00:00What is colistin? Properties, pharmacology and indication for colistin.
00:05Interesting about science and medicine prepared by the details of the channel All Scientific.
00:10What is colistin?
00:12Colistin is an antibiotic from the polymyxine group,
00:15used to treat severe infection caused by gram-negative bacteria.
00:20It is also known as polymyxine E.
00:22Colistin belongs to the class of cyclicationic lipopeptide antibiotic
00:27that exhibit pronounced bactericidal activity.
00:32The basic chemical formula of one of the active components, colistin A, is C53, H100, N16, O13.
00:47The colistin molecule has a complex structure, including a cyclic decapeptide ring,
00:52a linear peptide fragment, a hydrophobic fatty acid tail.
00:56The peptide portion contains alpha-gamma-ademanabotenoidic acid residue,
01:03which carries a positive charge.
01:05This makes colistin a polycateonic compound.
01:08This structure makes the molecule amphophilic,
01:11means it contains both hydrophilic and lipophilic regions.
01:17Amphophilicity plays a key role in the antibiotic's ability to interact with bacterial membranes.
01:23Why is colistin metat sodium used?
01:27In medical practice, colistin metat sodium, a prodrigal form of antibiotic, is more commonly used.
01:35After administration, it hydrolyzes and converts into active colistin.
01:39Chemical properties of colistin.
01:42Polycateonic structure.
01:44Colistin has a number of unique chemical properties that determine its biological activity.
01:49Polycateonic structure.
01:51The presence of several amino groups makes the molecule positively charged at physiological pH.
01:57This ensures strong electrostatic interaction with the negatively charged components of the bacterial cells' membranes.
02:04Chemical properties of colistin.
02:06Amphophilicity.
02:07The molecule contains a hydrophilic peptide moiety, a hydrophobic fatty acid tail.
02:13This structure resembles surfactants allowing colistin to act like a biological detergent.
02:20Chemical properties of colistin.
02:22Binning to lipopolysaccharides.
02:24The antibiotic's primary target is lipopolysaccharides LPS.
02:28In the outer membrane of gram-negative bacteria, lipopolysaccharides contain negatively charged polyphosphate groups.
02:35Colistin displaces the stabilizing calcium-magnesium ions that bind LPS molecules together.
02:43This leads to destruction of the membrane structures.
02:47Chemical properties of colistin.
02:49Impaired membrane permeability.
02:51After binding the hydrophobic tail of colistin is inserted into lipid layer.
02:57The membrane becomes unstable leading to.
03:02You only catch release of intracellular metropolites.
03:06Destruction of the cellular structure.
03:09This results in rapid death of the bacterial cell.
03:13Physical properties of colistin.
03:15Colistin is a white or creamy yellowish powder.
03:18Main physical character is high molecular weight, approximately 1,155 deltons.
03:25Good solubity in water, poor solubity in organ and solvent, hygroscopicity, sensitivity to temperature and light.
03:33Colistin solution gradually lowers potency, so they are usually prepared immediately before use.
03:40Similar drugs to colistin.
03:42Colistin belongs to the polymyxine family.
03:44This group includes polymyxine A, polymyxine B, polymyxine C, polymyxine D.
03:49Polymyxine A.
03:50Colistin.
03:51The most widely used are polymyxine B and colistin.
03:54These antibiotics have a similar mechanism of action and a spectrum of activity.
04:00The history of discovery of colistin.
04:02Colistin was discovered in 1147 by a Japanese scientist.
04:09The antibiotic was isolated from the soil bacterium pine bacillus polymyxia colistinus.
04:15In the 1150, the drug was used to treat bacterial infection.
04:22However, its use later declined to the several toxicity.
04:27The decline and revival of colistin.
04:30The main problems were related to nephrotoxicity.
04:33Neurotoxicity.
04:33At the end of the 20th century, interest in colistin declined significantly.
04:40However, since the beginning of the 21th century, the drug has regained popularity to the spread of a multi-drug
04:48resistant bacteria, resistant to most antibiotics.
04:51Today, colistin is considered a last-line antibiotic.
04:58Bacteria, successively, nesensitive to colistin.
05:01Colistin is inactive primarily against gram-negative bacteria with an outer membra.
