Vancomycin is an antibiotic from the group of tricyclic glycopeptides isolated from Amycolatopsis orientalis . It is at the moment (2018) the least surmountable for superresistant bacteria, the "antibiotic of strategic reserve", the "medicine of last resort".
Vancomycin | |
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Chemical compound | |
IUPAC | (1 S , 2 R , 18 R , 19 R , 22 S , 25 R , 28 R , 40 S ) - 48- {[(2 S , 3 R , 4 S , 5 S , 6 R ) - 3- { [(2 S , 4 S , 5 S , 6 S ) - 4-amino-5-hydroxy-4,6-dimethyloxan-2-yl] oxy} - 4,5-dihydroxy- 6- (hydroxymethyl) oxan- 2 - yl] oxy} - 22- (carbamoylmethyl) - 5.15- dichloro- 2,18,32,35,37-pentahydroxy- 19- [(2 R ) -4-methyl- 2- (methylamino) pentanamido] - 20,23,26,42,44-pentaoxo-7,13-dioxa- 21,24,27,41,43-pentaazaoctacyclo [26.14.2.2 3.6.6.2 14.17 .1 8.12 .1 29, 33 .0 10.25 .0 34.39 ] pentaconta-3,5,8 (48), 9,11,14,16,29 (45), 30,32,34,36,38,46,49- pentadecaene- 40- carboxylic acid |
Gross formula | C 66 H 75 Cl 2 N 9 O 24 |
Molar mass | 1449.3 g / mol |
CAS | |
Pubchem | |
Drugbank | |
Classification | |
ATH | |
Pharmacokinetics | |
Bioavailable | It is extremely small (orally) |
Metabolism | Displayed unchanged |
The period is half out. | 4-11 hours (adults) 6-10 days (adults, patients with impaired renal function) |
Excretion | through the kidneys |
Mode of administration | |
intravenously , orally | |
Content
Pharmacological action
The mechanism of bactericidal action is due to inhibition of cell wall biosynthesis. In addition, vancomycin can alter the permeability of the cell membrane of bacteria and alter the synthesis of RNA. Cross-resistance between vancomycin and antibiotics of other classes is absent. In vitro, Bankers and Agencies, in the area of graft and pathogens, ( Enterococcus faecalis ); Clostridium difficile (including strains that cause pseudomembranous enterocolitis), Corynebacterium diphtheriae . Other microorganisms that are sensitive to vancomycin in vitro include Listeria monocytogenes , genera of the bacteria Lactobacillus , Actinomyces , Clostridium spp. and Bacillus spp. In vitro, some isolated strains of enterococci and staphylococci are resistant to vancomycin. The combination of vancomycin and aminoglycosides possesses in vitro synergism for many strains of Staphylococcus aureus , Streptococcus viridans , Enterococcus spp., Streptococcus spp. (except for those belonging to serogroup D). Vancomycin is inactive in vitro against gram-negative microorganisms , mycobacteria and fungi.
Pharmacokinetics
- Distribution
With repeated on / in the introduction (held infusion for 60 min) vancomycin at a dose of 1 g (15 mg / kg), the average plasma concentration was about 63 mg / l immediately after the end of infusion; 2 hours after the infusions, the average plasma concentration was about 23 mg / l, and after 11 hours - about 8 mg / l. When conducting multiple infusions (within 30 minutes) of the drug at a dose of 500 mg, the average plasma concentration was about 49 mg / l after the completion of the infusions; 2 h after infusions, the average plasma concentration was about 19 mg / l, and after 6 h - about 10 mg / l. Concentrations in plasma after repeated administration are similar to those in plasma upon single administration. Vd ranges from 0.3 to 0.43 l / kg. When the concentration of vancomycin in serum from 10 mg / l to 100 mg / l, the degree of binding to plasma proteins is 55%. After iv administration of vancomycin, hydrochloride is found in pleural, pericardial, ascitic, synovial fluids and in the atrial abdominal tissue, as well as in urine and peritoneal fluid in concentrations that inhibit the growth of microorganisms. Vancomycin slowly penetrates the BBB, with meningitis there is a more rapid penetration of the drug into the cerebrospinal fluid. Vancomycin penetrates the placental barrier and is excreted in breast milk.
- Metabolism and excretion
Vancomycin is practically not metabolized. The average T1 / 2 is 4-6 hours. About 75% of the dose is excreted in the urine by glomerular filtration in the first 24 hours. The average plasma clearance is about 0.058 L / kg / h, and the average renal clearance is about 0.048 L / kg / h. Renal clearance of vancomycin is fairly constant and ensures its elimination by 70-80%.
- Pharmacokinetics in special clinical situations
In case of impaired renal function, vancomycin elimination slows down. The overall systemic and renal clearance of vancomycin can be reduced in the elderly due to a slower glomerular filtration.
