Polypeptide Antibiotics

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Chapter: Essential pharmacology : Macrolide, Lincosamide, Glycopeptide And Other Antibacterial Antibiotics; Urinary Antiseptics

These are low molecular weight cationic polypeptide antibiotics. All are powerful bactericidal agents, but not used systemically due to toxicity. All are produced by bacteria.


POLYPEPTIDE ANTIBIOTICS

 

These are low molecular weight cationic polypeptide antibiotics. All are powerful bactericidal agents, but not used systemically due to toxicity. All are produced by bacteria. Clinically used ones are:

 

Polymyxin B       

Bacitracin

Colistin               

Tyrothricin

 

Polymyxin B and Colistin

 

Polymyxin and colistin were obtained in the late 1940s from Bacillus polymyxa and B. colistinus respectively. They are active against gram-negative bacteria only; all except Proteus, Serratia and Neisseria are inhibited. Both have very similar range of activity, but colistin is more potent on Pseudomonas, Salmonella and Shigella.

 

Mechanism Of Action

 

They are rapidly acting bactericidal agents; have a detergent-like action on the cell membrane. They have high affinity for phospholipids: the peptide molecules (or their aggregates) orient between the phospholipid and protein films in gram-negative bacterial cell membrane causing membrane distortion or pseudopore formation. As a result ions, amino acids, etc. leak out. Sensitive bacteria take up more of the antibiotic. They may also inactivate the bacterial endotoxin.

 

They exhibit synergism with many other AMAs by improving their penetration into the bacterial cell.

 

Resistance

 

Resistance to these antibiotics has never been a problem. There is no cross resistance with any other AMA.

 

Adverse Effects

 

Little or no absorption occurs from oral route or even from denuded skin (burn, ulcers). Applied topically, they are safe—no systemic effect or sensitization occurs. A rash is rare.

 

·          Given orally, side effects are limited to the g.i.t.— occasional nausea, vomiting, diarrhoea.

·     Systemic toxicity of these drugs (when injected) is high: flushing and paresthesias (due to liberation of histamine from mast cells), marked kidney damage, neurological disturbances, neuromuscular blockade.

 

Preparation And Dose

 

Polymyxin B: (1 mg = 10,000 U)

 

NEOSPORIN POWDER: 5000 U with neomycin sulf. 3400 U and bacitracin 400 U per g.

 

NEOSPORIN EYE DROPS: 5000 U with neomycin sulf. 1700 U and gramicidin 0.25 mg per ml. NEOSPORINH EAR DROPS: 10,000 U with neomycin sulf. 3400 U and hydrocortisone 10 mg per ml.

 

Colistin sulfate: 25–100 mg TDS oral; WALAMYCIN 12.5 mg (25000 i.u.) per 5 ml dry syr, COLISTOP 12.5 mg/ 5 ml and 25 mg/5 ml dry syr.

 

Uses

 

a)    Topically: Usually in combination with other antimicrobials for skin infections, burns, otitis externa, conjunctivitis, corneal ulcer—caused by gram-negative bacteria including Pseudomonas.

 

b)   Orally: Gram-negative bacillary (E. coli, Salmonella, Shigella) diarrhoeas, especially in infants and children; Pseudomonas superinfection enteritis.

 

Bacitracin

 

It is one of the earliest discovered antibiotics from a strain of Bacillus subtilis. In contrast to polymyxin, it is active mainly against gram-positive organisms (both cocci and bacilli). Neisseria, H. influenzae and few other bacteria are also affected.

 

It acts by inhibiting cell wall synthesis at a step earlier than that inhibited by penicillin. Subsequently, it increases the efflux of ions by binding to cell membrane. It is bactericidal.

 

Bacitracin is not absorbed orally. It is not used parenterally because of high toxicity, especially to the kidney. Use is restricted to topical application for infected wounds, ulcers, eye infections—generally in combination with neomycin, polymyxin, etc.

 

In NEBASULF 250 U/g powder, skin oint, eye oint; in NEOSPORIN 400 U/g powder. (1 U = 26 μg).

 

It does not penetrate intact skin, therefore, of little value in furunculosis, boils, carbuncles, etc.

 

Tyrothricin

 

It is a mixture of gramicidin and tyrocidin, obtained from Bacillus bravis. It is active against gram-positive and a few gram-negative bacteria. It acts on cell membrane causing leakage and uncouples oxidative phosphorylation in the bacteria.

 

Tyrothricin is not absorbed orally and is too toxic for systemic use; causes haemolysis. Used only topically; does not cause sensitization.

TYRODERM: 0.5 mg/g skin cream; PROTHRICIN 0.2 mg/ml topical solution.

 

TYOTOCIN: 0.05% otic solution with benzocaine 1.25% antipyrine 5%, hexylresorcinol 0.1%.

 

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