Tekoplanin, also known as Archaeomycin, was first discovered in 1975.It is a vancomycin group glycopeptide antibiotic obtained by fermentation and extraction of specific mobile actinomycetes, and it is an antibiotic mixture composed of many compounds with very similar chemical structure.
Drug name
Tekoplanin
Alias
Peptidomycin
Foreign name
Teicoplanin
Main indications
Gram positive bacteria infection
CAS
61036-62-2
Molecular formula
C88H97Cl2N9O33
molecular weight
one thousand eight hundred and seventy-nine point six six zero zero zero
Tekoplanin, also known as Archaeomycin, was first discovered in 1975.It is a vancomycin group glycopeptide antibiotic obtained by fermentation and extraction of specific mobile actinomycetes, and it is an antibiotic mixture composed of many compounds with very similar chemical structure.Teicoplanin is a new glycopeptide antibiotic similar to vancomycin, and its antibacterial spectrum and activity are similar to vancomycin.The effect on Staphylococcus aureus is stronger than vancomycin, and the adverse reactions are less.This product is sensitive to gram-positive bacteria such as staphylococcus, streptococcus, enterococcus and most anaerobic positive bacteria.It is mainly used clinically for severe infections caused by sensitive bacteria such as Staphylococcus aureus and Streptococcus, such as endocarditis, osteomyelitis, sepsis, and infections of respiratory tract, urinary tract, skin, and soft tissue.Teicoplanin for injection is mainly used in clinical use, which is produced by Sanofi Aventis (trade name: Tagetes). There are also generic drugs in China.
TekoplaninDifferent from vancomycin in structure, fatty acid side chains are added to the peptide skeleton, which improves lipophilicity and makes it easier to penetrate into tissues and cells.Teicoplanin therefore has more advantages than vancomycin in treatment:
(1) It has low side effects, especially low renal toxicity;
(2) It has a much longer half-life than vancomycin, and only needs to be injected once a day;
(3) It has a more convenient route of administration than vancomycin, and can be administered by intravenous injection or intramuscular injection.
(4) The antibacterial activity of teicoplanin in vivo is several times that of vancomycin, which is safe when used in combination with other antibiotics, and has a long post antibiotic effect.
Therefore, teicoplanin is more conducive to outpatient treatment and acceptance by patients.
essential information
Chinese name: Tekoplanin
English name: Telicoplanin
English alias: TEICOPLANIN, JP;8327a; Tagocid; TeicoplaninSodium; Teicoplanin(sterile,non-sterile);
Teicoplanin has the same mechanism as vancomycin, which interferes with the synthesis of a new part of peptidoglycan in bacterial cell wall.This product passes theAmino acid D-alanyl-D-alanineThe effect is achieved by the combination of some components, which "hides" the parts that can normally be recognized by bacterial cell elongation and cross bridging acids.This binding inhibits two aspects: the growth or extension of subunits forming cell wall chains, which will build the final bridge step connecting to the cell wall.Therefore, the integration and firmness of the cell wall are damaged,Bacterial growthStop and die.
Antibacterial spectrum
Teicoplanin has an antibacterial spectrum similar to vancomycin, which is effective for anaerobic and aerobicGram positive bacteriaAll of them have antibacterial activity.Sensitive bacteria include Staphylococcus aureus andCoagulase negative Staphylococcus(including sensitivity to methicillin andDrug resistant bacteria）, Streptococcus, Enterococcus, Listeria monocytogenes, Micrococcus, Corynebacterium of JK group and Gram positive anaerobic bacteria, the latter includes Clostridium difficile and digestive coccus.
Teicoplanin has stronger effect on Staphylococcus aureus than vancomycin, with fewer adverse reactions.
Because of the unique mechanism of teicoplanin, teicoplanin resistant strains are rare.So yespenicillinClass A and cephalosporins, macrolides,tetracyclineAnd chloramphenicol,AminoglycosideGram positive bacteria resistant to rifampicin and rifampicin were still sensitive to teicoplanin.