Indications
- endocarditis; the drug is effective both in monotherapy and in combination with aminoglycosides for the treatment of endocarditis caused by Streptococcus viridans or Streptococcus bovis. For endocarditis caused by enterococci (eg, E. faecalis), vancomycin is effective only in combination with aminoglycosides. There is evidence that vancomycin is effective in the treatment of endocarditis caused by Corynebacterium diphtheriae . Vancomycin is successfully used in combination with rifampicin, aminoglycosides, or with both antibiotics for early endocarditis caused by Streptococcus epidermidis or Corynebacterium diphtheriae , after valve prosthetics. In some cases, vancomycin is indicated for the prevention of endocarditis;
- sepsis ;
- infections of bones and joints;
- lower respiratory tract infections;
- infections of the skin and soft tissues.
Vancomycin can also be used for infections caused by gram-positive microorganisms with increased sensitivity to penicillins; intolerance or ineffectiveness of other antibiotic therapy (including penicillins or cephalosporins); infections caused by microorganisms sensitive to vancomycin, but resistant to other antimicrobial agents.
Vancomycin as an oral solution is used to treat pseudomembranous colitis .
Dosing regimen
When using the drug Vancomycin, the recommended concentration of the solution should be no more than 5 mg / ml, and the speed of administration should be no more than 10 mg / min. In patients for whom restriction of fluid intake is indicated, a solution with a concentration of up to 10 mg / ml can be applied at an administration rate not exceeding 10 mg / min. The use of such concentrations increases the likelihood of side effects associated with the infusion. For adults, the daily dose of the drug is 2 g IV (500 mg every 6 hours or 1 g every 12 hours). Each dose should be administered at a rate of not more than 10 mg / min and for at least 60 minutes. The patient’s age and obesity may require a change in the recommended dose based on the determination of serum vancomycin concentration. For children, the dose is set at 10 mg / kg and administered intravenously every 6 hours. Each dose should be administered for at least 60 minutes. For newborns, the initial dose is determined at the rate of 15 mg / kg, and then 10 mg / kg every 12 hours during the first week of their life, starting from the second week of life - every 8 hours until they reach the age of one month. Each dose should be administered for at least 60 minutes. In premature babies as a result of reduced kidney function, a significant reduction in the dose of the drug may be required. Patients with impaired renal function need to individually select the dose depending on the level of serum creatinine or creatinine clearance (see table). In the elderly, vancomycin has a lower clearance and a greater volume of distribution. In this group, it is advisable to select the dose on the basis of a regularly controlled concentration of vancomycin in the serum. In case of impaired renal function in elderly people, a significant reduction in the dose of the drug may be required. Table. Doses of vancomycin, depending on creatinine clearance.
Creatinine clearance (ml / min) Dose of vancomycin (mg / 24 h) 100 1545 90 1390 80 1235 70 1080 60 925 50,770 40,620 30,465 20 310 10 155
This table can not be used to determine the dose of the drug in anuria. Such patients should be prescribed an initial dose of 15 mg / kg body weight to quickly create therapeutic serum concentrations of the drug. The dose required to maintain a stable concentration of the drug is 1.9 mg / kg / 24 h. Patients with severe renal insufficiency, it is advisable to introduce maintenance doses of 250-1000 mg once every few days (for CC 10-50 ml / min - 1 g every 3-7 days, less than 10 ml / min - 1 g every 7-14 days). With anuria, a dose of 1 g is recommended every 7-10 days. In case of pseudomembranous colitis caused by Clostridium difficile due to the use of antibiotics, as well as for the treatment of staphylococcal enterocolitis, the drug is administered orally (on / in the introduction of vancomycin has no advantages for the treatment of these diseases). Adults single dose is 0.5 - 2 g; children dose set at 0.04 g / kg body weight. The multiplicity of reception 3-4 times / day. A single dose is diluted in 30 ml of water and taken orally or injected through a probe. To improve the taste of the solution to it, you can add the usual food syrups. The duration of treatment is 7 to 10 days. Vancomycin when taken orally is not effective for other infections.
Terms of preparation of the solution for administration
The solution is prepared immediately before the introduction of the drug. To do this, add the required volume of water for injection to the vial with a dry, sterile powder to obtain a solution with a concentration of 50 mg / ml. The resulting solution is subject to further dilution to a concentration of not more than 5 mg / ml. The required dose of vancomycin diluted in this way should be administered by fractional intravenous infusion for at least 60 minutes. As solvents, you can use 5% dextrose solution for injection or 0.9% sodium chloride solution for injection. Before injection, the prepared solution for parenteral administration should be checked visually, if possible, for the presence of mechanical impurities and discoloration.