05:08Successively microorganisms include pseudomonas aeruginosa, acinobacterium baumani, klebsala pneumoni, escherichia coli, enterobacterium, salmonella, shigella.
05:18This bacteria often cause severe hospital-acquired infection, especially in patients in intensive care units.
05:26Colistin-resistant bacteria.
05:28Some bacteria are naturally resistant to colistin.
05:31This include Proteus, Morganella morgani, Serratium, Marchestians, Providentia, Buclorea, Scepacev, Futurmore.
05:42Colistin has virtually no effect on gram-positive bacteria and anaerobic microorganisms.
05:49This is due to the structural features of a cell membra.
05:53Bacteria, characterized by resistant bacteria.
05:57In recent years, colistin-resistant has become a serious medical problem.
06:02The MCR-Gen, in 2015, the MCR-1-Gen, which encoded the enzyme phosphoethanol amyxin transferase, was discovered.
06:15This enzyme modify lipopolysaccharides in the bacterial membrane, reducing the ability of colistin to bind to them.
06:22A unique feature of the MCR-Gen is that it is located on plasmids, allowing it to be transmitted between
06:30bacteria.
06:30Mutation regulatory system during interaction with colistin.
06:35Resistance can also arise due to mutation in the regulatory systems.
06:39PHOP, PHOQ, PMRA, PMRB.
06:44These systems control the synthesis of cells, membranes, components and can alter its structures.
06:51For what disease is colistin used?
06:53Colistin is used to treat severe infection, hospital-acquired pneumonia, sepsis, urinary tract infection, skin and soft tissue infection, meningitis,
07:03respiratory tract infection and cystic fibrosis.
07:07While drug is especially frequently used in intensive care units.
07:12Alternative to colistin.
07:13Alternative antibiotics include carbapenems, aminoglycosides, tajiciclid, phosphomycin, new beta-lactam agent.
07:24However, for infection caused by extremely resistant bacteria, colistin may remain the only effective drug.
07:32Contraindication for colistin.
07:33Colistin is a contraindicator in hypersensitive to polymyxin, severe renal failure, mastenia.
07:41The drug should also be used with caution during pregnancy in patients with neurological disease.
07:50Collistin side effects.
07:52Rush.
07:53Allergic reaction may manifest as skin rash, itching, redness of skin.
07:59Collistin side effects of colistin, intestinal dysbacteriosis.
08:04The antibiotic may disturb a normal intestinal microflora, possible symptoms, diarrhea, dysbiosis, digestive disorders.
08:12Nephrotoxicity and neurotoxicity of colistin.
08:15Colistin can accumulate in renal tubular cells and cause damage.
08:21Neurotoxicity, possible symptoms, disease, weakness, panesthesia, respiratory disease.
08:27Pharmacokinetics.
08:29Introduction of colistin.
08:30Administration.
08:31Colistin can be administrated intravenously, intramuscularly, by inhalation.
08:36Oral use is limited due to poor absorption.
08:41Distribution of colistin in the body.
08:44After administration, the drug is distributed into body tissue.
08:49To lungs, liver, kidneys, muscle.
08:51However, penetration into cerebrospinal fluid is limited.
08:56Excretion of colistin from the body.
08:58The primary route of elimination is through the kidneys.
09:02Colistin in tato sodium is excreted primarily in the urine.
09:06The half-life though is approximately 3-5 hours, but may be prolonged in renal insufficiency.
09:14Dosage forms of colistin.
09:15Colistin is available in the following forms.
09:18Powder for injection solution, inhalation solution, powder for infusion.
09:23The most common form is colistin metat sodium.
09:26Storage of colistin.
09:28The drug should be stored at the temperature not exciting 25 degree Celsius.
09:35In a dry place, protected from the light solution, are recommended to be used within a short time after preparation.
09:42Molecular mechanism of bacterial membrane destruction.
09:46The mechanism of action of colistin has been studied from a long time by microbiologists and biochemists.
09:53It is currently believed that the antibiotic acts through a multi-step mechanism associated with destruction of a cell membrane
10:01destruction of gram-negative bacteria.
10:04Electrostatic interaction of colistin.
10:06The first step is the electrostatic binding of colistin to lipopolysaccharide LPS of the bacterial outer membrane.
10:14Lipopolysaccharides contain negatively charged phosphat groups.
10:17These groups are normally stabilized by the valent cation, calcium, magnesium.
