A typical clinical and pharmacological article
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
Combined drug.
Piperacillin is a bactericidal semisynthetic broad-spectrum antibiotic that inhibits the synthesis of the cell wall of microorganisms.
Tazobactam is an inhibitor of beta-lactamases (including plasmid and chromosomal), which are often the cause of resistance to penicillins and cephalosporins (including cephalosporins of the third generation). The presence of tazobactam greatly expands the spectrum of action of piperacillin.
Most strains of microorganisms resistant to piperacillin and producing beta-lactamases are sensitive to the drug.
It is active against gram-negative aerobic bacteria : Escherichia coli, Salmonella spp., Shigella spp., Citrobacter spp. (including Citrobacter freundii, Citrobacter diversus), Klebsiella spp. (including Klebsiella oxytoca, Klebsiella pneumoniae), Morganella morganii, Moraxella spp. (including Moraxella catarrhalis), Proteus spp.(including Proteus mirabilis, Proteus vulgaris), Pseudomonas aeruginosa (only piperacillin-sensitive strains) and other Pseudomonas spp. (including Burkholderia cepacia, Pseudomonas fluorescens), Neisseria spp. (including Neisseria meningitidis, Neisseria gonorrhoeae), Haemophilus spp. (including Haemophilus influenzae, Haemophilus parainfluenzae), Serratia spp. (including Serratia marcescens, Serratia liquifaciens), Pasteurella multocida, Yersinia spp., Campylobacter spp., Gardnerella vaginalis, Enterobacter spp. (including Enterobacter cloacae, Enterobacter aerogenes), Providencia spp, Stenotrophomonas maltophilia, Acinetobacter spp. (producing and non-producing chromosomal beta-lactamase); Gram-negative anaerobic bacteria : Bacteroides spp. (Bacteroides fragilis, Bacteroides disiens, Bacteroides capillosus, Bacteroides melaninogenicus, Bacteroides oralis, Bacteroides distasonis, Bacteroides uniformis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides bivius, bacteroides asaccharolyticus), Fusobacterium nucleatum; Gram-positive aerobic bacteria : Streptococcus spp. (including Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus bovis), Streptococcus group viridans (C and G), Enterococcus spp. (Enterococcus faecalis, Enterococcus faecium), Staphylococcus spp. (Staphylococcus aureus methicillin-susceptible strains, Staphylococcus epidermidis, Staphylococcus saprophyticus), Listeria monocytogenes, Nocardia spp .; Gram-positive anaerobic bacteria : Clostridium spp. (including Clostridium perfringens, Clostridium difficile), Peptostreptococcus spp., Eubacter spp .; Veillonella spp., Actinomyces spp.
PHARMACOKINETICS
Suction
C max piperacillin after iv infusion of 2.25 or 4.5 g within 30 minutes is reached immediately after its termination and is 134 and 298 Ојg / ml, respectively; the corresponding mean plasma concentrations of 15, 24 and 34 Ојg / ml (plasma piperazillin concentrations after administration in combination with tazobactam are similar to those for administration of equivalent doses of piperacillin mono). The corresponding average maximum plasma concentrations of tazobactam are 15 and 34 Ојg / ml, respectively.
Distribution
The connection with the proteins of the plasma of piperacillin and tazobactam is about 30% (the metabolite of tazobactam practically does not bind to proteins).Piperacillin and tazobactam penetrate well into the tissues and body fluids, including the intestinal mucosa, gallbladder, lungs, bile, bone and tissues of the female reproductive system (uterus, ovaries and fallopian tubes). Average concentrations in tissues - from 50 to 100% of those in the plasma. Virtually does not penetrate through intact GEB.
Excreted in breast milk.
Metabolism
Piperacillin is metabolized to a weakly active desethylate metabolite, tazobactam is metabolized to an inactive metabolite.
Excretion
Excreted by the kidneys through glomerular filtration and tubular secretion: piperacillin - 68% unchanged, tazobactam - 80% unchanged and a small amount - in the form of a metabolite. Piperacillin, tazobactam and desethyl-piperacillin also excrete with bile.
Tazobactam does not cause significant changes in the pharmacodynamics of piperacillin. Apparently, piperacillin reduces the rate of excretion of tazobactam.
T 1/2 piperacillin and tazobactam are independent of the dose and duration of infusion and are 0.7-1.2 h.
Pharmacokinetics in special clinical cases
T 1/2 piperacillin and tazobactam is prolonged with a decrease in the amount of renal blood flow (creatinine clearance): at TC less than 20 ml / min T 1/2 piperazillin is doubled, tazobactam is 4-fold. Correction of the dosing regimen is necessary when the SC is below 40 ml / min.
By means of hemodialysis, 30-50% of the administered dose of piperacillin and tazobactam and an additional 5% in the form of a metabolite are withdrawn.
With peritoneal dialysis, 6% piperacillin and 21% tazobactam are excreted and an additional 18% is given as a metabolite of tazobactam.
In liver cirrhosis, T 1/2 piperacillin is increased by 25%, tazobactam by 18% (no significant correction of the dosing regimen is required).
INDICATIONS
Bacterial infections caused by sensitive microflora in adults and children over 12 years of age :
- infections of the lower respiratory tract (pneumonia, lung abscess, pleural empyema);
- abdominal infections (peritonitis, pelvioperitonitis, cholangitis, gallbladder empyema, appendicitis (including complicated by abscess or perforation)).