Side Effects
Since the cardiovascular system: cardiac arrest, hot flashes, lower blood pressure, shock (these symptoms are mainly associated with rapid infusion of the drug). On the part of the digestive system: nausea, pseudomembranous colitis. On the part of the hematopoietic system: agranulocytosis, eosinophilia, neutropenia, thrombocytopenia. On the part of the urinary system: interstitial nephritis, changes in laboratory parameters of renal function, impaired renal function. Dermatological reactions: exfoliative dermatitis, benign cystic dermatosis, pruritic dermatosis, rash. Allergic reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, vasculitis. From the side of the central nervous system: vertigo, tinnitus, ototoxic effects (transient or permanent). Most cases of ototoxic reactions were observed in patients who received excessive doses of vancomycin, with a hearing loss in history or with simultaneous therapy with other drugs with possible development of ototoxicity, for example, aminoglycosides. Other: chills, drug fever, anaphylactoid reactions. Patients may develop anaphylactoid reactions during or shortly after vancomycin infusion is too rapid. Rapid drug administration can also cause red man syndrome, redness of the upper body, or pain and spasm of the chest and back muscles. After the cessation of infusion, these reactions usually take place within 20 minutes, but sometimes can last up to several hours. Local reactions: tissue necrosis, pain, thrombophlebitis.
Contraindications
- neuritis of the auditory nerve;
- renal failure;
- pregnancy (I term);
- lactation ;
- hypersensitivity to the drug.
With caution prescribed for hearing impairment (including a history ).
- Pregnancy and lactation
The drug is contraindicated for use in the first trimester of pregnancy. Appointment in the II and III trimesters is possible only for health reasons.
Special instructions
Rapid introduction (for example, within a few minutes) of vancomycin may be accompanied by a marked decrease in blood pressure and, in rare cases, cardiac arrest. Vancomycin should be administered as a diluted solution for at least 60 minutes to avoid adverse reactions associated with the infusion. Vancomycin should be prescribed with caution to patients with teicoplanin allergy, as cases of cross-allergy have been reported. With caution used vancomycin in patients with renal insufficiency and in the elderly (over 60 years). In this category of patients, serum concentrations of vancomycin should be determined, since high, persisting for a long time, concentrations of the drug in the blood may increase the risk of the toxic effect of the drug. Maximum concentrations should not exceed 40 μg / ml, and the minimum - 10 μg / ml, concentrations above 80 μg / ml are considered toxic. Diffusion of the drug solution through the vascular wall during the infusion can cause necrosis of the adjacent tissues. Thrombophlebitis may occur, although the likelihood of their development may be reduced due to the slow administration of diluted solutions (2.5-5 g / l) and the alternation of drug administration sites.
- Control of laboratory parameters
During the course in / in the infusion of the drug should regularly monitor the picture of peripheral blood and indicators of renal function.
- Use in pediatrics
In appointing the drug to the newborn, it is desirable to monitor the concentration in the serum.
Overdose
Symptoms: increased severity of side effects. Treatment: corrective therapy aimed at maintaining glomerular filtration. Vancomycin is poorly removed during dialysis. There is evidence that hemofiltration and hemoperfusion through a polysulfone ion exchange resin leads to an increase in vancomycin clearance.
Drug Interactions
With simultaneous intravenous injection of vancomycin and anesthetics, erythema and anaphylactoid reactions were noted, the risk of a decrease in blood pressure or the development of a neuromuscular blockade is possible. The introduction of vancomycin in the form of a 60-minute infusion before the introduction of anesthetic can reduce the likelihood of these reactions. With the simultaneous and / or sequential systemic or topical use of other potentially ototoxic and / or nephrotoxic drugs (aminoglycosides, amphotericin B, acetylsalicylic acid or other salicylates, bacitracin, capreomycin, carmustine, paromomycin, cyclosporin, loop diuretics, polymyxin, citrate, c, 0, 4, 4, 4, 4, 4, 4). ) requires careful monitoring of the possible development of these symptoms. Kolestiramin reduces the activity of vancomycin. Antihistamines, meklozin, phenothiazines, thioksanteny can mask the symptoms of the ototoxic effect of vancomycin (tinnitus, vertigo).
Pharmaceutical Incompatibility
The vancomycin solution has a low pH, which can cause physical or chemical instability when mixed with other solutions. Mixing with alkaline solutions should be avoided. Solutions of vancomycin and beta-lactam antibiotics are physically incompatible when mixed. The probability of precipitation increases with increasing vancomycin concentration. It is necessary to adequately flush the intravenous system between applications of these antibiotics. In addition, it is recommended to reduce the concentration of vancomycin to 5 mg / ml or less.
Storage Terms and Conditions
List B. The drug should be stored in a dry, dark place, out of reach of children at a temperature not higher than 8 ° C. Shelf life - 2 years.