What Is Polymyxin B?

Polymyxin B is an antibiotic. It can inhibit a variety of negative bacteria such as Pseudomonas aeruginosa, E. coli, Klebsiella and Haemophilus, and it is also sensitive to other antibiotic resistant strains. However, due to its severe nephrotoxicity and nerve block effect, it is only used for short-term rescue in burns with sepsis, or for topical spray irrigation. This medicine should not be given intravenously to avoid respiratory failure. The medicine can be formulated into a solution for external use with physiological saline. ^[1]

Chinese name: Polymyxin B
English name: Polymyxin B

nickname: Aerosporin
Application: Resists severe burn infections
Security description: Damage to the liver

Polymyxin B Basic Information

Chinese name: Polymyxin B

Chinese alias: Aerosporin; Arodosin, Polymyxin B; Arudol, Polymyxin B

English name: polymyxin B

English alias: Aerosporin; Polimixina B; Polimixina B [INN-Spanish]; Polymixin B; Polymyxine B; Polymyxine B [INN-French]; Polymyxinum B; Polymyxinum B [INN-Latin]; UNII-J2VZ07J96K

CAS number: 1404-26-8

EINECS number: 215-768-4

Molecular formula: C ₄₃ H ₈₂ N ₁₆ O ₁₂

Molecular weight: 1189.45000

Exact mass: 1188.73000

PSA: 490.66000

LogP: 1.73180

Boiling point: 1651 ° C at 760 mmHg

Flash point: 952.3 ^[2]

B Polymyxin B Polymyxin B Sulfate Related Information

Polymyxin B sulfate (Polymyxin B) English name: Polymyxin B Sulfate (Aerosporin) Polymyxin is a group of polypeptide antibiotics produced by Bacillus polymyxa. Polymyxins b and e are used medicinally. Its sulfate is commonly used as a white crystalline powder, easily soluble in water, and hygroscopic. Stable in acidic solution, neutral solution does not affect titer when stored at room temperature for one week, alkaline solution is unstable.

Chinese name: Polymyxin Sulfate B

English name: Polymyxin B Sulfate

Alias name: Polymyxin B sulfate

Molecular formula: C ₅₆ H ₁₀₀ N ₁₆ O ₁₇ S

Molecular weight: 1301.56

Polymyxin B Toxicology Data

Acute toxicity: LD50 of mouse oral cavity: 790mg / kg; LD50 of mouse abdominal cavity: 20500ug / kg; subcutaneous LD50 of mouse: 59500ug / kg; venous LD50 of mouse: 5400ug / kg; venous LDLo of dog: 8mg / kg; LDLo in puppies' brain: 320ug / kg; subcutaneous LD50 in guinea pigs: 58mg / kg; ^[3]

Polymyxin B molecular structure data

1. Molar refractive index: None available

2. Molar volume (cm3 / mol): no available

3. Isometric Zhang Rong (90.2K): No available

4. Surface tension (dyne / cm): None available

5. Dielectric Constant: None available

6. Polarizability (10-24cm3): None available

7. Mass of single isotope: 1300.717306 Da

8. Nominal mass: 1300 Da

9. Average mass: 1301.5552 Da

Polymyxin B Computational Chemical Data

1. Number of hydrogen-bonded donors: 20

2. Number of hydrogen bond acceptors: 22

3. Number of rotatable chemical bonds: 25

4. Number of tautomers: 1001

5. Topological molecular polar surface area (TPSA): 565

6. Number of heavy atoms: 82

7. Surface charge: 0

8. Complexity: 2010

9. Number of isotope atoms: 0

10. Determine the number of atomic stereocenters: 0

11. Uncertain number of atomic stereocenters: 10

12. Determine the number of chemical bond stereocenters: 0

13. Uncertain number of chemical bond stereocenters: 0

14. Number of covalent bond units: 2 ^[3]

Polymyxin B Properties and Stability

No decomposition if used and stored in accordance with specifications, no known hazardous reactions, avoiding oxides

Polymyxin B storage method

Sealed, stored at 2 ºC -8 ºC

B Polymyxin B Polymyxin B Sulfate Drug Instructions

Product specifications: 500,000 units

Efficacy Indications: resistance to aminoglycosides, third-generation cephalosporins, and severe infections caused by Pseudomonas aeruginosa or other sensitive bacteria, such as bacteremia, endocarditis, pneumonia, and infections after burns.

Chemical composition: <Its antibacterial spectrum and clinical application are similar to polymyxin E. For gram-negative bacilli, [1] [detailed] Its antibacterial spectrum and clinical application are similar to polymyxin E.