Pharmacokinetics
1. Absorption: Teicoplanin is not absorbed when taken orally.After intramuscular injectionBioavailability94%.
2. Distribution (serum concentration): after intravenous injectionSerum concentrationIt shows the distribution of two phases (the fast distribution of one phase is followed by the slow distribution of one phase), and its half-life is about 0.3 and 3 hours respectively.The phase distribution follows a slow dischargehalf life70~100 hours.Single dose: The healthy subjects were given 400mg 30min intravenous injection every 12 hours. After 5 consecutive days, the average serum residual concentration after the first and second intravenous injection was 5.6 ± 0.7mg and 9.4 ± 1.5mg/l, respectively.The serum concentrations at the 12th hour after continued intravenous injection were all more than 10mg/l.giveNeutrophilsThe first treatment for the reduced patients was 400mg intravenous injection every 12 hours;The residual concentration 24 hours after the second intravenous injection was 10.8 ± 5.7mg/l.Healthy people were given six intramuscular injections of 200mg each time. The interval between the first three intramuscular injections was 12 hours, and the subsequent three intramuscular injections were once every 24 hours. The residual concentration was 6.1mg/l 24 hours after the last intramuscular injection.
3、serum albuminCombination: withalbumin90~95%.Tissue diffusion: in the steady state, the obvious distribution changes from 0.6 to 1.21/kg.After injection of radiolabeled teicoplanin, the distribution of teicoplanin has a rapid effect on tissues (especially skin and bone).High concentrations were subsequently achieved in the kidneys, bronchi, lungs and adrenal glands.Tekoplanin seems to be able to enterwhite blood cellAnd improve its antibacterial activity.Tekoplanin will not enterred blood cell，cerebrospinal fluidAnd fat.After a single dose of 400 people were given intravenously, the tissue concentration was:Cancellous bone: The concentration after 0.5 and 24 hours of injection was 10.8μG/g and 7.1μg/g。
4、Compact bone: The concentration after 0.5 and 24 hours of injection was 6.1μG/g and 4.9μg/g。
5. Inflammatory synovial fluid: 24 hours after injection in 6 places, the concentrations were 4 and 1.4 mg/l respectively.
6. Lung tissue: the concentrations after 30 and 60 minutes of injection were 7.9 and 4.5 respectivelyμg/g。
7、Pleural fluid: The concentration reached the peak 6 hours after injection, and the average concentration was 2.8 mg/l.
8、Peritoneal fluid: The concentration reached 27.9mg/l one hour after injection.
9. Biotransformation: no teicoplanin metabolites have been identified, and more than 80% of the given amount will be taken from the prototype within 16 daysurineMiddle discharge.
10. Elimination: patients with normal renal function: almost all of the teicoplanin dose prototype given was excreted from the urine.finalElimination half-life70 to 100 hours.renal functionThe t1/2 of normal adults is about 45h~60h, and the time of renal dysfunction is prolonged, and that of anuria patients can be up to 163h.
11. Patients with renal insufficiency: Teicoplanin is eliminated more slowly than patients with normal renal function.It has a final elimination half-life andCreatinine clearanceCorrelation of
12. Elderly: The change eliminated by teicoplanin is just a reflection of age-related decline of renal function.
indication
This product can be used to treat various serious gram-positive bacterial infections, including the inability to use penicillin andcephalosporinOther antibiotics.This product can be used for non usepenicillinClass A and cephalosporin antibiotics treatment or treatment failure with the above antibioticsYan ShengStaphylococcus infection, or staphylococcus infection resistant to other antibiotics.
Teicoplanin has been proven effective against skin and soft tissue infections, urinary tract infections,respiratory tract infection, osteomyelitis, bone and joint infection, septicemia,endocarditis, keep out of bedperitoneal dialysisAssociated peritonitis.This product can also be used for prevention when there are high risk factors of Gram positive bacteria infection in orthopedic surgery.
Usage and dosage
This product canintravenous injectionIt can also be injected intramuscularly.It can be injected intravenously quickly for 3-5 minutes, or intravenous drip slowly for at least 30 minutes.Generally, the drug is given once a day, but twice on the first day.For most patients with infection caused by sensitive bacteria, there will be therapeutic response 48~72 hours after administration.
The length of treatment depends on the type and severity of infection and the patient's clinical response.
Adult dosage: 6mg ～ 7mg/kg per day, twice a day at the beginning, and once a day later.
Moderate infection, such as skin and soft tissue infectionurinary tract infection Respiratory tract infection: load capacity: 400mg on the first day, intravenous injection once.Maintenance dose: 200mg intravenously or intramuscularly, once a day.
Severe infection, such as bone and joint infectionsepticemiaEndocarditis: load capacity: 400mg intravenous injection, once every 12 hours, three times in a row.Maintenance dose: 400mg intravenously or intramuscularly, once a day.
In some clinical situations, such as patients with severe burn infection or staphylococcal endocarditis, the maintenance dose of teicoplanin may reach 12mg/kg.
