PolymyxinB, sold under the brand name Poly-Rx among others, is an antibiotic used to treat meningitis, pneumonia, sepsis, and urinary tract infections. While it is useful for many Gram negative infections, it is not useful for Gram positive infections. It can be given by injection into a vein, muscle, or cerebrospinal fluid or inhaled. The injectable form is generally only used if other options are not available. It is also available as the combinations bacitracin/âÂÂpolymyxinB and neomycin/âÂÂpolymyxinB/âÂÂbacitracin for use on the skin.
Common side effects when given by injection include kidney problems, neurological problems, fever, itchiness, and rash. Injections into muscle may result in significant pain. Other serious side effects may include fungal infections, anaphylaxis, and muscle weakness. It is unclear if use during pregnancy is safe for the baby. PolymyxinB works by breaking down the cytoplasmic membrane which generally results in bacterial cell death.
PolymyxinB was approved for medical use in the United States in 1964. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In the European Union it is only approved to be applied to the skin as of 2015. It is derived from the bacterium Paenibacillus polymyxa (formerly known as Bacillus polymyxa). In 2023, the combination of polymyxinB with dexamethasone and neomycin was the 260th most commonly prescribed medication in the United States, with more than 1million prescriptions.
PolymyxinB has been used to treat urinary tract infections and meningitis caused by Pseudomonas aeruginosa and Haemophilus influenzae, respectively. The following represents MIC susceptibility data for a few medically significant microorganisms.
An effective use of polymyxinB is found in patients with refractory septic shock, that is, without positive outcome to the administration of standard treatments (increase in volemia and other antibiotics). The obstacle of the toxicity of polymyxinB is bypassed by extracorporeal circulation with perfusion of venous blood through a cartridge on whose fibers polymyxinB is covalently fixed; in this way the antibiotic exerts its bactericidal function but is not released into the blood since it remains fully attached to the fiber. Through this perfusion the cartridge retains the endotoxin, recognized as the trigger of septic shock. The treatment of the cartridge to polymyxinB (Toraymyxin, medical device designed and produced by the Japanese Toray), takes place in two sessions of two hours each, carried out at a distance of 24 hours.
Removal of the hydrophobic tail of polymyxinB yields polymyxin nonapeptide (PMBN), which still binds to LPS, but no longer kills the bacterial cell. However, it still detectably increases the permeability of the bacterial cell wall to other antibiotics, indicating that it still causes some degree of membrane disorganization.
PolymyxinB is composed of polymyxins B1, B1-I, B2, B3, and B6. Polymyxins B1 and B2 are considered major components. These related components are structurally identical with the exception of a variable fatty acid group on each fraction. Results from in vitro studies have shown marginal differences in MIC data when comparing the fractions.
PolymyxinB is also used to induce envelope stress in order to study the organisms' response to such stress. Polymyxin envelope stress assays such as this have been used for the study of small RNA (sRNA) responses in Salmonella enterica.