• Wednesday April 8,2020

colistin

Colistin is a drug from the group of antibiotics. The polypeptide antibiotic interferes with the permeability of the cell membrane of the bacteria and thus kills them.

What is Colistin?

Colistin is a drug from the group of antibiotics. The active ingredient can be used locally as an ointment or as an aerosol in inhalation therapy.

Colistin is a drug with a high toxicity. He was therefore long time mainly used locally as an ointment or as an aerosol in the inhalation therapy. Especially in people with cystic fibrosis who suffered from Pseudomonas colonization, colistin was used.

Systemic administration was avoided for a long time due to the kidney-damaging activity of the drug. Meanwhile, the antibiotic is also systemically prescribed again more often. This is due to the increased occurrence of enterobacteria that are resistant to the antibiotics from the drug group of carbapenems. CRE (carbapenem-resistant enterobacteria) are found mainly in the USA, Israel, Turkey, Greece and North African countries. CRE can often only be treated with colistin, fosfomycin and tigecycline.

Colistin is also known as Polymixin E. It belongs to the group of polymyxins and has been used therapeutically since 1959. Polymyxins are polypeptide antibiotics that consist of chemically branched, cyclic decapeptides.

Pharmacological action

Colistin, or colistimethate sodium (CMS), is a prodrug. Prodrugs are inactive or only slightly pharmacologically active substances, which are converted into an active substance only after the metabolism in the organism. This process is also called metabolization. The prodrug becomes the metabolite. The prodrug concept is intended to improve the pharmacokinetic substance property of the drug. Pro-drugs often improve bioavailability and reduce the first-pass effect.

Colistin is administered parenterally, bypassing the gastrointestinal tract. After parenteral administration, the inactive drug colistimethate sodium is converted to the active colistin base by the chemical process of hydrolysis. This is pharmacologically active. The result is 80 milligrams of CMS about 33 milligrams of colistin bases.

Colistin ensures increased permeability on the cell walls of the bacteria. As a result, various substances can penetrate into the bacterial cell. The osmolarity is disturbed and eventually the bacterial cells burst.

Since gram-positive bacteria, in contrast to the gram-negative bacteria, have no outer cell membrane, colistin only works in gram-negative bacteria. Sensitive to colistin are Shigella, Salmonella, Haemophilus influenzae, Acinetobacter and Pasteurella. Klebsiella, Escherichia coli, Enterobacter and Pseudomonas aeruginosa are also sensitive to the antibiotic. Proteus, gonococci, gram-positive bacteria and meningococci, on the other hand, are resistant.

Medical application & use

Colistin is used today only after careful risk-benefit assessment. One indication is patients with cystic fibrosis who are infected with Pseudomonas aeruginosa. Cystic fibrosis is a hereditary disease associated with the production of viscous secretions by the exocrine glands. Those affected suffer from chronic airway inflammation and gastrointestinal complaints. Pseudomonas aeruginosa causes pneumonia in patients with a suppressed immune system and compromised respiratory tract. These pneumonia are particularly common in cystic fibrosis patients or in intensive care patients.

In addition, Colistin is used to treat infections with the multidrug-resistant bacterium Acinetobacter baumannii. Acinetobacter baumanii is a human pathogenic short-rod bacterium of the Moraxellaceae family. The germ causes worldwide nosocomial infections. Nosocomial infections are infections that are causally related to hospital stays. Infections with Acinetobacter baumanii are mainly observed in respiratory patients in the intensive care sector. The infection usually results in nosocomial pneumonia. Urinary tract infections, wound infections and blood poisoning are also caused by the resistant pathogen.

Risks & Side Effects

Taking colistin may cause adverse effects. Frequently, allergic skin reactions or contact dermatitis appear. Also allergic asthma attacks are observed in response to colistin.

The antibiotic is also nephrotoxic. So it has a damaging effect on the kidneys. It can come to an acute necrosis of the small Urnkanälchen in the kidney. This usually leads to acute renal failure within a short time. The kidney can no longer fulfill its filtration task, so that more and more urinary substances accumulate in the blood.

Colistin is not only nephro- but also neurotoxic. Possible symptoms of nervous system damage include dizziness, convulsions, coma, blurred vision or speech disorders. Blood damage can also be caused by the antibiotic.

Due to its nephrotoxic effects, colistin should not be used in patients with renal insufficiency. Severe heart-related excretory disorders also constitute a contraindication. Hypersensitivity to the active substance colistin or to other polymyxins is also an exclusion criterion. Due to the serious potential side effects for the unborn or newborn, colistin should not be given during pregnancy and while breast-feeding.

It should be noted that the side effects increase when combined with nephrotoxic drugs. Such nephrotoxic drugs include vancomycin, loop diuretics and aminoglycosides. Also, neuromuscular blocking agents, such as muscle relaxants, may increase the side effects of colistin.

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