Polymyxins are antibiotics used to selectively treat Gram-negative bacterial infections. They work by binding the structure called lipopolysaccharide (LPS), which is present in the outer cell membrane of Gram-negative bacteria. Polymyxins consist of a cyclic peptide which has a long hydrophobic tail, a key in the disruption of the inner and outer cell membranes. Their mechanism of action is similar to that of surfactants or detergents. Increasing antimicrobial resistance, neurotoxicity, and nephrotoxicity make polymyxins last-line agents that are used only when other antibiotics do not work or are contraindicated.
There are different drugs that are classified as polymyxins. Produced by the Gram-positive bacterium called Bacillus polymyxa, these drugs include polymyxin B, polymyxin E or colistin, and polymyxin M or mattacin. Polymyxin B is combined with two other antibiotics called neomycin and bacitracin zinc to make an antimicrobial ophthalmic ointment for the treatment of keratitis, conjunctivitis, keratoconjunctivitis, blepharitis, and blepharoconjunctivitis. This drug is also used as an injection for severe and drug-resistant infections.
Polymyxin E is also used for Gram-negative infections, particularly for multidrug-resistant Acinetobacter and Pseudomonas aeruginosa. The multidrug-resistant Enterobacteriaceae, which has a metallo-beta-lactamase, is also susceptible to polymyxin E. Polymyxin M is a narrow-spectrum antibiotic used to treat gastrointestinal infections such as dysentery and infectious enterocolitis as well as local infections like wound infections, bed sores, necrotic ulcers, and otitis media.
All types of polymyxins are relatively nephrotoxic and neurotoxic, meaning they can damage the kidneys and nerves, which is why they are mostly used as last resort drugs. Neurotoxic reactions include weakness, drowsiness, irritability, paresthesia, numbness, and blurring of vision. Nephrotoxic reactions include cellular casts and albuminuria, or albumin in the urine. Azotemia, or increased levels of nitrogen-containing compounds like urea and creatinine in the blood, may also occur. This is the reason why kidney function monitoring is needed among patients who are using these antibiotics.
When polymyxins are used for extended periods of time, superimposed bacterial or fungal infections may occur, which are called opportunistic infections. One example is candidiasis, caused by Candida albicans. Signs of this type of infection include whitish vaginal discharge or white patches in the oral mucosa.
Polymyxins are poorly absorbed when taken orally. Other routes of administration, such as by intravenous injection or inhalation, are used. Polymyxins are produced by bacteria, thus these drugs can also induce allergic reactions. Symptoms of mild allergy include hives and itching, and severe allergic reactions include dizziness and difficult breathing. If these occur, immediate medical intervention and discontinuation of the drug are needed.