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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