Medication for children: Gram positive bacteria infection in children more than 2 months old: the recommended dose for children with severe infection and neutropenia is 10mg/kg, the first three doses are given intravenously every 12 hours, and the subsequent dose is 10mg/kg, intravenously or intramuscularly, once a day.For moderate infection, the recommended dose is 10mg/kg. The first three doses are given intravenously once every 12 hours, followed by 6mg/kg, intravenously or intramuscularly, once a day.The intravenous drip time shall not be less than 30 minutes.
Newborn: the load is 16mg/kg on the first day, only one dose is used, and 8mg/kg is kept for the following days, once a day, and the intravenous drip time is not less than 30 minutes.
Adults and elderly with renal insufficiency: patients with renal impairment still use the conventional dosage for the first three days, and the treatment dosage will be adjusted according to the blood concentration measurement results from the fourth day.Dosage on the 4th day of treatment: mildrenal functionFor incomplete patients (creatinine clearance rate is 40-60mL/min), the dose shall be halved by routine dose once every other day;Or the dosage is halved, once a day.For patients with severe renal insufficiency (creatinine clearance rate less than 40mL/min or hemodialysis patients), the dose is one third of the conventional dose.The drug is administered at the regular dose once every three days;Or 1/3 of the conventional dose, once a day.This product cannot beHemodialysiseliminate.
Continuous non bedriddenperitoneal dialysisSubjects: fever patients, the first loading dose of 400mg is given intravenously, then the dose of 20mg/L is recommended to be given in each dialysis fluid bag in the first week, and only 20mg/L is given in the dialysis fluid bag at night in the third week.The standard dose of 200mg and 400mg of this product is equivalent to the average dose of 3mg/kg and 6mg/kg respectively.If the patient's weight exceeds 85kg, it is recommended to use the same treatment scheme according to kg weight: 3mg/kg for moderate infection and 6mg/kg for severe infection.This medicine can be injected intravenously or intramuscularly, fastintravenous injectionThe time shall not be less than 1 minute, and the time of slow intravenous drip shall not be less than 30 minutes.
Orthopaedic surgery to prevent infection: single dose intravenous injection of 400mg during anesthesia induction period.
Unless there is renal damage, the elderly patients do not need to adjust the dose, see Usage and Dosage.
Adverse reactions
Teicoplanin is well tolerated. The adverse reactions are generally mild and transient, rarely requiring interruption of treatment, and serious adverse reactions are rare.
The following adverse reactions have been reported:
1. Local reaction: erythema, local painThrombophlebitis, which may cause some abscesses after intramuscular injection.
2. Allergic reaction: rash, itching, fever, rigidityBronchospasm, allergic reaction, anaphylactic shock, urticaria, angioneurotic edema, exfoliative dermatitis, toxic epidermal lysis and necrosisErythema multiforme, including Stevens johnson syndrome.
3. In addition, it is rarely reported that infusion related events, such as erythema or upper body, may occur during infusion in patients without previous teicoplanin exposure historyFlush。This kind of event reduces the infusion rate and/or gastrointestinal symptoms: nausea, vomiting, diarrhea. Hematology: Sensibly reversibleGranulocyteLackwhite blood cellReduction, neutropenia, thrombocytopeniaEosinophilsIncrease.
8. Others:Double infection(Over growth of insensitive bacteria).
taboo
People with a history of allergy to teicoplanin cannot use this product.
matters needing attention
Do not use teicoplanin if you have a history of allergy.Pregnant and lactating women, children, severerenal functionUse with caution for incomplete patients.commonlyperitoneal dialysisIt does not affect the discharge of the product.This medicine andvancomycinThere may be cross allergic reaction, so people who are allergic to vancomycin should use it with caution, but those who have ever had "red man syndrome" with vancomycin are not contraindications of this product.It was previously reported that teicoplanin caused thrombocytopenia, especially those whose dosage was higher than the commonly used dosage, it was recommended that blood tests should be performed twice during treatment, and liver and kidney functions should be tested.Tekoplanin once talked about listeningHematology, hepatotoxicity and nephrotoxicity.
Hearing, hematology, liver and kidney functions should be tested in the following cases: patients with renal insufficiency should be treated with this drug for a long time, and other drugs that may have auditory neurotoxicity and/or nephrotoxicity, such as aminoglycosides, should be used simultaneously and successively during the use of this drug,Polymyxin，Amphotericin B, cyclosporin,Cisplatin，FurosemideAnd etanilic acid.However, when the above drugs are used in combination with this drug, there is no evidence of synergistic toxicity.