- urinary tract infections, incl. Complicated (pyelonephritis, cystitis, prostatitis, epididymitis, gonorrhea, endometritis, vulvovaginitis, postpartum endometritis and adnexitis);
- infections of bones, joints, including osteomyelitis;
- skin and soft tissue infections (phlegmon, furunculosis, abscess, pyoderma, lymphadenitis, lymphangitis, infected trophic ulcers, infected wounds and burns);
- intra-abdominal infections (including in children older than 2 years);
- bacterial infection in patients with neutropenia (including in children under 12 years of age);
- sepsis;
- meningitis;
- prevention of postoperative infection.
DOSING MODE
In / in slowly struyno (for 3-5 minutes) or drip (for at least 20-30 minutes).
The average daily dose for adults and children over 12 years is 12 g of piperacillin and 1.5 g of tazobactam: 2.25 g (2 g piperacillin and 0.25 g tazobactam) every 6 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) every 8 hours .
In infections caused by Pseudomonas aeruginosa, additional assignment of aminoglycosides is indicated.
In chronic renal failure, daily doses of piperacillin / tazobactam are adjusted depending on the CC: at a CC of 20-80 ml / min - 12 g / 1.5 g / day (4 g / 0.5 g every 8 h), with a CC less than 20 ml / min - 8 g / 1 g / day (4 g / 0.5 g every 12 hours).
For patients on hemodialysis, the maximum dose is 8 g of piperacillin and 1 g of tazobactam. Since during the hemodialysis 30-50% of piperacillin is washed out after 4 hours, 1 extra dose of 2 g piperacillin and 0.25 g of tazobactam should be prescribed after each dialysis session.
The course of treatment - usually 7-10 days, according to the indications can be increased to 14 days.
To prepare a solution for intravenous administration, 0.9% sodium chloride solution, 5% dextrose solution, sterile water d / u are used as solvents. For IV infusion, the contents of the vial containing 2.25 g of the drug are diluted in 10 ml of one of the above solutions. For IV infusion, the contents of the vial containing 2.25 or 4.5 g of the drug are diluted respectively in 10 or 20 ml of 0.9% sodium chloride solution, the resulting solution is further dissolved in 50 ml of one of these solutions, or in a 5% solution of dextrose in water, or in a mixture of 5% dextrose and 0.9% sodium chloride.
SIDE EFFECT
Diarrhea (3.8%), vomiting (0.4%), nausea (0.3%), phlebitis (0.2%), thrombophlebitis (0.3%), skin hyperemia (0.5%), allergic reactions (including urticaria 0.2%, cutaneous itching 0.5%, rash 0.6%), development of superinfection (0.2%).
Less than 0.1% : multiform exudative erythema, maculopapular rash, eczema, myasthenia gravis, hallucinations, decreased blood pressure, myalgia in the thorax, febrile syndrome, facial hyperemia, swelling, fatigue, pain and hyperemia at the injection site, bleeding.
Rarely: pseudomembranous colitis.
On the part of laboratory indicators: transient leukopenia, eosinophilia, thrombocytopenia (less frequent than with piperacillin alone), a positive Coombs reaction, hypokalemia, a transient increase in hepatic transaminase and alkaline phosphatase, bilirubin, rarely an increase in urea and creatinine.
CONTRAINDICATIONS
- hypersensitivity (including penicillins, cephalosporins, other inhibitors of beta-lactam antibiotics);
- Children's age (up to 2 years).
C with caution: severe bleeding (including in anamnesis), cystic fibrosis (increased risk of hyperthermia and skin rash), pseudomembranous colitis, chronic renal failure, pregnancy, lactation.
PREGNANCY AND LACTATION
With caution: pregnancy, lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution: CRF. In chronic renal failure, daily doses of piperacillin / tazobactam are adjusted depending on the CK.
APPLICATION FOR CHILDREN
Contraindication - children's age (up to 2 years).
SPECIAL INSTRUCTIONS
Piperacillin + tazobactam has better tolerability and less toxicity compared to ticarcillin, azlocillin and carbenicillin.
In patients who are hypersensitive to penicillins, there may be cross-allergic reactions with other beta-lactam antibiotics.
Safety and efficacy in children under 2 years of age are not defined.
In the case of severe persistent diarrhea, the possibility of developing pseudomembranous enterocolitis should be considered. In the event of this complication, it is necessary to cancel the drug and prescribe oral teykoplanin or vancomycin.
With prolonged treatment, it is necessary to periodically monitor the function of the kidneys, liver, blood counts (including the coagulation system).
Short-term use of high doses of antibiotics for the treatment of gonorrhea can mask or delay the symptoms of the incubation period of syphilis, so before starting antibacterial treatment, gonorrhea patients should be screened for syphilis.
OVERDOSE
Symptoms: agitation, convulsions.
Treatment: symptomatic, incl. the appointment of antiepileptic drugs (including diazepam or barbiturates), hemodialysis or peritoneal dialysis.
DRUG INTERACTION
Pharmaceutically (in one syringe) is incompatible with aminoglycosides, Ringer's solution with lactate, blood, blood substitutes or hydrolysates of albumin.
Drugs that block tubular secretion increase T 1/2 and reduce the renal clearance of both piperacillin and tazobactam, while the C max of both drugs in the plasma remains unchanged.
With simultaneous administration with heparin, oral anticoagulants and other drugs acting on the hemostatic system, more frequent monitoring of the blood coagulation system is necessary.