Clinical effects of polymyxin B

Its antibacterial spectrum and clinical application are similar to polymyxin E. It inhibits Gram-negative bacilli, such as E. coli, Pseudomonas aeruginosa, Paracoliform, Klebsiella pneumoniae, Acidophilus, Pertussis and Shigella. Or bactericidal effect. Clinically, it is mainly used for infections caused by sensitive bacteria and urinary system infections caused by Pseudomonas aeruginosa, as well as eye, trachea, meningitis, sepsis, burn infections, and skin and mucous membrane infections.

Polymyxin B Pharmacological Action

It has antibacterial effect on Pseudomonas aeruginosa, E. coli, Klebsiella pneumoniae, and gram-negative bacteria such as Haemophilus, Enterobacter, Salmonella, Shigella, Pertussis, Pasteurella and Vibrio. Proteus, Neisseria, Serratia, Pluviden, Gram-positive and obligate anaerobic bacteria are not sensitive to this class of drugs. Bacteria have cross-resistance to this product and polymyxin E, but no cross-resistance has been found between this class of drugs and other antibacterials.

Not absorbed orally. It is mainly excreted by urine after injection, but only a small amount is excreted within 12 hours, and it can reach a concentration of 20 to 100 g / ml in the future. Drug excretion continues within 1 to 3 days after discontinuation.

It is mainly used for wound, urinary tract, eye, ear, trachea and other infections caused by Pseudomonas aeruginosa and other pseudomonas, and can also be used for sepsis and peritonitis.

Polymyxin B usage and dosage

Oral, 100mg ~ 200mg / time for adults, 3 ~ 4times / day; children 10mg ~ 20mg / kg daily, divided into 4 times. Intramuscular or intravenous injection, 50mg 100mg / day for adults, divided into 2 or 3 times; children 1.5mg 2.5mg / kg, divided into 3 ~ 4 times daily.

(1) Intravenous adults and children with normal renal function 1.5 to 2.5 mg / kg (usually no more than 2.5 mg / kg) per day, divided into two, and instilled once every 12 hours. Each 50mg of this product is diluted with 500ml of 5% glucose solution and dripped. Infants with normal renal function can tolerate a dose of 4mg / kg per day.

(2) Intramuscular injection for adults and children at 2.5 to 3 mg / kg per day, dividedly, once every 4 to 6 hours. The daily dose is 4mg / kg for infants and 4.5mg / kg for newborns.

(3) Intrathecal injection (for Pseudomonas aeruginosa meningitis) A 5 mg / ml medicinal solution was prepared with sodium chloride injection. Adults and children over 2 years old, 5 mg daily, after 3 to 4 days of application, changed to once every other day, at least 2 weeks, until the cerebrospinal fluid culture was negative, and the sugar level was normal. For children under 2 years of age, take 2 mg once daily for 3 to 4 days (or 2.5 mg once every other day), and then 2.5 mg once every other day until the test is normal.

(4) The concentration of eye drops is 1 2.5mg / ml.

[Attention points]:

(1) Damage to the kidney is more common, and those with renal insufficiency should be reduced.

(2) Intravenous injection may cause respiratory depression and is generally not used.

(3) The amount of intrathecal injection should not exceed 5mg at a time to prevent irritation of the meninges or nerve tissue.

(4) should not be used in combination with other drugs with renal toxicity or neuromuscular blockade to avoid accidents

Polymyxin B side effects

1 Oral or topical administration has little adverse effects, because it can not be absorbed and has no irritation. Large doses may have gastrointestinal reactions such as nausea, vomiting, and diarrhea.

2 Large doses can cause kidney damage and nervous system dysfunction, such as numbness and edema around the mouth, and severe cases can cause respiratory depression.

[Description of Drugs]: Polymyxin B Sulfate for Injection 50mg per bottle (1mg = 10000 units).

Polymyxin B considerations

(1) Damage to the kidney is more common, and those with renal insufficiency should be reduced.

(2) Intravenous injection may cause respiratory depression and is generally not used.

(3) The amount of intrathecal injection should not exceed 5mg at a time to prevent irritation of the meninges or nerve tissue.

(4) It should not be used in combination with other drugs that have nephrotoxicity or neuromuscular blockade to avoid accidents ^[4] .

