Polymyxin B, sold under the brand name Poly-Rx among others, is an

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

used to treat

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...

pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

, and

urinary tract infections A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidney ...

. While it is useful for many

Gram negative The gram (originally gramme; SI unit symbol g) is a unit of mass in the International System of Units (SI) equal to one one thousandth of a kilogram. Originally defined as of 1795 as "the absolute weight of a volume of pure water equal to th ...

infections, it is not useful for

Gram positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

infections. It can be given by

injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

, or

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...

inhaled Inhalation (or Inspiration) happens when air or other gases enter the lungs. Inhalation of air Inhalation of air, as part of the cycle of breathing, is a vital process for all human life. The process is autonomic (though there are exceptions ...

. The injectable form is generally only used if other options are not available. It is also available as the combinations bacitracin/polymyxin B and neomycin/polymyxin B/bacitracin for use on the skin. Common side effects when given by injection include

kidney problems Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

, neurological problems, fever, itchiness, and rash. Injections into muscle may result in significant pain. Other serious side effects may include

fungal infections Fungal infection, also known as mycosis, is disease caused by fungi. Different types are traditionally divided according to the part of the body affected; superficial, subcutaneous, and systemic. Superficial fungal infections include common ti ...

anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...

, and muscle weakness. It is unclear if use during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

is safe for the baby. Polymyxin B works by breaking down the

cytoplasmic membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

which generally results in bacterial cell death. Polymyxin B was approved for medical use in the United States in 1964. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. In Europe it is only approved to be applied to the skin as of 2015. It is derived from the bacterium ''

Paenibacillus polymyxa ''Paenibacillus polymyxa'', also known as ''Bacillus polymyxa'', is a Gram-positive bacterium capable of fixing nitrogen. It is found in soil, plant tissues, marine sediments and hot springs. It may have a role in forest ecosystems and potentia ...

'' (formerly known as ''

Bacillus polymyxa ''Paenibacillus polymyxa'', also known as ''Bacillus polymyxa'', is a Gram-positive bacterium capable of fixing nitrogen. It is found in soil, plant tissues, marine sediments and hot springs. It may have a role in forest ecosystems and potentia ...

'').

Medical uses

Spectrum of susceptibility

Polymyxin B 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. * ''Haemophilus influenzae'': ≥0.8 μg/ml * ''Pseudomonas aeruginosa'': 0.25 μg/ml – 1 μg/ml

Endotoxin adsorption

An effective use of polymyxin B 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 polymyxin B is bypassed by extracorporeal circulation with perfusion of venous blood through a cartridge on whose fibers polymyxin B 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 polymyxin B (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.

Mechanism of action

#Alters

bacterial outer membrane The bacterial outer membrane is found in gram-negative bacteria. Its composition is distinct from that of the inner cytoplasmic cell membrane - among other things, the outer leaflet of the outer membrane of many gram-negative bacteria includes ...

permeability by binding to a negatively charged site in the lipopolysaccharide layer, which has an electrostatic attraction for the positively charged amino groups in the

cyclic peptide Cyclic peptides are polypeptide chains which contain a circular sequence of bonds. This can be through a connection between the amino and carboxyl ends of the peptide, for example in cyclosporin; a connection between the amino end and a side chai ...

portion (this site normally is a binding site for calcium and magnesium counter ions); the result is a destabilized outer membrane #Fatty acid portion dissolves in hydrophobic region of

and disrupts membrane integrity #Leakage of cellular molecules, inhibition of cellular respiration #Binds and inactivates

endotoxin Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer ...

#Relative absence of selective toxicity: nonspecific for cell membranes of any type, highly toxic. Removal of the hydrophobic tail of polymyxin B 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.

Mixture composition

Polymyxin B 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.

Research application

Polymyxin B 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 Small RNA (sRNA) are polymeric RNA molecules that are less than 200 nucleotides in length, and are usually non-coding Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA ...

(sRNA) responses in ''Salmonella enterica''.

References

External links

* {{Otologicals Polymyxin antibiotics Otologicals Cyclic peptides Polypeptide antibiotics Wikipedia medicine articles ready to translate