Teicoplanin

Teicoplanin

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  BByy:: AAllaa’’aa FFaaddhheellHHaassssaann//DDeepptt.. ooff CClliinniiccaall PPhhaarrmmaaccyy ******************************************************************************************************** ********************** It is a glycopeptide antibiotic, produced by fermentation of Actinoplanes teichomyceticus [mixture of glycopeptide components which have the same core glycopeptide structure composed of a linear heptapeptide aglycone, an α-D-mannose and an acetyl–β-D-glucosamine] Mechanism of action It has bactericidal activity; Binds to the terminal D-Ala-D-Ala sequence of peptides forming the bacterial cell wall and, by stearically hindering the transglycosylation reaction, inhibits the formation of peptidoglycan Spectrum of activity It is active against both aerobic and anaerobic Gram-positive bacteria Species usually sensitive (MIC less than or equal to 16 mg/l): Staphyloccocus aureus and coagulase negative staphylococci (sensitive or resistant to methicillin), streptococci, Enterococci, Listeria monocytogenes, micrococci, Eikenella corradens, group JK corynebacteria and Gram-positive anaerobes including Clostridium difficile, and peptococci. Species usually resistant (MIC superior to 16 mg/l): Nocardia, asteroides, Lactobacillus spp, Leucononostoc and all Gram- negative bacteria (since its large Polar molecules thus cannot penetrate the lipid membrane of Gram-negativebacteria)
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  Bactericidal synergy hasbeen demonstrated in vitro with aminoglycosides against group D streptococci and staphylococci. In vitro combinations of teicoplanin with Rifampicin or fluorinated quinolones show primarily additive effects and sometimes synergy Clinical uses & Therapeutic dosage I. [Doses in moderate infection 3 mg/kg while in severe infection 6 mg/kg I.M or I.V q12hr for 3 doses then q24hr] II. In potentially serious Gram-positive infections including those which cannot be treated with other antimicrobial drugs As Septicaemia, endocarditis, intravenous catheter-associated inf. and peritonitis related to continuous ambulatory peritoneal dialysis [10 mg/kg q12hr for 3-5 doses then q24hr] III. Skin and soft tissue infections IV. Urinary tract infections V. Lower respiratory tract infections VI. Joint and bone infections [12 mg/kg q12hr for 3-5 doses then q24hr- associated with high risk fever & rash] VII. For antimicrobial prophylaxis in orthopaedic surgery at risk of Gram-positive infection (MRSA) [Up to 30 min. before procedure as I.V. inj. 400mg”UNLICENSED”or as I.V. Inf.800 mg] VIII. clostridium difficile inf. (oral application not used for systemic inf. because of non significant GIT absorption) [100–200 mg BID for 10–14 days] IX. treat Gram-positive infections in children from the age of 2 months [For severe infections & neutropenic patients rec- ommended dose is 10 mg/kg q12hr for the 1st 3 doses; thereafter 6 mg/kg should be administered each day while recommended dosage regimen for neonates is a loading of 16 mg/kg followed by 8 mg/kg daily]
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  Pharmacokinetic Distribution & halflife: the plasma level profile after intravenous administration indicates a biphasic distribution with a terminal elimination T1/2 of about 150 hr. [It has a longer half-life than vancomycin (159 hr Vs 11 hr)] it rapidly penetrates into tissues, including skin, fat blister exudates, joint fluid, neutrophils (it enhances their bactericidal activity), and bones and reaches the highest concentrations in the kidney, trachea, lungs and adrenals while it does not readily penetrate into the cerebrospinal fluid neither penetrate red blood cells Plasma protein binding: Approximately 90-95% teicoplanin is bound with weak affinity to plasma proteins Elimination: No metabolites of teicoplanin have been identified; more than 97% of the administered teicoplanin is excreted unchanged mainly in the urine. Effectiveness: Therapeutic response shown within 48-72 hours among majority of pt., in endocarditis and Osteomyelitis, treatment for 3 weeks or longer is recommended, though in severe infections, trough serum concentrations should not be less than 10 mg/l. Special considerations For patients with impaired renal function, reduction of dosage is not required until the fourth day of Targocid treatment. [In mild renal insufficiency: creatinine clearance between 40 and 60 ml/min or eGFR 30-80 ml/min/1.73 m2, Targocid dose should be halved, either by administering the initial unit dose every two days, or by administering half of this dose once a day] [In severe renal insufficiency: creatinine clearance less than 40 ml/min-eGFR ˂30 ml/min/1.73 m2 and in haemodialysed patients, Targocid dose should be one third of the normal either by
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  administering the initialunit dose every third day, or by administering one third of this dose once a day. Teicoplanin is not removed by dialysis. In continuous ambulatory peritoneal dialysis: after a single loading IV dose for 400 mg if the patient is febrile, the recommended dosage is 20 mg/l per bag in the first week, 20 mg/l in alternate bags in the second week and 20 mg/l in the overnight dwell bag only during the third week Cautions /Adverse reactions & possible interactions I. It should be administered with caution in pt. known to be hypersensitive to vancomycin since cross hypersensitivity may occur. However, a history of the “Red Man Syndrome” that can occur with vancomycin is not a contraindication to Teicoplanin Reported anaphylactic reactions include anaphylactic shock, rigors, urticaria, angioedema, rare reports of exfoliative dermatitis, toxic epidermal necrolysis, rare cases of erythema multiforme including SJS. & infusion-related events, such as erythema or flushing of the upper body, have been rarely reported II. Eosinophilia, leucopenia, thrombocytopenia, thrombocytosis, neutropenia and rare cases of reversible agranulocytosis have been reported, especially at higher doses than those usually recommended. (It is advisable for periodic hematological studies to be performed during treatment) III. Renal and auditory function tests should be undertaken in the following circumstances: (Prolonged treatment in patients with renal insufficiency/Concurrent and sequential use of other drugs which may have neurotoxic and or nephrotoxic properties as aminoglycosides, cephaloridine, colistin, amphotericin B, cyclosporin, cisplatin, frusemide and ethacrynic acid)
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  IV. Superinfections: theuse of teicoplanin, especially if prolonged, may result in overgrowth of non-susceptible organisms V. It is recommended that Teicoplanin should not be used during confirmed or presumed pregnancy or during lactation unless the potential benefits outweigh any possible risk (preg. category D). There is no information about the excretion of teicoplanin in milk or placental transfer of the drug VI. Other A.R as Gastro-intestinal: nausea, vomiting, diarrhoea/Central nervous system: dizziness, headache VII. Interactions ..Solutions of teicoplanin and aminoglycosides are incompatible when mixed directly and should not be mixed before injection. ..Liver function: increases in serum transaminases and/or serum alkaline phosphatase. ..Renal function: transient elevations of serum creatinine, renal failure.