Polymyxin B treatment case

Causes of polymyxin B meningitis

Bacterial meningitis is caused by a bacterial infection. Divided into 3 types, namely Haemophilus influenzae type B, Neisseria meningitidis (diplococcus) and Streptococcus pneumoniae (diplococcus pneumoniae). About 80% of the United States is bacterial meningitis. Usually a small number of healthy people carry these bacteria in the nose or on the body without harming the human body. He spreads them by coughing or sneezing. Some studies indicate that people are most susceptible to being infected by a germ when they have a cold, because inflammation of the nose makes it extremely easy for bacteria to enter the skull. Tuberculous meningitis is a non-purulent inflammation of the meninges caused by Mycobacterium tuberculosis, which accounts for about 6% of systemic tuberculosis. After the Mycobacterium tuberculosis infection is disseminated through the blood, it is planted under the pia mater to form tuberculosis nodules. After the nodule ruptures, a large number of tuberculosis bacteria enter the subarachnoid space. In recent years, the incidence and mortality of tuberculous meningitis have increased. Early diagnosis and treatment can improve efficacy and reduce mortality.

Treatment of polymyxin B bacterial meningitis

(1) For the treatment of group B streptococcal meningitis, it is recommended to use penicillin G 500,000 u / kg daily or amikacin 300-400 mg / kg daily, plus 0.75 mg / kg gentamicin daily. Gram-negative bacillus meningitis is more difficult to treat, and the typical medication for amikacin plus an aminoglycoside has a mortality rate of 20% -30%. Third-generation cephalosporins (such as cephalosporin) are the drug of choice for treating proven gram-negative meningitis (or sepsis) or those with affirmative sepsis. The specific clinical situation of meningitis also affects the choice of antibiotics. For example, neonates treated with ampicillin and gentamicin for septicemia within one week after birth, and those who have sepsis and meningitis a few weeks after birth should use vancomycin together. And other different types of aminoglycosides (such as amikacin) or third-generation cephalosporins (such as cephalosporin), polymyxin B and other drugs.

(2) The age of the sick child has some guiding significance in choosing unprepared students. For example, older children suffer less from influenza bacillus meningitis, and most of the newborn brains are drugs for intestinal gram-negative bacilli. It is generally recommended to use general ammonium glycosides glycosides penicillin, because gentamicin and amikacin are effective against intestinal gram-negative bacilli, while penicillin is effective against streptococcus, pneumococcus, and meningococcus. effective. Alternatively, ampicillin, a broad-spectrum antibiotic, can be used instead of penicillin. For resistant strains, benzylpenicillin plus cefotaxime can be used. Chloramphenicol is generally contraindicated in newborns, especially immature infants, because its liver and kidney development is not yet mature, its metabolism and excretory functions are not sound, and it is likely to cause poisoning, manifested as "grey infant syndrome", and even shock death.

(3) To ensure that the drug reaches an effective concentration in the cerebrospinal fluid: firstly, a drug that can easily penetrate the blood-brain barrier should be selected so that the antibiotic concentration in the cerebrospinal fluid exceeds the inhibitory concentration by more than 10 times. And pay attention to the method of administration and dosage. Chloramphenicol, sulfadiazine, and trimethoprim (TMP) can reach the cerebrospinal fluid well and maintain effective antibacterial concentrations. Especially chloramphenicol also passes through the inflamed meninges. Meningeal permeability gradually returns to normal as the condition improves, so the amount of drugs that continue to enter the cerebrospinal fluid also decreases. In order to ensure the therapeutic effect, large doses need to be administered intravenously until the end of the course of treatment. Do not reduce the amount and change the method of administration.

Erythromycin, carbenicillin, vancomycin, 1 ~ 2 generation cephalosporins, aminoglycol antibiotics have a poor ability to cross the blood-brain barrier, and polymyxin B has a better effect at this time. .

(4) If the selected drug can pass the blood-brain barrier well, in principle, no intrathecal injection is needed to avoid adverse reactions and increase the pain of sick children. Drugs such as gentamicin and amikacin cannot easily reach the cerebrospinal fluid. It is administered by intrathecal or intraventricular injection. For infants with late diagnosis and delayed brain diagnosis, pus formation in the appearance of cerebrospinal fluid, or antibiotic resistance to bacteria, the use of intrathecal antibiotics can improve the cure rate. According to the retention time of antibiotics in cerebrospinal fluid, it is injected once a day or every other day, usually 3 to 5 times in a row, until the cerebrospinal fluid becomes clear, the number of cells is significantly reduced, and the bacteria disappear. When glucococcus or rare bacteria are present, or the cerebrospinal fluid is still significantly inflammatory after 3 to 5 times of intrathecal injection, the intrathecal injection time can be extended, and even 7 to 10 times can be given continuously. For intrathecal injection, the drug must be diluted to a certain concentration, and it can be diluted with the extracted cerebrospinal fluid or physiological saline. It should be noted that the amount of injected fluid should be slightly less than the amount of released cerebrospinal fluid. The injection speed should be slow.

Aiming at bacterial meningitis, the use of aminoglycoside drugs or polymyxin B in drug treatment is ideal.