of the microbial cell (bactericidal effect). The drugs are highly active against most gram-negative microorganisms. Their spectrum includes Escherichia coli (E. coli), Salmonella, Shigella, Klebsiella, Haemophilus influenzae, and Pseudomonas aeruginosa (P. aeruginosa).

Pharmacokinetics and general principles of use

The main feature of polymyxin pharmacokinetics is that when administered orally, they are practically not absorbed in the gastrointestinal tract, and are also poorly absorbed from mucous membranes and large wounds.

Based on this, the main approaches to their prescribing are formed:

• Topical use: the primary method of use for lesions of the skin, eyes, ears, and mucous membranes.
• Enteral use: prescribed exclusively for intestinal decontamination before surgical interventions or for local effects on the intestinal flora during infections (with no systemic effect).

Features of Polymyxin B and Polymyxin M

Polymyxin B is used depending on the chosen route:

• Orally: for gastrointestinal infections and as a reserve agent when P. aeruginosa is resistant to other antibiotics.
• Topically: in ophthalmology (keratitis, conjunctivitis), ENT practice (otitis externa, sinusitis), and surgery (burns, bedsores, osteomyelitis).
• Parenterally (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 inflammation of the ear or eyes. Orally, it is prescribed for acute and chronic colitis, enterocolitis, dysentery (when other therapy is ineffective), and to prepare the intestines for 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 the appearance of protein in the urine (albuminuria).
• Neurotoxicity: affects the central nervous system (dizziness, drowsiness, ataxia), visual organs, 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 developing respiratory muscle paralysis and apnea.
• Other effects: allergic reactions, dyspepsia (nausea, abdominal pain), local reactions at the injection site (pain, thrombophlebitis), and the risk of superinfection (candidiasis).

Class and exam questions

What else to study on this topic

• Chemical structure of cyclic peptide antibiotics
• History of the discovery of Bacillus polymyxa in 1947
• Detailed mechanism of sodium channel blockade and neuromuscular transmission
• Differential diagnosis of nephrotoxic effects
• Preoperative bowel decontamination using polymyxins

Other topics in the section "Antibacterial Chemotherapeutic Agents"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.