Monitoring the blood concentration of teicoplanin can improve the treatment. When treating severe infection, the blood concentration of this product should not be less than 10mg/L.
renal functionThe injured person should adjust the dose (see Dose).The use of teicoplanin, especially long-term use, may lead to excessive growth of insensitive bacteria when used in combination with other antibiotics,.If it occurs during treatmentDouble infection, appropriate adjustments should be made.
Women's medication
Pregnant women and breast-feeding women use the drug, although animal reproductive experiments do not show that this product has teratogenic effect.This product should not be used for women whose pregnancy has been confirmed or may be pregnant, unless the doctor believes that it is still necessary to use it despite the danger.There is no data proving that this product is discharged from the breast or enters the placenta.
Children's medication
Teicoplanin can be used to treat gram-positive bacterial infections in children over 2 months old.
Medication for the elderly
Unless there is renal damage, the elderly patients do not need to adjust the dose, see Usage and Dosage.
Drug evaluation
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Treatment of G+bacteria infection
Tekoplanin isActinomyces mobilisIt is a kind of glycopeptide antibiotic produced by fermentation. It can be used to treat gram-positive (G+) bacteria, including aerobic bacteria andAnaerobic bacteriaIt has good antibacterial activity.Its basic chemical structure is similar to vancomycin, but its lipophilicity is strong, and it is easy to penetrate into tissues and cells, leading to bacterial death by blocking the biosynthesis of cell wall.The natural antibacterial spectrum of the drug is aerobic and anaerobic G+bacteria, especially forMethicillinDrug resistant Staphylococcus aureus (MRSA) and Enterococcus have strong antibacterial activity.Because of its high protein binding rate and long half-life, tekoplanin can be administered intravenously or intramuscularly once a day, which is easy to use and has few adverse reactions.It is reported that teicoplanin 200-400mg, once a day, is used alone to treat the patients caused by staphylococcus aureus and enterococcuslower respiratory tract infection, the effective rate is 91%~93%vancomycinEquivalent.There are also research reports that teicoplanin also shows superior clinical efficacy on bacteremia and staphylococcal endocarditis, especially for enterococci with high bactericidal activity and better efficacy, and candidaDouble infectionThe rate was lower than that of the control group.
The adverse reactions of teicoplanin mainly include elevation of liver transaminase, rashGranulocyteReduction and gastrointestinal reactions, ear and kidney toxicity are rare.Although glycopeptide antibiotics have always been effective drugs for the treatment of G+bacteria infection, the infection of glycopeptide moderately sensitive staphylococcus aureus (GISA), vancomycin resistant enterococci (VRE), multidrug resistant streptococcus pneumoniae (DRSP) and other infections are on the increase. Therefore, alternative drugs or combination drugs are needed to more effectively control the infection of GISA, VRE and DRSP.However, the increase of adverse reactions in combination medication is its main disadvantage, especiallyNephrotoxicityAnd increased neurotoxicity.When used in combination with aminoglycosides, teicoplanin is superior to other drugsGlycopeptide antibioticsThe effect on renal function is much smaller, and it rarely causes the allergic reaction "red man syndrome" caused by glycopeptide antibiotics.
Sun Yat-sen UniversityThe Third Affiliated HospitalZhang TianTuo et al. evaluated the efficacy and safety of teicoplanin in the treatment of G+bacteria infection, using randomized controlled and open trials, and vancomycin as a control.60 cases were completed, including 30 cases in the test group, teicoplanin 0.2-0.4g, once a day, intravenous drip;In the control group, 30 patients received intravenous drip of 0.5 g vancomycin three times a day.The course of treatment was 7-14 days.The results showed that the cure rate, effective rate and bacterial clearance rate of the test group were 50%, 80% and 83.3% respectively, while those of the control group were 46.7%, 76.7% and 76.7% respectively. There was no significant difference between the two groups.The incidence of adverse reactions was 10% and 13.3% respectively, and there was no significant difference between the two groups.Therefore, teicoplanin is safe and effective in the treatment of G+bacteria infection.
Because the infectious diseases caused by G+bacteria have a significant upward trend, and the increasingly serious drug resistance of G+bacteria has attracted extensive attention in clinical practice. For example, MRSA has drug resistance to methicillin, accompanied by drug resistance to almost all antibiotics to varying degrees, making treatment difficult and mortality increased.Glycopeptide antibioticsGram positive bacteriaIt has good antibacterial activity. Therefore, teicoplanin is recommended for the treatment of moderate and severe G+bacterial infectious diseases, which is worth popularizing.[2]