10:21The positively charged amino groups of colistin compete with these ions and displace them from the membrane.
10:30As a result, interactions between lipopolysaccharide molecules are weakened.
10:35Distabilization of the water membrane with colistin.
10:38After the stabilizing ions are displaced, the membrane structure becomes unstable.
10:44The hydrophobic fatty acid tail of colistin is inserted into the lipid layer of the membrane.
10:52This leads to increased membrane permeability, pore formation, impaired cell barrier function.
10:58Damage of the chitoplasmic membrane by colistin.
11:02After disturbing the outer membrane, the antibiotic reaches the inner chitoplasmic membrane.
11:08Here, it acts as detergent.
11:10It disturbs the lipid bilayer.
11:13It causes ion leakage.
11:14It leads to the release of intracellular metabolites.
11:18This results in osmotic imbalance and biological cell death.
11:23Additional effect of colistin.
11:24Modern research has shown that colistin can also cause other effects.
11:30The formation of reactive oxygen spaces.
11:33Disruption of the bacterial respiratory chain.
11:36Inhibition of certain enzymatic processes.
11:39These processes future enhance the bacterial effect of the drug.
11:43The structure of lipopolysaccharides and the role of lipid A.
11:47To understand the mechanism of action of colistin, it is important to examine the structure of lipopolysaccharides, LPS.
11:56Lipopolysaccharides consist of three main components.
11:59Lipid A, core olisaccharide, or antigen.
12:02Lipid A in the hydrophobic portion of the molecule embedded in the membrane lipid layer.
12:11Lipid A is the primary target of colistin.
12:15It contains phosphat groups, phytoacid residue.
12:19The positively charged amino group of colistin bind to phosphat groups of lipid A.
12:23This leads to the disruption of the membrane structure.
12:26Many mechanisms of bacterial resistance to colistin are associated with a modification of lipid A.
12:33Use of colistin in veterinary medicine.
12:35Colistin has been widely used not only in human medicine, but also in veterinary medicine and agriculture.
12:42For many years, the antibiotic has been used to treat infection in farm animals, to prevent disease, and sometimes as
12:50grout promoter.
12:51Colistin was particularly actively used in pig farming, poultry farming.
12:56However, the widespread use of antibiotics has led to the emergence of resistant bacterial strains.
13:04In 2015, the MCR-1 gene associated with resistance to colistin was discovered in China.
13:11This gene was detected in bacteria isolated from animals, meat products, patients.
13:17Following this, many countries began restructing the use of colistin in agriculture.
13:23Modern research on colistin.
13:25Despite its toxicity, colistin remains an important antibiotic.
13:30Therefore, active research is currently underway to reduce the drug's toxicity, improve the pharmacological properties, create new polymyxine derivatives.
13:40New polymyxine derivatives.
13:41Scientists are developing modified polymyxine molecules that have less nephrotoxicity, return antibacterial activity.
13:50Some of these are already undergoing clinical trials.
13:54Combination therapy with colistin.
13:56In modern medicine, colistin is often used in combination with other antibiotics.
14:01The most common combinations are colistin and carbapenems, colistin and tisicicline, colistin and rymphapine.
14:08This therapy allows to increase treatment effectiveness to reduce the risk of resistant development.
14:14Liposomal form of colistin.
14:16One area of research is the development of liposomal formulation of colistin.
14:24Liposomal allows delivering the antibiotic directly to the site of infection, reducing toxicity, increasing drug concentration in the lungs.
14:32This formulation is particularly promising for the treatment of respiratory tract infection.
14:37The importance of colistin in modern medicine.
14:40Colistin plays an important role in the fight against infection caused by multidrug-resistant bacteria.
14:48In recent years, bacteria strain resistant to virtually all antibiotics have become increasingly common.
14:55These pathogens include carbapenem-resistant Klebsiella pneumoniae, multidrug-resistant acinobacteria baumannii,
15:03resistant strain of Pseudomonas aeruginosa.
15:05In such cases, colistin may remain the only effective drug.
15:09Therefore, the all-health organization classify polymyxine as critically important antibiotics.
15:15Thank you for your attention.
15:17This material was prepared by the social page also scientific.
15:20Attention, this material is for information proposed only when observing very unusual symptoms.
15:25It is recommended to consult a doctor.
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