Colistin is a drug from the group of antibiotics. The polypeptide antibiotic disrupts the permeability of the cell membrane of bacteria, thus killing them.
What is colistin?
Colistin is a drug from the group of antibiotics. The active ingredient can be used locally as an ointment additive or as an aerosol in inhalation therapy. Colistin is a drug with a high toxicity. For a long time, it was therefore mainly used locally as an ointment additive or as an aerosol in inhalation therapy. In particular, colistin was used in people with cystic fibrosis who suffered from Pseudomonas colonization. Systemic administration was avoided for a long time because of the drug’s kidney-damaging effects. In the meantime, the antibiotic is again being prescribed more frequently systemically. The reason for this is the frequent occurrence of enterobacteria that are resistant to antibiotics from the carbapenem group. CRE (carbapenem-resistant enterobacteria) are mainly found 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 consisting of chemically branched cyclic decapeptides.
Pharmacologic action
Colistin, more specifically colistimethate sodium (CMS), is a prodrug. Prodrugs are inactive or only slightly pharmacologically active substances that are converted into an active drug only after metabolization in the organism. This process is also called metabolization. The prodrug becomes a metabolite. The prodrug concept is intended to improve the pharmacokinetic substance properties of the drug. Thus, prodrugs often improve bioavailability and reduce the first-pass effect. Colistin is administered parenterally, i.e., bypassing the gastrointestinal tract. After parenteral administration, the inactive ingredient colistimethate sodium is converted to the active colistin base by the chemical process of hydrolysis. This is pharmacologically active. In this process, approximately 33 milligrams of colistin base are formed from 80 milligrams of CMS. Colistin ensures increased permeability on the cell walls of the bacteria. This allows various substances to enter the bacterial cell. Osmolarity is disturbed and eventually the bacterial cells burst. Since Gram-positive bacteria, unlike Gram-negative ones, do not have an outer cell membrane, colistin is only effective on Gram-negative bacteria. Sensitive to colistin are Shigella, Salmonella, Haemophilus influenzae, Acinetobacter, and Pasteurella. Klebsiellae, Escherichia coli, Enterobacter, and Pseudomonas aeruginosa are also usually sensitive to the antibiotic. Proteus, gonococci, gram-positive bacteria, and meningococci, on the other hand, are resistant.
Medical application and use
Colistin is used today only after careful risk-benefit consideration. One indication is patients with cystic fibrosis who suffer from infection with Pseudomonas aeruginosa. Cystic fibrosis is a hereditary disease associated with the production of viscous secretions by the exocrine glands. Affected individuals suffer from chronic respiratory inflammation and gastrointestinal symptoms. Pseudomonas aeruginosa causes pneumonia in patients with a suppressed immune system and compromised airways. These pneumonias are particularly common in cystic fibrosis patients or in patients who are in intensive care. Furthermore, colistin is used to treat infections with the multidrug-resistant bacterium Acinetobacter baumannii. Acinetobacter baumanii is a human pathogenic short-rod bacterium belonging to the Moraxellaceae family. The germ causes nosocomial infections worldwide. Nosocomial infections are infections that are causally related to hospitalizations. Infections with Acinetobacter baumanii are observed primarily in ventilator patients in the intensive care setting. Infection usually results in nosocomial pneumonia. Urinary tract infections, wound infections, and sepsis are also caused by the resistant pathogen.
Risks and side effects
Adverse effects may occur when colistin is taken. Allergic skin reactions or contact dermatitis are common.Allergic asthma attacks are also observed as a reaction to colistin. The antibiotic is also nephrotoxic. In other words, it has a damaging effect on the kidneys. Acute necrosis of the small urinary tubules in the kidney can occur. This usually leads to acute kidney failure within a short time. The kidney can no longer perform its filtration task, so that urinary substances accumulate in the blood. Colistin is not only nephrotoxic, but also neurotoxic. Possible symptoms of damage to the nervous system include dizziness, convulsions, coma, visual disturbances or speech disorders. Blood damage can also be caused by the antibiotic. Colistin should not be used in patients with renal insufficiency due to its nephrotoxic effects. Severe cardiac excretory disorders are also a contraindication. Hypersensitivity to the active ingredient colistin or to other polymyxins is also an exclusion criterion. Because of the severe potential side effects to the unborn or newborn, colistin should not be administered during pregnancy or while breastfeeding. It should be noted that side effects are increased when combined with nephrotoxic agents. Such nephrotoxic drugs include vancomycin, loop diuretics, and aminoglycosides. Agents with neuromuscular blockades, such as muscle relaxants, may also increase the side effects of colistin.
